Amniotic stem cells

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Amniotic stem cells are the mixture of stem cells that can be obtained from the amniotic fluid [1] [2] as well as the amniotic membrane. [3] They can develop into various tissue types including skin, cartilage, cardiac tissue, nerves, muscle, and bone. [4] The cells also have potential medical applications, especially in organ regeneration. [5]

Contents

The stem cells are usually extracted from the amniotic sac by amniocentesis which occurs without harming the embryos. The use of amniotic fluid stem cells is therefore generally considered to lack the ethical problems associated with the use of cells from embryos. [1]

History

The presence of embryonic and foetal cells from all germ layers in the amniotic fluid was gradually determined since the 1980s. Haematopoietic progenitor cells were first reported to be present in the amniotic fluid in 1993, specifically up to the 12th week of pregnancy. It was suggested that these originated from the yolk sac. [1]

In 1996, a study indicated that non-haematopoietic progenitor cells were also present in the amniotic fluid. This was later confirmed as mesenchymal stem cells were obtained. In addition, evidence indicated that embryonic stem cells are part of the fluid, although in very small quantities. [1]

At around the same time, it was determined that stem cells from the amniotic membrane also have multipotent potential. AS their differentiation into neural and glial cells as well as hepatocyte precursors was observed. [1]

Properties

The majority of stem cells present in the amniotic fluid share many characteristics, which suggests they may have a common origin. [1]

In 2007, it was confirmed that the amniotic fluid contains a heterogeneous mixture of multipotent cells after it was demonstrated that they were able to differentiate into cells from all three germ layers but they could not form teratomas following implantation into immunodeficient mice. This characteristic differentiates them from embryonic stem cells but indicates similarities with adult stem cells. [6] However, foetal stem cells attained from the amniotic fluid are more stable and more plastic than their adult counterparts making it easier for them to be reprogrammed to a pluripotent state. [7] [8]

A variety of techniques has been developed for the isolation and culturing of amniotic stem cells. One of the more common isolation methods involves the removal of amniotic fluid by amniocentesis. The cells are then extracted from the fluid based on the presence of c-Kit. Several variations of this method exist. There is some debate whether c-Kit is a suitable marker to distinguish amniotic stem cells from other cell types because cells lacking c-Kit also display differentiation potential. Culture conditions may also be adjusted to promote the growth of a particular cell type. [6]

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are highly abundant in the amniotic fluid and several techniques have been described for their isolation. They usually involve the removal of amniotic fluid by amniocentesis and their distinction from other cells may be based on their morphology or other characteristics. [1]

Human leukocyte antigen testing has been utilised to confirm that the MSCs stem from the fetus and not from the mother. Originally it was proposed that the MSCs were discarded from the embryo at the end of their life cycle but since the cells remained viable in the amniotic fluid and were able to proliferate in culture this hypothesis was overturned. However, it remains unclear whether the cells originate from the fetus itself, the placenta or possibly the inner cell mass of the blastocyst. [1]

Comparison of amniotic fluid-derived MSCs to bone-marrow-derived ones showed that the former has a higher expansion potential in culture. However, the cultured amniotic fluid-derived MSCs have a similar phenotype to both adult bone-marrow-derived MSCs and MSCs originating from second trimester fetal tissue. [1] In animals, the MSCs seem to have a unique immunological profile which was observed after their isolation and in vitro culturing. [1]

Embryonic-like stem cells

As opposed to mesenchymal stem cells, embryonic-like stem cells are not abundant in the amniotic fluid, making up less than 1% of amniocentesis samples. Embryonic-like stem cells were originally identified using markers common to embryonic stem cells such as nuclear Oct4, CD34, vimentin, alkaline phosphatase, stem cell factor and c-Kit. However, these markers were not necessarily concomitantly expressed. In addition, all of these markers can occur on their own or in some combination in other types of cells. [1]

The pluripotency of these embryonic-like stem cells remains to be fully established. Although those cells which expressed the markers were able to differentiate into muscle, adipogenic, osteogenic, nephrogenic, neural and endothelial cells, this did not necessarily occur from a homogenous population of undifferentiated cells. Evidence in favour of their embryonic stem cell nature is the cells' ability to produce clones. [1]

