Artificial cell

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An artificial cell, synthetic cell or minimal cell is an engineered particle that mimics one or many functions of a biological cell. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. [1] As such, liposomes, polymersomes, nanoparticles, microcapsules and a number of other particles can qualify as artificial cells.

Contents

The terms "artificial cell" and "synthetic cell" are used in a variety of different fields and can have different meanings, as it is also reflected in the different sections of this article. Some stricter definitions are based on the assumption that the term "cell" directly relates to biological cells and that these structures therefore have to be alive (or part of a living organism) and, further, that the term "artificial" implies that these structures are artificially built from the bottom-up, i.e. from basic components. As such, in the area of synthetic biology, an artificial cell can be understood as a completely synthetically made cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to replicate. [2] This kind of artificial cell has not yet been made.

However, in other cases, the term "artificial" does not imply that the entire structure is man-made, but instead, it can refer to the idea that certain functions or structures of biological cells can be modified, simplified, replaced or supplemented with a synthetic entity.

In other fields, the term "artificial cell" can refer to any compartment that somewhat resembles a biological cell in size or structure, but is synthetically made, or even fully made from non-biological components. The term "artificial cell" is also used for structures with direct applications such as compartments for drug delivery. Micro-encapsulation allows for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it. [3] [4] The main advantages of encapsulation include improved mimicry in the body, increased solubility of the cargo and decreased immune responses. Notably, artificial cells have been clinically successful in hemoperfusion. [5]

Bottom-up engineering of living artificial cells

Diagram of lipid vesicles showing a solution of biomolecules (green dots) trapped in the vesicle interior. Lipid vesicles.svg
Diagram of lipid vesicles showing a solution of biomolecules (green dots) trapped in the vesicle interior.

The German pathologist Rudolf Virchow brought forward the idea that not only does life arise from cells, but every cell comes from another cell; "Omnis cellula e cellula". [6] Until now, most attempts to create an artificial cell have only created a package that can mimic certain tasks of the cell. Advances in cell-free transcription and translation reactions allow the expression of many genes, but these efforts are far from producing a fully operational cell.

A bottom-up approach to build an artificial cell would involve creating a protocell de novo, entirely from non-living materials. As the term "cell" implies, one prerequisite is the generation of some sort of compartment that defines an individual, cellular unit. Phospholipid membranes are an obvious choice as compartmentalizing boundaries, [7] as they act as selective barriers in all living biological cells. Scientists can encapsulate biomolecules in cell-sized phospholipid vesicles and by doing so, observe these molecules to act similarly as in biological cells and thereby recreate certain cell functions. [8] In a similar way, functional biological building blocks can be encapsulated in these lipid compartments to achieve the synthesis of (however rudimentary) artificial cells.

It is proposed to create a phospholipid bilayer vesicle with DNA capable of self-reproducing using synthetic genetic information. The three primary elements of such artificial cells are the formation of a lipid membrane, DNA and RNA replication through a template process and the harvesting of chemical energy for active transport across the membrane. [9] [10] The main hurdles foreseen and encountered with this proposed protocell are the creation of a minimal synthetic DNA that holds all sufficient information for life, and the reproduction of non-genetic components that are integral in cell development such as molecular self-organization. [11] However, it is hoped that this kind of bottom-up approach would provide insight into the fundamental questions of organizations at the cellular level and the origins of biological life. So far, no completely artificial cell capable of self-reproduction has been synthesized using the molecules of life, and this objective is still in a distant future although various groups are currently working towards this goal. [12]

Another method proposed to create a protocell more closely resembles the conditions believed to have been present during evolution known as the primordial soup. Various RNA polymers could be encapsulated in vesicles and in such small boundary conditions, chemical reactions would be tested for. [13]

Ethics and controversy

Protocell research has created controversy and opposing opinions, including critics of the vague definition of "artificial life". [14] The creation of a basic unit of life is the most pressing ethical concern. [15] The most widespread worry about protocells is their potential threat to human health and the environment through uncontrolled replication. However, artificial cells made through a top-down approach, or any other manipulated forms of existing living cells, are much more likely to be able to exist and reproduce outside of a laboratory and therefore to pose such a threat.

International Research Community

In the mid-2010s the research community started recognising the need to unify the field of synthetic cell research, acknowledging that the task of constructing an entire living organism from non-living components was beyond the resources of a single country. [16]

In 2017 the NSF-funded international Build-a-Cell large-scale research collaboration for the construction of synthetic living cell was started, [17] . Build-a-Cell has conducted nine interdisciplinary workshopping events, open to all interested, to discuss and guide the future of the synthetic cell community. Build-a-Cell was followed by national synthetic cell organizations in several other countries. Those national organizations include FabriCell, [18] MaxSynBio [19] and BaSyC. [20] The European synthetic cell efforts were unified in 2019 as SynCellEU initiative. [21]

Top-down approach to create a minimal living cell

Members from the J. Craig Venter Institute have used a top-down computational approach to knock out genes in a living organism to a minimum set of genes. [22] In 2010, the team succeeded in creating a replicating strain (named Mycoplasma laboratorium) of Mycoplasma mycoides using synthetically created DNA deemed to be the minimum requirement for life which was inserted into a genomically empty bacterium. [22] It is hoped that the process of top-down biosynthesis will enable the insertion of new genes that would perform profitable functions such as generation of hydrogen for fuel or capturing excess carbon dioxide in the atmosphere. [15] The myriad regulatory, metabolic, and signaling networks are not completely characterized. These top-down approaches have limitations for the understanding of fundamental molecular regulation, since the host organisms have a complex and incompletely defined molecular composition. [23] In 2019 a complete computational model of all pathways in Mycoplasma Syn3.0 cell was published, representing the first complete in silico model for a living minimal organism. [24]

Heavy investing in biology has been done by large companies such as ExxonMobil, who has partnered with Synthetic Genomics Inc; Craig Venter's own biosynthetics company in the development of fuel from algae. [25]

As of 2016, Mycoplasma genitalium is the only organism used as a starting point for engineering a minimal cell, since it has the smallest known genome that can be cultivated under laboratory conditions; the wild-type variety has 482, and removing exactly 100 genes deemed non-essential resulted in a viable strain with improved growth rates. Reduced-genome Escherichia coli is considered more useful, and viable strains have been developed with 15% of the genome removed. [26] : 29–30 

A variation of an artificial cell has been created in which a completely synthetic genome was introduced to genomically emptied host cells. [22] Although not completely artificial because the cytoplasmic components as well as the membrane from the host cell are kept, the engineered cell is under control of a synthetic genome and is able to replicate.

Artificial cells for medical applications

Standard artificial cell (top) and drug delivery artificial cell (bottom). Standard and drug delivery artificial cells .png
Standard artificial cell (top) and drug delivery artificial cell (bottom).

History

In the 1960s Thomas Chang developed microcapsules which he would later call "artificial cells", as they were cell-sized compartments made from artificial materials. [27] These cells consisted of ultrathin membranes of nylon, collodion or crosslinked protein whose semipermeable properties allowed diffusion of small molecules in and out of the cell. These cells were micron-sized and contained cells, enzymes, hemoglobin, magnetic materials, adsorbents and proteins. [3]

Later artificial cells have ranged from hundred-micrometer to nanometer dimensions and can carry microorganisms, vaccines, genes, drugs, hormones and peptides. [3] The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal. [28]

In the 1970s, researchers were able to introduce enzymes, proteins and hormones to biodegradable microcapsules, later leading to clinical use in diseases such as Lesch–Nyhan syndrome. [29] Although Chang's initial research focused on artificial red blood cells, only in the mid-1990s were biodegradable artificial red blood cells developed. [30] Artificial cells in biological cell encapsulation were first used in the clinic in 1994 for treatment in a diabetic patient [31] and since then other types of cells such as hepatocytes, adult stem cells and genetically engineered cells have been encapsulated and are under study for use in tissue regeneration. [32] [33]

Materials

Representative types of artificial cell membranes. Artificial cell membranes.png
Representative types of artificial cell membranes.

