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Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biological tissues. Tissue engineering often involves the use of cells placed on tissue scaffolds in the formation of new viable tissue for a medical purpose, but is not limited to applications involving cells and tissue scaffolds. While it was once categorized as a sub-field of biomaterials, having grown in scope and importance, it can is considered as a field of its own.
Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.
Cardiomyoplasty is a surgical procedure in which healthy muscle from another part of the body is wrapped around the heart to provide support for the failing heart. Most often the latissimus dorsi muscle is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged myocardium to be treated in other ways, such as remodeling by cellular therapies.
Doris Anita Taylor, Ph.D., FACC, FAHA is an American scientist working in regenerative medicine and tissue engineering. She was the Director, Regenerative Medicine Research and Director, Center for Cell and Organ Biotechnology at the Texas Heart Institute in Houston, Texas until March 2020. She is the Co-Founder of Miromatrix Medical, Inc. and Co-Founder of Organamet Bio, Inc.
A fibrin scaffold is a network of protein that holds together and supports a variety of living tissues. It is produced naturally by the body after injury, but also can be engineered as a tissue substitute to speed healing. The scaffold consists of naturally occurring biomaterials composed of a cross-linked fibrin network and has a broad use in biomedical applications.
Acellular dermis is a type of biomaterial derived from processing human or animal tissues to remove cells and retain portions of the extracellular matrix (ECM). These materials are typically cell-free, distinguishing them from classical allografts and xenografts, can be integrated or incorporated into the body, and have been FDA approved for human use for more than 10 years in a wide range of clinical indications.
In tissue engineering, neo-organ is the final structure of a procedure based on transplantation consisting of endogenous stem/progenitor cells grown ex vivo within predesigned matrix scaffolds. Current organ donation faces the problems of patients waiting to match for an organ and the possible risk of the patient's body rejecting the organ. Neo-organs are being researched as a solution to those problems with organ donation. Suitable methods for creating neo-organs are still under development. One experimental method is using adult stem cells, which use the patients own stem cells for organ donation. Currently this method can be combined with decellularization, which uses a donor organ for structural support but removes the donors cells from the organ. Similarly, the concept of 3-D bioprinting organs has shown experimental success in printing bioink layers that mimic the layer of organ tissues. However, these bioinks do not provide structural support like a donor organ. Current methods of clinically successful neo-organs use a combination of decellularized donor organs, along with adult stem cells of the organ recipient to account for both the structural support of a donor organ and the personalization of the organ for each individual patient to reduce the chance of rejection.
Cellular cardiomyoplasty, or cell-based cardiac repair, is a new potential therapeutic modality in which progenitor cells are used to repair regions of damaged or necrotic myocardium. The ability of transplanted progenitor cells to improve function within the failing heart has been shown in experimental animal models and in some human clinical trials. In November 2011, a large group of collaborators at Minneapolis Heart Institute Foundation at Abbott Northwestern found no significant difference in left ventricular ejection fraction (LVEF) or other markers, between a group of patients treated with cellular cardiomyoplasty and a group of control patients. In this study, all patients were post MI, post percutaneous coronary intervention (PCI) and that infusion of progenitor cells occurred 2–3 weeks after intervention. In a study that is currently underway, however, more positive results were being reported: In the SCIPIO trial, patients treated with autologous cardiac stem cells post MI have been reported to be showing statistically significant increases in LVEF and reduction in infarct size over the control group at four months after implant. Positive results at the one-year mark are even more pronounced. Yet the SCIPIO trial "was recently called into question". Harvard University is "now investigating the integrity of some of the data". The Lancet recently published a non-specific ‘Expression of concern’ about the paper. Subsequently, another preclinical study also raised doubts on the rationale behind using this special kind of cell, as it was found that the special cells only have a minimal ability in generating new cardiomyocytes. Some specialists therefore now raise concerns to continue.
An organ-on-a-chip (OOC) is a multi-channel 3-D microfluidic cell culture, integrated circuit (chip) that simulates the activities, mechanics and physiological response of an entire organ or an organ system. It constitutes the subject matter of significant biomedical engineering research, more precisely in bio-MEMS. The convergence of labs-on-chips (LOCs) and cell biology has permitted the study of human physiology in an organ-specific context. By acting as a more sophisticated in vitro approximation of complex tissues than standard cell culture, they provide the potential as an alternative to animal models for drug development and toxin testing.
Decellularization is the process used in biomedical engineering to isolate the extracellular matrix (ECM) of a tissue from its inhabiting cells, leaving an ECM scaffold of the original tissue, which can be used in artificial organ and tissue regeneration. Organ and tissue transplantation treat a variety of medical problems, ranging from end organ failure to cosmetic surgery. One of the greatest limitations to organ transplantation derives from organ rejection caused by antibodies of the transplant recipient reacting to donor antigens on cell surfaces within the donor organ. Because of unfavorable immune responses, transplant patients suffer a lifetime taking immunosuppressing medication. Stephen F. Badylak pioneered the process of decellularization at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. This process creates a natural biomaterial to act as a scaffold for cell growth, differentiation and tissue development. By recellularizing an ECM scaffold with a patient’s own cells, the adverse immune response is eliminated. Nowadays, commercially available ECM scaffolds are available for a wide variety of tissue engineering. Using peracetic acid to decellularize ECM scaffolds have been found to be false and only disinfects the tissue.