Clinical applications

The use of amniotic stem cells instead of embryonic stem cells may be advantageous in some cases for various reasons including that the former do not form teratomas. [6] Their enhanced stability and plasticity compared to adult stem cells may also be an advantage. [7] Stem cells from both the amniotic fluid and membrane are utilised for therapeutic approaches. [9] [3]

Foetal tissue engineering

Possible applications include the use of amniotic stem cells for foetal tissue engineering to reconstruct birth defects in infants. This would circumvent the complications that are often associated with harvesting stem cells from foetal tissue. A small amount of amniotic fluid provides a large enough quantity of cells for the tissue engineering process and could help correct a number of defects including diaphragmatic hernia and possibly repair premature membrane rupture during pregnancy. If frozen and banked, the cells may also be used for similar purpose later in life. [1]

Cardiovascular tissue engineering

Several studies have been carried out to investigate the potential of amniotic stem cells to differentiate into cardiac cells. Although c-Kit sorted cells express some genes common in cardiac cells, success in this area is still limited. [6] Co-culturing, i.e. mixing cells and plating them together, of human amniotic stem cells with neonatal rat ventricular myocytes (NRVM) caused the cells to form functional gap junctions with each other, an indicator for cardiac-like cells. [10] However, these results may be due to the specific features of the NRVM or fusion of the cells rather than the amniotic stem cell's own potential to differentiate into cardiac cells. In general, these types of techniques are considered to be potentially significant but further investigations are required. [6]

Another area of interest is the use of these cells for improvement of cardiac tissue following a myocardial infarction. Several strategies have been tested in rats including the injection of dissociated amniotic stem cells into the infarct region, which yielded conflicting results from several research groups. [6] In contrast, injection of amniotic stem cell aggregates seems to improve the function of the tissue significantly by reducing the size of the infarct area and improving the function of the left ventricle. [11] [12] In addition, vasculature density has been shown to increase. [12] Injection of cells immediately following the infarct is particularly beneficial as the cells protect the cardiac tissue from further damage. [13]

Moreover, other findings have brought the proof of concept that secretome of amniotic stem cell could act as an effective paracrine agent against Doxorubicin induced cardiotoxicity, [14] confirming the potential importance of this cellular population in the field of cardiological research.

Kidney injury repair

Following the discovery that amniotic stem cells are able to differentiate into renal cells, this was further explored in several studies. [7] These showed that in vitro the cells were able to contribute to early kidney structures as well as being able to integrate into early kidney structures ex vivo and continue their development into mature nephrons. [15] Results obtained for the use of amniotic stem cells in the postnatal kidney were far less encouraging as the cell's contribution to the tissue was very small. However, the cells were able to exert a protective effect on tubular cells in mice with acute tubular necrosis. [16]

Amniotic stem cells can also be used to treat chronic damage. This was shown in mouse models for Alport syndrome, where the cells prolonged survival of the animals by slowing down the progression of the disease. [17] The same effect was observed in mouse models where human amniotic stem cells were used to treat uretral obstruction. [18]

Ethical Considerations

The use of fetal cells has been highly controversial because the tissue is usually obtained from the fetus following induced abortion. In contrast, fetal stem cells in the amniotic fluid can be obtained through routine prenatal testing without the need for abortion or fetal biopsy.

See also

Related Research Articles

<span class="mw-page-title-main">Stem cell</span> Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

<span class="mw-page-title-main">Amniocentesis</span> Sampling of amniotic fluid done mainly to detect fetal chromosomal abnormalities

Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is necessary to conclusively diagnose the majority of genetic disorders, with amniocentesis being the gold-standard procedure after 15 weeks' gestation.

<span class="mw-page-title-main">Chorionic villus sampling</span> Type of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus

Chorionic villus sampling (CVS), sometimes called "chorionic villous sampling", is a form of prenatal diagnosis done to determine chromosomal or genetic disorders in the fetus. It entails sampling of the chorionic villus and testing it for chromosomal abnormalities, usually with FISH or PCR. CVS usually takes place at 10–12 weeks' gestation, earlier than amniocentesis or percutaneous umbilical cord blood sampling. It is the preferred technique before 15 weeks.