Membranes for artificial cells can be made of simple polymers, crosslinked proteins, lipid membranes or polymer-lipid complexes. Further, membranes can be engineered to present surface proteins such as albumin, antigens, Na/K-ATPase carriers, or pores such as ion channels. Commonly used materials for the production of membranes include hydrogel polymers such as alginate, cellulose and thermoplastic polymers such as hydroxyethyl methacrylate-methyl methacrylate (HEMA- MMA), polyacrylonitrile-polyvinyl chloride (PAN-PVC), as well as variations of the above-mentioned. [4] The material used determines the permeability of the cell membrane, which for polymer depends on the is important in determining adequate diffusion of nutrients, waste and other critical molecules. Hydrophilic polymers have the potential to be biocompatible and can be fabricated into a variety of forms which include polymer micelles, sol-gel mixtures, physical blends and crosslinked particles and nanoparticles. [4] Of special interest are stimuli-responsive polymers that respond to pH or temperature changes for the use in targeted delivery. These polymers may be administered in the liquid form through a macroscopic injection and solidify or gel in situ because of the difference in pH or temperature. Nanoparticle and liposome preparations are also routinely used for material encapsulation and delivery. A major advantage of liposomes is their ability to fuse to cell and organelle membranes.

Preparation

Many variations for artificial cell preparation and encapsulation have been developed. Typically, vesicles such as a nanoparticle, polymersome or liposome are synthesized. An emulsion is typically made through the use of high pressure equipment such as a high pressure homogenizer or a Microfluidizer. Two micro-encapsulation methods for nitrocellulose are also described below.

High-pressure homogenization

In a high-pressure homogenizer, two liquids in oil/liquid suspension are forced through a small orifice under very high pressure. This process divides the products and allows the creation of extremely fine particles, as small as 1 nm.

Microfluidization

This technique uses a patented Microfluidizer to obtain a greater amount of homogenous suspensions that can create smaller particles than homogenizers. A homogenizer is first used to create a coarse suspension which is then pumped into the microfluidizer under high pressure. The flow is then split into two streams which will react at very high velocities in an interaction chamber until desired particle size is obtained. [34] This technique allows for large scale production of phospholipid liposomes and subsequent material nanoencapsulations.

Drop method

In this method, a cell solution is incorporated dropwise into a collodion solution of cellulose nitrate. As the drop travels through the collodion, it is coated with a membrane thanks to the interfacial polymerization properties of the collodion. The cell later settles into paraffin, where the membrane sets, which is then suspended using a saline solution. The drop method is used for the creation of large artificial cells which encapsulate biological cells, stem cells and genetically engineered stem cells.

Emulsion method

The emulsion method differs in that the material to be encapsulated is usually smaller and is placed in the bottom of a reaction chamber where the collodion is added on top and centrifuged, or otherwise disturbed in order to create an emulsion. The encapsulated material is then dispersed and suspended in saline solution.

Clinical relevance

Drug release and delivery

Artificial cells used for drug delivery differ from other artificial cells since their contents are intended to diffuse out of the membrane, or be engulfed and digested by a host target cell. Often used are submicron, lipid membrane artificial cells that may be referred to as nanocapsules, nanoparticles, polymersomes, or other variations of the term. [35]

Enzyme therapy

Enzyme therapy is being actively studied for genetic metabolic diseases where an enzyme is over-expressed, under-expressed, defective, or not at all there. In the case of under-expression or expression of a defective enzyme, an active form of the enzyme is introduced in the body to compensate for the deficit. On the other hand, an enzymatic over-expression may be counteracted by introduction of a competing non-functional enzyme; that is, an enzyme which metabolizes the substrate into non-active products. When placed within an artificial cell, enzymes can carry out their function for a much longer period compared to free enzymes [3] and can be further optimized by polymer conjugation. [36]

The first enzyme studied under artificial cell encapsulation was asparaginase for the treatment of lymphosarcoma in mice. This treatment delayed the onset and growth of the tumor. [37] These initial findings led to further research in the use of artificial cells for enzyme delivery in tyrosine dependent melanomas. [38] These tumors have a higher dependency on tyrosine than normal cells for growth, and research has shown that lowering systemic levels of tyrosine in mice can inhibit growth of melanomas. [39] The use of artificial cells in the delivery of tyrosinase; and enzyme that digests tyrosine, allows for better enzyme stability and is shown effective in the removal of tyrosine without the severe side-effects associated with tyrosine depravation in the diet. [40]

Artificial cell enzyme therapy is also of interest for the activation of prodrugs such as ifosfamide in certain cancers. Artificial cells encapsulating the cytochrome p450 enzyme which converts this prodrug into the active drug can be tailored to accumulate in the pancreatic carcinoma or implanting the artificial cells close to the tumor site. Here, the local concentration of the activated ifosfamide will be much higher than in the rest of the body thus preventing systemic toxicity. [41] The treatment was successful in animals [42] and showed a doubling in median survivals amongst patients with advanced-stage pancreatic cancer in phase I/II clinical trials, and a tripling in one-year survival rate. [41]

Gene therapy

In treatment of genetic diseases, gene therapy aims to insert, alter or remove genes within an afflicted individual's cells. The technology relies heavily on viral vectors which raises concerns about insertional mutagenesis and systemic immune response that have led to human deaths [43] [44] and development of leukemia [45] [46] in clinical trials. Circumventing the need for vectors by using naked or plasmid DNA as its own delivery system also encounters problems such as low transduction efficiency and poor tissue targeting when given systemically. [4]

Artificial cells have been proposed as a non-viral vector by which genetically modified non-autologous cells are encapsulated and implanted to deliver recombinant proteins in vivo. [47] This type of immuno-isolation has been proven efficient in mice through delivery of artificial cells containing mouse growth hormone which rescued a growth-retardation in mutant mice. [48] A few strategies have advanced to human clinical trials for the treatment of pancreatic cancer, lateral sclerosis and pain control. [4]

Hemoperfusion

The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal. [28] Activated charcoal has the capability of adsorbing many large molecules and has for a long time been known for its ability to remove toxic substances from the blood in accidental poisoning or overdose. However, perfusion through direct charcoal administration is toxic as it leads to embolisms and damage of blood cells followed by removal by platelets. [49] Artificial cells allow toxins to diffuse into the cell while keeping the dangerous cargo within their ultrathin membrane. [28]

Artificial cell hemoperfusion has been proposed as a less costly and more efficient detoxifying option than hemodialysis, [3] in which blood filtering takes place only through size separation by a physical membrane. In hemoperfusion, thousands of adsorbent artificial cells are retained inside a small container through the use of two screens on either end through which patient blood perfuses. As the blood circulates, toxins or drugs diffuse into the cells and are retained by the absorbing material. The membranes of artificial cells are much thinner those used in dialysis and their small size means that they have a high membrane surface area. This means that a portion of cell can have a theoretical mass transfer that is a hundredfold higher than that of a whole artificial kidney machine. [3] The device has been established as a routine clinical method for patients treated for accidental or suicidal poisoning but has also been introduced as therapy in liver failure and kidney failure by carrying out part of the function of these organs. [3] Artificial cell hemoperfusion has also been proposed for use in immunoadsorption through which antibodies can be removed from the body by attaching an immunoadsorbing material such as albumin on the surface of the artificial cells. This principle has been used to remove blood group antibodies from plasma for bone marrow transplantation [50] and for the treatment of hypercholesterolemia through monoclonal antibodies to remove low-density lipoproteins. [51] Hemoperfusion is especially useful in countries with a weak hemodialysis manufacturing industry as the devices tend to be cheaper there and used in kidney failure patients.