Endogenous cardiac stem cells (eCSCs) are tissue-specific stem progenitor cells harboured within the adult mammalian heart. It has to be noted that a scientific-misconduct scandal, involving Harvard professor Piero Anversa, might indicate that the heart stem cell concept be broken. Therefore, the following article should be read with caution, as it builds on Anversa's results.
Decellularization of porcine heart valves is the removal of cells along with antigenic cellular elements by either physical or chemical decellularization of the tissue. This decellularized valve tissue provides a scaffold with the remaining extracellular matrix (ECM) that can then be used for tissue engineering and valve replacement in humans inflicted with valvular disease. Decellularized biological valves have potential benefit over conventional valves through decreased calcification which is thought to be an immuno-inflammatory response initiated by the recipient.
Human engineered cardiac tissues (hECTs) are derived by experimental manipulation of pluripotent stem cells, such as human embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs) to differentiate into human cardiomyocytes. Interest in these bioengineered cardiac tissues has risen due to their potential use in cardiovascular research and clinical therapies. These tissues provide a unique in vitro model to study cardiac physiology with a species-specific advantage over cultured animal cells in experimental studies. hECTs also have therapeutic potential for in vivo regeneration of heart muscle. hECTs provide a valuable resource to reproduce the normal development of human heart tissue, understand the development of human cardiovascular disease (CVD), and may lead to engineered tissue-based therapies for CVD patients.
Fujifilm Cellular Dynamics, Inc. (FCDI) is a large scale manufacturer of human cells, created from induced pluripotent stem cells, for use in basic research, drug discovery and regenerative medicine applications.
Regeneration in humans is the regrowth of lost tissues or organs in response to injury. This is in contrast to wound healing, or partial regeneration, which involves closing up the injury site with some gradation of scar tissue. Some tissues such as skin, the vas deferens, and large organs including the liver can regrow quite readily, while others have been thought to have little or no capacity for regeneration following an injury.
Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.
Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement. Currently, there are over a quarter of a million prosthetic heart valves implanted annually, and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. Thus, in situ (in its original position or place) tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system.
Milica Radisic is a Serbian Canadian tissue engineer, academic and researcher. She is a professor at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering, and the Department of Chemical Engineering and Applied Chemistry. She co-founded TARA Biosystems and is a senior scientist at the Toronto General Hospital Research Institute.
Katja Schenke-Layland is the Professor of Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine at the University of Tübingen. She is the Director of the NMI Natural and Medical Sciences Institute at the University Tübingen in Reutlingen, Study Dean of Medical Technologies at the University of Tübingen, and Founding Director of the Institute of Biomedical Engineering at the Medical Faculty of the University Tübingen. She is also the Founding Director of the 3R Center for In Vitro Models and Alternatives to Animal Testing Tübingen.
Cardiomyocyte proliferation refers to the ability of cardiac muscle cells to progress through the cell cycle and continue to divide. Traditionally, cardiomyocytes were believed to have little to no ability to proliferate and regenerate after birth. Although other types of cells, such as gastrointestinal epithelial cells, can proliferate and differentiate throughout life, cardiac tissue contains little intrinsic ability to proliferate, as adult human cells arrest in the cell cycle. However, a recent paradigm shift has occurred. Recent research has demonstrated that human cardiomyocytes do proliferate to a small extent for the first two decades of life. Also, cardiomyocyte proliferation and regeneration has been demonstrated to occur in various neonatal mammals in response to injury in the first week of life. Current research aims to further understand the biological mechanism underlying cardiomyocyte proliferation in hopes to turn this capability back on in adults in order to combat heart disease.
References
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- ↑ Highfield, Roger (January 13, 2008). "First bioartificial heart may signal end of organ shortage". The Telegraph. Retrieved February 10, 2016.
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- ↑ Mozaffarian, Dariush; et al. (2015). "Heart Disease and Stroke Statistics—2015 Update". Circulation. 131 (4): e29-322. doi: 10.1161/cir.0000000000000152 . PMID 25520374. S2CID 30224225.
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{{cite journal}}: CS1 maint: multiple names: authors list (link) - ↑ Vagnozzi, Ronald J.; Maillet, Marjorie; Sargent, Michelle A.; Khalil, Hadi; Johansen, Anne Katrine Z.; Schwanekamp, Jennifer A.; York, Allen J.; Huang, Vincent; Nahrendorf, Matthias; Sadayappan, Sakthivel; Molkentin, Jeffery D. (16 January 2020). "An acute immune response underlies the benefit of cardiac stem cell therapy". Nature. 577 (7790): 405–409. doi:10.1038/s41586-019-1802-2. PMC 6962570 . PMID 31775156.
- ↑ Traphagen, S; Yelick, PC (September 2009). "Reclaiming a natural beauty: whole-organ engineering with natural extracellular materials". Regenerative Medicine. 4 (5): 747–58. doi:10.2217/rme.09.38. PMC 3021746 . PMID 19761399.
- 1 2 Laflamme, Michael A; Murry, Charles E (July 2005). "Regenerating the heart". Nature Biotechnology. 23 (7): 845–856. doi:10.1038/nbt1117. PMID 16003373. S2CID 8265954.