Encapsulated cells

Schematic representation of encapsulated cells within artificial membrane. Cell capsule schematic.png
Schematic representation of encapsulated cells within artificial membrane.

The most common method of preparation of artificial cells is through cell encapsulation. Encapsulated cells are typically achieved through the generation of controlled-size droplets from a liquid cell suspension which are then rapidly solidified or gelated to provide added stability. The stabilization may be achieved through a change in temperature or via material crosslinking. [4] The microenvironment that a cell sees changes upon encapsulation. It typically goes from being on a monolayer to a suspension in a polymer scaffold within a polymeric membrane. A drawback of the technique is that encapsulating a cell decreases its viability and ability to proliferate and differentiate. [52] Further, after some time within the microcapsule, cells form clusters that inhibit the exchange of oxygen and metabolic waste, [53] leading to apoptosis and necrosis thus limiting the efficacy of the cells and activating the host's immune system. Artificial cells have been successful for transplanting a number of cells including islets of Langerhans for diabetes treatment, [54] parathyroid cells and adrenal cortex cells.

Encapsulated hepatocytes

Shortage of organ donors make artificial cells key players in alternative therapies for liver failure. The use of artificial cells for hepatocyte transplantation has demonstrated feasibility and efficacy in providing liver function in models of animal liver disease and bioartificial liver devices. [55] Research stemmed off experiments in which the hepatocytes were attached to the surface of a micro-carriers [56] and has evolved into hepatocytes which are encapsulated in a three-dimensional matrix in alginate microdroplets covered by an outer skin of polylysine. A key advantage to this delivery method is the circumvention of immunosuppression therapy for the duration of the treatment. Hepatocyte encapsulations have been proposed for use in a bioartificial liver. The device consists of a cylindrical chamber imbedded with isolated hepatocytes through which patient plasma is circulated extra-corporeally in a type of hemoperfusion. Because microcapsules have a high surface area to volume ratio, they provide large surface for substrate diffusion and can accommodate a large number of hepatocytes. Treatment to induced liver failure mice showed a significant increase in the rate of survival. [55] Artificial liver systems are still in early development but show potential for patients waiting for organ transplant or while a patient's own liver regenerates sufficiently to resume normal function. So far, clinical trials using artificial liver systems and hepatocyte transplantation in end-stage liver diseases have shown improvement of health markers but have not yet improved survival. [57] The short longevity and aggregation of artificial hepatocytes after transplantation are the main obstacles encountered. Hepatocytes co-encapsulated with stem cells show greater viability in culture and after implantation [58] and implantation of artificial stem cells alone have also shown liver regeneration. [59] As such interest has arisen in the use of stem cells for encapsulation in regenerative medicine.

Encapsulated bacterial cells

The oral ingestion of live bacterial cell colonies has been proposed and is currently in therapy for the modulation of intestinal microflora, [60] prevention of diarrheal diseases, [61] treatment of H. Pylori infections, atopic inflammations, [62] lactose intolerance [63] and immune modulation, [64] amongst others. The proposed mechanism of action is not fully understood but is believed to have two main effects. The first is the nutritional effect, in which the bacteria compete with toxin producing bacteria. The second is the sanitary effect, which stimulates resistance to colonization and stimulates immune response. [4] The oral delivery of bacterial cultures is often a problem because they are targeted by the immune system and often destroyed when taken orally. Artificial cells help address these issues by providing mimicry into the body and selective or long term release thus increasing the viability of bacteria reaching the gastrointestinal system. [4] In addition, live bacterial cell encapsulation can be engineered to allow diffusion of small molecules including peptides into the body for therapeutic purposes. [4] Membranes that have proven successful for bacterial delivery include cellulose acetate and variants of alginate. [4] Additional uses that have arosen from encapsulation of bacterial cells include protection against challenge from M. Tuberculosis [65] and upregulation of Ig secreting cells from the immune system. [66] The technology is limited by the risk of systemic infections, adverse metabolic activities and the risk of gene transfer. [4] However, the greater challenge remains the delivery of sufficient viable bacteria to the site of interest. [4]

Artificial blood cells as oxygen carriers

Nano sized oxygen carriers are used as a type of red blood cell substitutes, although they lack other components of red blood cells. They are composed of a synthetic polymersome or an artificial membrane surrounding purified animal, human or recombinant hemoglobin. [67] Overall, hemoglobin delivery continues to be a challenge because it is highly toxic when delivered without any modifications. In some clinical trials, vasopressor effects have been observed. [68] [69]

Artificial red blood cells

Research interest in the use of artificial cells for blood arose after the AIDS scare of the 1980s. Besides bypassing the potential for disease transmission, artificial red blood cells are desired because they eliminate drawbacks associated with allogenic blood transfusions such as blood typing, immune reactions and its short storage life of 42 days. A hemoglobin substitute may be stored at room temperature and not under refrigeration for more than a year. [3] Attempts have been made to develop a complete working red blood cell which comprises carbonic not only an oxygen carrier but also the enzymes associated with the cell. The first attempt was made in 1957 by replacing the red blood cell membrane by an ultrathin polymeric membrane [70] which was followed by encapsulation through a lipid membrane [71] and more recently a biodegradable polymeric membrane. [3] A biological red blood cell membrane including lipids and associated proteins can also be used to encapsulate nanoparticles and increase residence time in vivo by bypassing macrophage uptake and systemic clearance. [72]

Artificial leuko-polymersomes

A leuko-polymersome is a polymersome engineered to have the adhesive properties of a leukocyte. [73] Polymersomes are vesicles composed of a bilayer sheet that can encapsulate many active molecules such as drugs or enzymes. By adding the adhesive properties of a leukocyte to their membranes, they can be made to slow down, or roll along epithelial walls within the quickly flowing circulatory system.

Unconventional types of artificial cells

Electronic artificial cell

The concept of an Electronic Artificial Cell has been expanded in a series of 3 EU projects coordinated by John McCaskill from 2004 to 2015.

The European Commission sponsored the development of the Programmable Artificial Cell Evolution (PACE) program [74] from 2004 to 2008 whose goal was to lay the foundation for the creation of "microscopic self-organizing, self-replicating, and evolvable autonomous entities built from simple organic and inorganic substances that can be genetically programmed to perform specific functions" [74] for the eventual integration into information systems. The PACE project developed the first Omega Machine, a microfluidic life support system for artificial cells that could complement chemically missing functionalities (as originally proposed by Norman Packard, Steen Rasmussen, Mark Beadau and John McCaskill). The ultimate aim was to attain an evolvable hybrid cell in a complex microscale programmable environment. The functions of the Omega Machine could then be removed stepwise, posing a series of solvable evolution challenges to the artificial cell chemistry. The project achieved chemical integration up to the level of pairs of the three core functions of artificial cells (a genetic subsystem, a containment system and a metabolic system), and generated novel spatially resolved programmable microfluidic environments for the integration of containment and genetic amplification. [74] The project led to the creation of the European center for living technology. [75]

Following this research, in 2007, John McCaskill proposed to concentrate on an electronically complemented artificial cell, called the Electronic Chemical Cell. The key idea was to use a massively parallel array of electrodes coupled to locally dedicated electronic circuitry, in a two-dimensional thin film, to complement emerging chemical cellular functionality. Local electronic information defining the electrode switching and sensing circuits could serve as an electronic genome, complementing the molecular sequential information in the emerging protocols. A research proposal was successful with the European Commission and an international team of scientists partially overlapping with the PACE consortium commenced work 2008–2012 on the project Electronic Chemical Cells. The project demonstrated among other things that electronically controlled local transport of specific sequences could be used as an artificial spatial control system for the genetic proliferation of future artificial cells, and that core processes of metabolism could be delivered by suitably coated electrode arrays.

The major limitation of this approach, apart from the initial difficulties in mastering microscale electrochemistry and electrokinetics, is that the electronic system is interconnected as a rigid non-autonomous piece of macroscopic hardware. In 2011, McCaskill proposed to invert the geometry of electronics and chemistry : instead of placing chemicals in an active electronic medium, to place microscopic autonomous electronics in a chemical medium. He organized a project to tackle a third generation of Electronic Artificial Cells at the 100 µm scale that could self-assemble from two half-cells "lablets" to enclose an internal chemical space, and function with the aid of active electronics powered by the medium they are immersed in. Such cells can copy both their electronic and chemical contents and will be capable of evolution within the constraints provided by their special pre-synthesized microscopic building blocks. In September 2012 work commenced on this project. [76]

Artificial neurons

This section is an excerpt from Artificial neuron § Physical artificial cells.[ edit ]

There is research and development into physical artificial neurons – organic and inorganic.

For example, some artificial neurons can receive [77] [78] and release dopamine (chemical signals rather than electrical signals) and communicate with natural rat muscle and brain cells, with potential for use in BCIs/prosthetics. [79] [80]

Low-power biocompatible memristors may enable construction of artificial neurons which function at voltages of biological action potentials and could be used to directly process biosensing signals, for neuromorphic computing and/or direct communication with biological neurons. [81] [82] [83]

Organic neuromorphic circuits made out of polymers, coated with an ion-rich gel to enable a material to carry an electric charge like real neurons, have been built into a robot, enabling it to learn sensorimotorically within the real world, rather than via simulations or virtually. [84] [85] Moreover, artificial spiking neurons made of soft matter (polymers) can operate in biologically relevant environments and enable the synergetic communication between the artificial and biological domains. [86] [87]

Jeewanu

Jeewanu protocells are synthetic chemical particles that possess cell-like structure and seem to have some functional living properties. [88] First synthesized in 1963 from simple minerals and basic organics while exposed to sunlight, it is still reported to have some metabolic capabilities, the presence of semipermeable membrane, amino acids, phospholipids, carbohydrates and RNA-like molecules. [88] However, the nature and properties of the Jeewanu remains to be clarified. [88] [89]

Semi-artificial cyborg cells

This section is an excerpt from Cyborg § Bacterial cyborg cells.[ edit ]
A combination of synthetic biology, nanotechnology and materials science approaches have been used to create a few different iterations of bacterial cyborg cells. [90] [91] [92] These different types of mechanically enhanced bacteria are created with so called bionic manufacturing principles that combine natural cells with abiotic materials. In 2005, researchers from the Department of Chemical Engineering at the University of Nebraska, Lincoln created a super sensitive humidity sensor by coating the bacteria Bacillus cereus with gold nanoparticles, being the first to use a microorganism to make an electronic device and presumably the first cyborg bacteria or cellborg circuit. [93] Researchers from the Department of Chemistry at the University of California, Berkeley published a series of articles in 2016 describing the development of cyborg bacteria capable to harvest sunlight more efficiently than plants. [94] In the first study, the researchers induced the self-photosensitization of a nonphotosynthetic bacterium, Moorella thermoacetica , with cadmium sulfide nanoparticles, enabling the photosynthesis of acetic acid from carbon dioxide. [95] A follow-up article described the elucidation of the mechanism of semiconductor-to-bacterium electron transfer that allows the transformation of carbon dioxide and sunlight into acetic acid. [96] Scientists of the Department of Biomedical Engineering at the University of California, Davis and Academia Sinica in Taiwan, developed a different approach to create cyborg cells by assembling a synthetic hydrogel inside the bacterial cytoplasm of Escherichia. coli cells rendering them incapable of dividing and making them resistant to environmental factors, antibiotics and high oxidative stress. [97] The intracellular infusion of synthetic hydrogel provides these cyborg cells with an artificial cytoskeleton and their acquired tolerance makes them well placed to become a new class of drug-delivery systems positioned between classical synthetic materials and cell-based systems.

See also

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<span class="mw-page-title-main">Polysaccharide</span> Long carbohydrate polymers such as starch, glycogen, cellulose, and chitin

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<span class="mw-page-title-main">Liposome</span> Composite structures made of phospholipids and may contain small amounts of other molecules

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<span class="mw-page-title-main">Dendrimer</span> Highly ordered, branched polymeric molecule

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<span class="mw-page-title-main">Chemotactic drug-targeting</span>

Targeted drug delivery is one of many ways researchers seek to improve drug delivery systems' overall efficacy, safety, and delivery. Within this medical field is a special reversal form of drug delivery called chemotactic drug targeting. By using chemical agents to help guide a drug carrier to a specific location within the body, this innovative approach seeks to improve precision and control during the drug delivery process, decrease the risk of toxicity, and potentially lower the required medical dosage needed. The general components of the conjugates are designed as follows: (i) carrier – regularly possessing promoter effect also on internalization into the cell; (ii) chemotactically active ligands acting on the target cells; (iii) drug to be delivered in a selective way and (iv) spacer sequence which joins drug molecule to the carrier and due to it enzyme labile moiety makes possible the intracellular compartment specific release of the drug. Careful selection of chemotactic component of the ligand not only the chemoattractant character could be expended, however, chemorepellent ligands are also valuable as they are useful to keep away cell populations degrading the conjugate containing the drug. In a larger sense, chemotactic drug-targeting has the potential to improve cancer, inflammation, and arthritis treatment by taking advantage of the difference in environment between the target site and its surroundings. Therefore, this Wikipedia article aims to provide a brief overview of chemotactic drug targeting, the principles behind the approach, possible limitations and advantages, and its application to cancer and inflammation.

<span class="mw-page-title-main">Cell encapsulation</span>

Cell encapsulation is a possible solution to graft rejection in tissue engineering applications. Cell microencapsulation technology involves immobilization of cells within a polymeric semi-permeable membrane. It permits the bidirectional diffusion of molecules such as the influx of oxygen, nutrients, growth factors etc. essential for cell metabolism and the outward diffusion of waste products and therapeutic proteins. At the same time, the semi-permeable nature of the membrane prevents immune cells and antibodies from destroying the encapsulated cells, regarding them as foreign invaders.

<span class="mw-page-title-main">Vectors in gene therapy</span>

Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses and those that use naked DNA or DNA complexes.

A nanocapsule is a nanoscale shell made from a nontoxic polymer. They are vesicular systems made of a polymeric membrane which encapsulates an inner liquid core at the nanoscale. Nanocapsules have many uses, including promising medical applications for drug delivery, food enhancement, nutraceuticals, and for self-healing materials. The benefits of encapsulation methods are for protection of these substances to protect in the adverse environment, for controlled release, and for precision targeting. Nanocapsules can potentially be used as MRI-guided nanorobots or nanobots, although challenges remain.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.

<span class="mw-page-title-main">Polymer-protein hybrid</span> Nanostructures of protein-polymer conjugates

Polymer-protein hybrids are a class of nanostructure composed of protein-polymer conjugates. The protein component generally gives the advantages of biocompatibility and biodegradability, as many proteins are produced naturally by the body and are therefore well tolerated and metabolized. Although proteins are used as targeted therapy drugs, the main limitations—the lack of stability and insufficient circulation times still remain. Therefore, protein-polymer conjugates have been investigated to further enhance pharmacologic behavior and stability. By adjusting the chemical structure of the protein-polymer conjugates, polymer-protein particles with unique structures and functions, such as stimulus responsiveness, enrichment in specific tissue types, and enzyme activity, can be synthesized. Polymer-protein particles have been the focus of much research recently because they possess potential uses including bioseparations, imaging, biosensing, gene and drug delivery.

<span class="mw-page-title-main">Dextran drug delivery systems</span> Polymeric drug carrier

Dextran drug delivery systems involve the use of the natural glucose polymer dextran in applications as a prodrug, nanoparticle, microsphere, micelle, and hydrogel drug carrier in the field of targeted and controlled drug delivery. According to several in vitro and animal research studies, dextran carriers reduce off-site toxicity and improve local drug concentration at the target tissue site. This technology has significant implications as a potential strategy for delivering therapeutics to treat cancer, cardiovascular diseases, pulmonary diseases, bone diseases, liver diseases, colonic diseases, infections, and HIV.

<span class="mw-page-title-main">Intracellular delivery</span> Scientific research area

Intracellular delivery is the process of introducing external materials into living cells. Materials that are delivered into cells include nucleic acids, proteins, peptides, impermeable small molecules, synthetic nanomaterials, organelles, and micron-scale tracers, devices and objects. Such molecules and materials can be used to investigate cellular behavior, engineer cell operations or correct a pathological function.

<span class="mw-page-title-main">Artificial white blood cells</span> Alternative method of immunotherapy

Artificial white blood cells are typically membrane bound vesicles designed to mimic the immunomodulatory behavior of naturally produced leukocytes. While extensive research has been done with regards to artificial red blood cells and platelets for use in emergency blood transfusions, research into artificial white blood cells has been focused on increasing the immunogenic response within a host to treat cancer or deliver drugs in a more favorable fashion. While certain limitations have prevented leukocyte mimicking particles from becoming widely used and FDA approved, more research is being allocated to this area of synthetic blood which has the potential for producing a new form of treatment for cancer and other diseases.

References

  1. ↑ Buddingh' BC, van Hest JC (April 2017). "Artificial Cells: Synthetic Compartments with Life-like Functionality and Adaptivity". Accounts of Chemical Research. 50 (4): 769–777. doi:10.1021/acs.accounts.6b00512. PMC   5397886 . PMID   28094501.
  2. ↑ Deamer D (July 2005). "A giant step towards artificial life?". Trends in Biotechnology. 23 (7): 336–338. doi:10.1016/j.tibtech.2005.05.008. PMID   15935500.
  3. 1 2 3 4 5 6 7 8 9 Chang TM (2007). Artificial cells : biotechnology, nanomedicine, regenerative medicine, blood substitutes, bioencapsulation, cell/stem cell therapy. Hackensack, N.J.: World Scientific. ISBN   978-981-270-576-1.[ page needed ]
  4. 1 2 3 4 5 6 7 8 9 10 11 12 Prakash S (2007). Artificial cells, cell engineering and therapy. Boca Raton, Fl: Woodhead Publishing Limited. ISBN   978-1-84569-036-6.
  5. ↑ Gebelein CG (1983). Polymeric materials and artificial organs based on a symposium sponsored by the Division of Organic Coatings and Plastics Chemistry at the 185th Meeting of the American Chemical Society. Washington, D.C.: American Chemical Society. ISBN   978-0-8412-1084-4.[ page needed ]
  6. ↑ Virchow RL (1858). Die cellularpathologie in ihrer begründung auf physiologische und pathologische gewebelehre [Cellular pathology in its justification of physiological and pathological histology]. Zwanzig Vorlesungen gehalten wahrend der Monate Februar, Marz und April 1858 (in German). Berlin: Verlag von August Hirschwald. p. xv.
  7. ↑ Kamiya K, Takeuchi S (August 2017). "Giant liposome formation toward the synthesis of well-defined artificial cells". Journal of Materials Chemistry B. 5 (30): 5911–5923. doi:10.1039/C7TB01322A. PMID   32264347.
  8. ↑ Litschel T, Schwille P (May 2021). "Protein Reconstitution Inside Giant Unilamellar Vesicles". Annual Review of Biophysics. 50: 525–548. doi:10.1146/annurev-biophys-100620-114132. PMID   33667121. S2CID   232131463.
  9. ↑ Szostak JW, Bartel DP, Luisi PL (January 2001). "Synthesizing life". Nature. 409 (6818): 387–390. doi: 10.1038/35053176 . PMID   11201752. S2CID   4429162.
  10. ↑ Pohorille A, Deamer D (March 2002). "Artificial cells: prospects for biotechnology". Trends in Biotechnology. 20 (3): 123–128. doi:10.1016/S0167-7799(02)01909-1. hdl: 2060/20020043286 . PMID   11841864.
  11. ↑ Noireaux V, Maeda YT, Libchaber A (March 2011). "Development of an artificial cell, from self-organization to computation and self-reproduction". Proceedings of the National Academy of Sciences of the United States of America. 108 (9): 3473–3480. Bibcode:2011PNAS..108.3473N. doi: 10.1073/pnas.1017075108 . PMC   3048108 . PMID   21317359.
  12. ↑ Rasmussen S, Chen L, Nilsson M, Abe S (Summer 2003). "Bridging nonliving and living matter". Artificial Life. 9 (3): 269–316. CiteSeerX   10.1.1.101.1606 . doi:10.1162/106454603322392479. PMID   14556688. S2CID   6076707.
  13. ↑ Gilbert W (20 February 1986). "Origin of life: The RNA world". Nature. 319 (6055): 618. Bibcode:1986Natur.319..618G. doi: 10.1038/319618a0 . S2CID   8026658.
  14. ↑ Bedau M, Church G, Rasmussen S, Caplan A, Benner S, Fussenegger M, et al. (May 2010). "Life after the synthetic cell". Nature. 465 (7297): 422–424. Bibcode:2010Natur.465..422.. doi:10.1038/465422a. PMID   20495545. S2CID   27471255.
  15. 1 2 Parke EC (2009). Beadau MA (ed.). The ethics of protocells moral and social implications of creating life in the laboratory ([Online-Ausg.] ed.). Cambridge, Mass.: MIT Press. ISBN   978-0-262-51269-5.
  16. ↑ Swetlitz, Ike (28 July 2017). "From chemicals to life: Scientists try to build cells from scratch". Stat. Retrieved 4 Dec 2019.
  17. ↑ "Build-a-Cell" . Retrieved 4 Dec 2019.
  18. ↑ "FabriCell" . Retrieved 8 Dec 2019.
  19. ↑ "MaxSynBio - Max Planck Research Network in Synthetic Biology" . Retrieved 8 Dec 2019.
  20. ↑ "BaSyC" . Retrieved 8 Dec 2019.
  21. ↑ "SynCell EU" . Retrieved 8 Dec 2019.
  22. 1 2 3 Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, et al. (July 2010). "Creation of a bacterial cell controlled by a chemically synthesized genome". Science. 329 (5987): 52–56. Bibcode:2010Sci...329...52G. doi:10.1126/science.1190719. PMID   20488990. S2CID   7320517.
  23. ↑ Armstrong R (September 2014). "Designing with protocells: applications of a novel technical platform". Life. 4 (3): 457–490. Bibcode:2014Life....4..457A. doi: 10.3390/life4030457 . PMC   4206855 . PMID   25370381.
  24. ↑ Breuer M, Earnest TM, Merryman C, Wise KS, Sun L, Lynott MR, et al. (January 2019). "Essential metabolism for a minimal cell". eLife. 8. doi: 10.7554/eLife.36842 . PMC   6609329 . PMID   30657448.
  25. ↑ Sheridan C (September 2009). "Big oil bucks for algae". Nature Biotechnology. 27 (9): 783. doi: 10.1038/nbt0909-783 . PMID   19741613. S2CID   205270805.
  26. ↑ EU Directorate-General for Health and Consumers (2016-02-12). Opinion on synthetic biology II: Risk assessment methodologies and safety aspects. Publications Office. doi:10.2772/63529. ISBN   9789279439162.
  27. ↑ Chang TM (October 1964). "Semipermeable Microcapsules". Science. 146 (3643): 524–525. Bibcode:1964Sci...146..524C. doi:10.1126/science.146.3643.524. PMID   14190240. S2CID   40740134.
  28. 1 2 3 Chang TM (1996). "Editorial: past, present and future perspectives on the 40th anniversary of hemoglobin based red blood cell substitutes". Artificial Cells Blood Substit Immobil Biotechnol. 24: ixxxvi. NAID   10005526771.
  29. ↑ Palmour RM, Goodyer P, Reade T, Chang TM (September 1989). "Microencapsulated xanthine oxidase as experimental therapy in Lesch-Nyhan disease". Lancet. 2 (8664): 687–688. doi:10.1016/s0140-6736(89)90939-2. PMID   2570944. S2CID   39716068.
  30. ↑ Chang TM (1997). Blood substitutes. Basel: Karger. ISBN   978-3-8055-6584-4.[ page needed ]
  31. ↑ Soon-Shiong P, Heintz RE, Merideth N, Yao QX, Yao Z, Zheng T, et al. (April 1994). "Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation". Lancet. 343 (8903): 950–951. doi:10.1016/S0140-6736(94)90067-1. PMID   7909011. S2CID   940319.
  32. ↑ Liu ZC, Chang TM (June 2003). "Coencapsulation of hepatocytes and bone marrow stem cells: in vitro conversion of ammonia and in vivo lowering of bilirubin in hyperbilirubemia Gunn rats". The International Journal of Artificial Organs. 26 (6): 491–497. doi:10.1177/039139880302600607. PMID   12894754. S2CID   12447199.
  33. ↑ Aebischer P, Schluep M, Déglon N, Joseph JM, Hirt L, Heyd B, et al. (June 1996). "Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients". Nature Medicine. 2 (6): 696–699. doi:10.1038/nm0696-696. PMID   8640564. S2CID   8049662.
  34. ↑ Vivier A, Vuillemard JC, Ackermann HW, Poncelet D (1992). "Large-scale blood substitute production using a microfluidizer". Biomaterials, Artificial Cells, and Immobilization Biotechnology. 20 (2–4): 377–397. doi:10.3109/10731199209119658. PMID   1391454.
  35. ↑ Jakaria MG, Sorkhdini P, Yang D, Zhou Y, Meenach SA (February 2022). "Lung cell membrane-coated nanoparticles capable of enhanced internalization and translocation in pulmonary epithelial cells". International Journal of Pharmaceutics. 613: 121418. doi:10.1016/j.ijpharm.2021.121418. PMC   8792290 . PMID   34954003.
  36. ↑ Park et al. 1981[ full citation needed ][ page needed ]
  37. ↑ Chang TM (January 1971). "The in vivo effects of semipermeable microcapsules containing L-asparaginase on 6C3HED lymphosarcoma". Nature. 229 (5280): 117–118. Bibcode:1971Natur.229..117C. doi:10.1038/229117a0. PMID   4923094. S2CID   4261902.
  38. ↑ Yu B, Chang TM (April 2004). "Effects of long-term oral administration of polymeric microcapsules containing tyrosinase on maintaining decreased systemic tyrosine levels in rats". Journal of Pharmaceutical Sciences. 93 (4): 831–837. doi:10.1002/jps.10593. PMID   14999721.
  39. ↑ Meadows GG, Pierson HF, Abdallah RM, Desai PR (August 1982). "Dietary influence of tyrosine and phenylalanine on the response of B16 melanoma to carbidopa-levodopa methyl ester chemotherapy". Cancer Research. 42 (8): 3056–3063. PMID   7093952.
  40. ↑ Chang TM (February 2004). "Artificial cell bioencapsulation in macro, micro, nano, and molecular dimensions: keynote lecture". Artificial Cells, Blood Substitutes, and Biotechnology. 32 (1): 1–23. doi:10.1081/bio-120028665. PMID   15027798. S2CID   37799530.
  41. 1 2 Löhr M, Hummel F, Faulmann G, Ringel J, Saller R, Hain J, et al. (May 2002). "Microencapsulated, CYP2B1-transfected cells activating ifosfamide at the site of the tumor: the magic bullets of the 21st century". Cancer Chemotherapy and Pharmacology. 49 (Suppl 1): S21–S24. doi:10.1007/s00280-002-0448-0. PMID   12042985. S2CID   10329480.
  42. ↑ Kröger JC, Benz S, Hoffmeyer A, Bago Z, Bergmeister H, Günzburg WH, et al. (1999). "Intra-arterial instillation of microencapsulated, Ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting". Pancreatology. 3 (1): 55–63. doi:10.1159/000069147. PMID   12649565. S2CID   23711385.
  43. ↑ Carmen IH (April 2001). "A death in the laboratory: the politics of the Gelsinger aftermath". Molecular Therapy. 3 (4): 425–428. doi: 10.1006/mthe.2001.0305 . PMID   11319902.
  44. ↑ Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, et al. (1 September 2003). "Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer". Molecular Genetics and Metabolism. 80 (1–2): 148–158. doi:10.1016/j.ymgme.2003.08.016. PMID   14567964.
  45. ↑ Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, et al. (April 2000). "Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease". Science. 288 (5466): 669–672. Bibcode:2000Sci...288..669C. doi:10.1126/science.288.5466.669. PMID   10784449.
  46. ↑ Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P, et al. (October 2003). "LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1". Science. 302 (5644): 415–419. Bibcode:2003Sci...302..415H. doi:10.1126/science.1088547. PMID   14564000. S2CID   9100335.
  47. ↑ Chang PL, Van Raamsdonk JM, Hortelano G, Barsoum SC, MacDonald NC, Stockley TL (February 1999). "The in vivo delivery of heterologous proteins by microencapsulated recombinant cells". Trends in Biotechnology. 17 (2): 78–83. doi:10.1016/S0167-7799(98)01250-5. PMID   10087608.
  48. ↑ al-Hendy A, Hortelano G, Tannenbaum GS, Chang PL (February 1995). "Correction of the growth defect in dwarf mice with nonautologous microencapsulated myoblasts--an alternate approach to somatic gene therapy". Human Gene Therapy. 6 (2): 165–175. doi:10.1089/hum.1995.6.2-165. PMID   7734517.
  49. ↑ Dunea G, Kolff WJ (1965). "Clinical Experience with the Yatzidis Charcoal Artificial Kidney". Transactions of the American Society for Artificial Internal Organs. 11: 178–182. doi: 10.1097/00002480-196504000-00035 . PMID   14329080.
  50. ↑ Bensinger WI, Buckner CD, Clift RA (1985). "Whole blood immunoadsorption of anti-A or anti-B antibodies". Vox Sanguinis. 48 (6): 357–361. doi:10.1111/j.1423-0410.1985.tb00196.x. PMID   3892895. S2CID   12777645.
  51. ↑ Yang L, Cheng Y, Yan WR, Yu YT (2004). "Extracorporeal whole blood immunoadsorption of autoimmune myasthenia gravis by cellulose tryptophan adsorbent". Artificial Cells, Blood Substitutes, and Biotechnology. 32 (4): 519–528. doi: 10.1081/bio-200039610 . PMID   15974179. S2CID   7269229.
  52. ↑ Chang PL (1994). "Calcium Phosphate-Mediated DNA Transfection". In Wolff JA (ed.). Gene Therapeutics. Boston: Birkhauser. pp. 157–179. doi:10.1007/978-1-4684-6822-9_9. ISBN   978-1-4684-6822-9.
  53. ↑ Ponce S, Orive G, Gascón AR, Hernández RM, Pedraz JL (April 2005). "Microcapsules prepared with different biomaterials to immobilize GDNF secreting 3T3 fibroblasts". International Journal of Pharmaceutics. 293 (1–2): 1–10. doi:10.1016/j.ijpharm.2004.10.028. PMID   15778039.
  54. ↑ Kizilel S, Garfinkel M, Opara E (December 2005). "The bioartificial pancreas: progress and challenges". Diabetes Technology & Therapeutics. 7 (6): 968–985. doi:10.1089/dia.2005.7.968. PMID   16386103.
  55. 1 2 Dixit V, Gitnick G (27 November 2003). "The bioartificial liver: state-of-the-art". The European Journal of Surgery. Supplement. 164 (582): 71–76. doi: 10.1080/11024159850191481 . PMID   10029369.
  56. ↑ Demetriou AA, Whiting JF, Feldman D, Levenson SM, Chowdhury NR, Moscioni AD, et al. (September 1986). "Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes". Science. 233 (4769): 1190–1192. Bibcode:1986Sci...233.1190D. doi:10.1126/science.2426782. PMID   2426782.
  57. ↑ Sgroi A, Serre-Beinier V, Morel P, Bühler L (February 2009). "What clinical alternatives to whole liver transplantation? Current status of artificial devices and hepatocyte transplantation". Transplantation. 87 (4): 457–466. doi: 10.1097/TP.0b013e3181963ad3 . PMID   19307780.
  58. ↑ Liu ZC, Chang TM (March 2002). "Increased viability of transplanted hepatocytes when hepatocytes are co-encapsulated with bone marrow stem cells using a novel method". Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. 30 (2): 99–112. doi: 10.1081/bio-120003191 . PMID   12027231. S2CID   26667880.
  59. ↑ Pedraz JL, Orive G, eds. (2010). Therapeutic applications of cell microencapsulation (Online-Ausg. ed.). New York: Springer Science+Business Media. ISBN   978-1-4419-5785-6.
  60. ↑ Mattila-Sandholm T, Blum S, Collins JK, Crittenden R, De Vos W, Dunne C, et al. (1 December 1999). "Probiotics: towards demonstrating efficacy". Trends in Food Science & Technology. 10 (12): 393–399. doi:10.1016/S0924-2244(00)00029-7.
  61. ↑ Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ (November 2002). "Efficacy of probiotic use in acute diarrhea in children: a meta-analysis". Digestive Diseases and Sciences. 47 (11): 2625–2634. doi:10.1023/A:1020501202369. PMID   12452406. S2CID   207559325.
  62. ↑ Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S (November 2000). "Probiotics in the management of atopic eczema". Clinical and Experimental Allergy. 30 (11): 1604–1610. doi:10.1046/j.1365-2222.2000.00943.x. PMID   11069570. S2CID   13524021.
  63. ↑ Lin MY, Yen CL, Chen SH (January 1998). "Management of lactose maldigestion by consuming milk containing lactobacilli". Digestive Diseases and Sciences. 43 (1): 133–137. doi:10.1023/A:1018840507952. PMID   9508514. S2CID   22890925.
  64. ↑ Gill HS (1 May 1998). "Stimulation of the Immune System by Lactic Cultures". International Dairy Journal. 8 (5–6): 535–544. doi:10.1016/S0958-6946(98)00074-0.
  65. ↑ Aldwell FE, Tucker IG, de Lisle GW, Buddle BM (January 2003). "Oral delivery of Mycobacterium bovis BCG in a lipid formulation induces resistance to pulmonary tuberculosis in mice". Infection and Immunity. 71 (1): 101–108. doi:10.1128/IAI.71.1.101-108.2003. PMC   143408 . PMID   12496154.
  66. ↑ Park JH, Um JI, Lee BJ, Goh JS, Park SY, Kim WS, Kim PH (September 2002). "Encapsulated Bifidobacterium bifidum potentiates intestinal IgA production". Cellular Immunology. 219 (1): 22–27. doi:10.1016/S0008-8749(02)00579-8. PMID   12473264.
  67. ↑ Kim HW, Greenburg AG (September 2004). "Artificial oxygen carriers as red blood cell substitutes: a selected review and current status". Artificial Organs. 28 (9): 813–828. doi:10.1111/j.1525-1594.2004.07345.x. PMID   15320945.
  68. ↑ Nelson DJ (1998). "Blood and HemAssistTM (DCLHb): Potentially a complementary therapeutic team". In Chang TM (ed.). Blood Substitutes: Principles, Methods, Products and Clinical Trials. Vol. 2. Basel: Karger. pp. 39–57.
  69. ↑ Burhop KE, Estep TE (2001). "Hemoglobin induced myocardial lesions". Artificial Cells, Blood Substitutes, and Biotechnology. 29 (2): 101–106. doi:10.1080/10731190108951271. PMC   3555357 .
  70. ↑ "30th Anniversary in Artificial Red Blood Cell Research". Artificial Cells, Blood Substitutes and Biotechnology. 16 (1–3): 1–9. 1 January 1988. doi:10.3109/10731198809132551.
  71. ↑ Djordjevich L, Miller IF (May 1980). "Synthetic erythrocytes from lipid encapsulated hemoglobin". Experimental Hematology. 8 (5): 584–592. PMID   7461058.
  72. ↑ Hu CM, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L (July 2011). "Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform". Proceedings of the National Academy of Sciences of the United States of America. 108 (27): 10980–10985. Bibcode:2011PNAS..10810980H. doi: 10.1073/pnas.1106634108 . PMC   3131364 . PMID   21690347.
  73. ↑ Hammer DA, Robbins GP, Haun JB, Lin JJ, Qi W, Smith LA, et al. (1 January 2008). "Leuko-polymersomes". Faraday Discussions. 139: 129–41, discussion 213–28, 419–20. Bibcode:2008FaDi..139..129H. doi:10.1039/B717821B. PMC   2714229 . PMID   19048993.
  74. 1 2 3 "Programmable Artificial Cell Evolution" (PACE)". PACE Consortium.
  75. ↑ "European center for living technology". European Center for Living Technology. Archived from the original on 2011-12-14.
  76. ↑ "Microscale Chemically Reactive Electronic Agents". Ruhr Universität Bochum.
  77. ↑ Kleiner, Kurt (25 August 2022). "Making computer chips act more like brain cells". Knowable Magazine | Annual Reviews. doi:10.1146/knowable-082422-1 . Retrieved 23 September 2022.
  78. ↑ Keene, Scott T.; Lubrano, Claudia; Kazemzadeh, Setareh; Melianas, Armantas; Tuchman, Yaakov; Polino, Giuseppina; Scognamiglio, Paola; Cinà, Lucio; Salleo, Alberto; van de Burgt, Yoeri; Santoro, Francesca (September 2020). "A biohybrid synapse with neurotransmitter-mediated plasticity". Nature Materials. 19 (9): 969–973. Bibcode:2020NatMa..19..969K. doi:10.1038/s41563-020-0703-y. ISSN   1476-4660. PMID   32541935. S2CID   219691307.
  79. ↑ "Artificial neuron swaps dopamine with rat brain cells like a real one". New Scientist. Retrieved 16 September 2022.
  80. ↑ Wang, Ting; Wang, Ming; Wang, Jianwu; Yang, Le; Ren, Xueyang; Song, Gang; Chen, Shisheng; Yuan, Yuehui; Liu, Ruiqing; Pan, Liang; Li, Zheng; Leow, Wan Ru; Luo, Yifei; Ji, Shaobo; Cui, Zequn; He, Ke; Zhang, Feilong; Lv, Fengting; Tian, Yuanyuan; Cai, Kaiyu; Yang, Bowen; Niu, Jingyi; Zou, Haochen; Liu, Songrui; Xu, Guoliang; Fan, Xing; Hu, Benhui; Loh, Xian Jun; Wang, Lianhui; Chen, Xiaodong (8 August 2022). "A chemically mediated artificial neuron" . Nature Electronics. 5 (9): 586–595. doi:10.1038/s41928-022-00803-0. hdl: 10356/163240 . ISSN   2520-1131. S2CID   251464760.
  81. ↑ "Scientists create tiny devices that work like the human brain". The Independent. April 20, 2020. Archived from the original on April 24, 2020. Retrieved May 17, 2020.
  82. ↑ "Researchers unveil electronics that mimic the human brain in efficient learning". phys.org. Archived from the original on May 28, 2020. Retrieved May 17, 2020.
  83. ↑ Fu, Tianda; Liu, Xiaomeng; Gao, Hongyan; Ward, Joy E.; Liu, Xiaorong; Yin, Bing; Wang, Zhongrui; Zhuo, Ye; Walker, David J. F.; Joshua Yang, J.; Chen, Jianhan; Lovley, Derek R.; Yao, Jun (April 20, 2020). "Bioinspired bio-voltage memristors". Nature Communications. 11 (1): 1861. Bibcode:2020NatCo..11.1861F. doi: 10.1038/s41467-020-15759-y . PMC   7171104 . PMID   32313096.
  84. ↑ Bolakhe, Saugat. "Lego Robot with an Organic 'Brain' Learns to Navigate a Maze". Scientific American. Retrieved 1 February 2022.
  85. ↑ Krauhausen, Imke; Koutsouras, Dimitrios A.; Melianas, Armantas; Keene, Scott T.; Lieberth, Katharina; Ledanseur, Hadrien; Sheelamanthula, Rajendar; Giovannitti, Alexander; Torricelli, Fabrizio; Mcculloch, Iain; Blom, Paul W. M.; Salleo, Alberto; Burgt, Yoeri van de; Gkoupidenis, Paschalis (December 2021). "Organic neuromorphic electronics for sensorimotor integration and learning in robotics". Science Advances. 7 (50): eabl5068. Bibcode:2021SciA....7.5068K. doi:10.1126/sciadv.abl5068. hdl:10754/673986. PMC   8664264 . PMID   34890232. S2CID   245046482.
  86. ↑ Sarkar, Tanmoy; Lieberth, Katharina; Pavlou, Aristea; Frank, Thomas; Mailaender, Volker; McCulloch, Iain; Blom, Paul W. M.; Torriccelli, Fabrizio; Gkoupidenis, Paschalis (7 November 2022). "An organic artificial spiking neuron for in situ neuromorphic sensing and biointerfacing". Nature Electronics. 5 (11): 774–783. doi: 10.1038/s41928-022-00859-y . hdl: 10754/686016 . ISSN   2520-1131. S2CID   253413801.
  87. ↑ "Artificial neurons emulate biological counterparts to enable synergetic operation". Nature Electronics. 5 (11): 721–722. 10 November 2022. doi:10.1038/s41928-022-00862-3. ISSN   2520-1131. S2CID   253469402.
  88. 1 2 3 Grote M (September 2011). "Jeewanu, or the 'particles of life'. The approach of Krishna Bahadur in 20th century origin of life research". Journal of Biosciences. 36 (4): 563–570. doi:10.1007/s12038-011-9087-0. PMID   21857103. S2CID   19551399.
  89. ↑ Caren LD, Ponnamperuma C (1967). A review of some experiments on the synthesis of 'Jeewanu'. NASA Technical Memorandum X-1439. National Aeronautics and Space Administration. CiteSeerX   10.1.1.691.9322 . OCLC   761398715.
  90. ↑ "Engineers Made Themselves Some Cyborg Cells". Popular Mechanics. 2023-01-11. Retrieved 2023-01-13.
  91. ↑ "'Cyborg' bacteria deliver green fuel source from sunlight". BBC News. 2017-08-22. Retrieved 2023-01-13.
  92. ↑ Peplow, Mark (2005-10-17). "Cyborg cells sense humidity". Nature. doi:10.1038/news051017-3. ISSN   1476-4687.
  93. ↑ Berry, Vikas; Saraf, Ravi F. (2005-10-21). "Self-Assembly of Nanoparticles on Live Bacterium: An Avenue to Fabricate Electronic Devices". Angewandte Chemie International Edition. 44 (41): 6668–6673. doi: 10.1002/anie.200501711 . ISSN   1433-7851. PMID   16215974. S2CID   15662656.
  94. ↑ "Cyborg bacteria outperform plants when turning sunlight into useful compounds (video)". American Chemical Society. Retrieved 2023-01-13.
  95. ↑ Sakimoto, Kelsey K.; Wong, Andrew Barnabas; Yang, Peidong (2016-01-01). "Self-photosensitization of nonphotosynthetic bacteria for solar-to-chemical production". Science. 351 (6268): 74–77. Bibcode:2016Sci...351...74S. doi: 10.1126/science.aad3317 . ISSN   0036-8075. PMID   26721997. S2CID   206642914.
  96. ↑ Kornienko, Nikolay; Sakimoto, Kelsey K.; Herlihy, David M.; Nguyen, Son C.; Alivisatos, A. Paul; Harris, Charles. B.; Schwartzberg, Adam; Yang, Peidong (2016-10-18). "Spectroscopic elucidation of energy transfer in hybrid inorganic–biological organisms for solar-to-chemical production". Proceedings of the National Academy of Sciences. 113 (42): 11750–11755. Bibcode:2016PNAS..11311750K. doi: 10.1073/pnas.1610554113 . ISSN   0027-8424. PMC   5081607 . PMID   27698140.
  97. ↑ Contreras-Llano, Luis E.; Liu, Yu-Han; Henson, Tanner; Meyer, Conary C.; Baghdasaryan, Ofelya; Khan, Shahid; Lin, Chi-Long; Wang, Aijun; Hu, Che-Ming J.; Tan, Cheemeng (2023-01-11). "Engineering Cyborg Bacteria Through Intracellular Hydrogelation". Advanced Science. 10 (9): 2204175. doi:10.1002/advs.202204175. ISSN   2198-3844. PMC   10037956 . PMID   36628538. S2CID   255593443.
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