<span class="mw-page-title-main">Amniotic fluid</span> Fluid surrounding a fetus within the amnion

The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products between mother and fetus.

<span class="mw-page-title-main">Embryonic stem cell</span> Type of pluripotent blastocystic stem cell

Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (embryoblast) using immunosurgery results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage have the same moral considerations as embryos in the post-implantation stage of development.

<span class="mw-page-title-main">Cell therapy</span> Therapy in which cellular material is injected into a patient

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.

Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, "bed covering", and Ancient Greek στρῶμα, strôma, "bed".

<span class="mw-page-title-main">Adult stem cell</span> Multipotent stem cell in the adult body

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells, they can be found in juvenile, adult animals, and humans, unlike embryonic stem cells.

Stem-cell therapy uses stem cells to treat or prevent a disease or condition. As of 2016, the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone marrow transplantation, but the cells can also be derived from umbilical cord blood. Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease.

Mesenchymal stem cells (MSCs) are multipotent cells found in multiple human adult tissues, including bone marrow, synovial tissues, and adipose tissues. Since they are derived from the mesoderm, they have been shown to differentiate into bone, cartilage, muscle, and adipose tissue. MSCs from embryonic sources have shown promise scientifically while creating significant controversy. As a result, many researchers have focused on adult stem cells, or stem cells isolated from adult humans that can be transplanted into damaged tissue.

<span class="mw-page-title-main">Fetal membranes</span> Amnion and chorion which surround and protect a developing fetus

The fetal membranes are the four extraembryonic membranes, associated with the developing embryo, and fetus in humans and other mammals. They are the amnion, chorion, allantois, and yolk sac. The amnion and the chorion are the chorioamniotic membranes that make up the amniotic sac which surrounds and protects the embryo. The fetal membranes are four of six accessory organs developed by the conceptus that are not part of the embryo itself, the other two are the placenta, and the umbilical cord.

<span class="mw-page-title-main">Osteochondroprogenitor cell</span>

Osteochondroprogenitor cells are progenitor cells that arise from mesenchymal stem cells (MSC) in the bone marrow. They have the ability to differentiate into osteoblasts or chondrocytes depending on the signalling molecules they are exposed to, giving rise to either bone or cartilage respectively. Osteochondroprogenitor cells are important for bone formation and maintenance.

<span class="mw-page-title-main">Cell potency</span> Ability of a cell to differentiate into other cell types

Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.

<span class="mw-page-title-main">Mesenchymal stem cell</span> Multipotent, non-hematopoietic adult stem cells present in multiple tissues

Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts, chondrocytes, myocytes and adipocytes.

Adult mesenchymal stem cells are being used by researchers in the fields of regenerative medicine and tissue engineering to artificially reconstruct human tissue which has been previously damaged. Mesenchymal stem cells are able to differentiate, or mature from a less specialized cell to a more specialized cell type, to replace damaged tissues in various organs.

Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

A Muse cell is an endogenous non-cancerous pluripotent stem cell. They reside in the connective tissue of nearly every organ including the umbilical cord, bone marrow and peripheral blood. They are collectable from commercially obtainable mesenchymal cells such as human fibroblasts, bone marrow-mesenchymal stem cells and adipose-derived stem cells as 1~several percent of the total population. Muse cells are able to generate cells representative of all three germ layers from a single cell both spontaneously and under cytokine induction. Expression of pluripotency genes and triploblastic differentiation are self-renewable over generations. Muse cells do not undergo teratoma formation when transplanted into a host environment in vivo. This can be explained in part by their intrinsically low telomerase activity, eradicating the risk of tumorigenesis through unbridled cell proliferation. They were discovered in 2010 by Mari Dezawa and her research group. Clinical trials for acute myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, amyotrophic lateral sclerosis, acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection, are conducted. Physician-led clinical trial for neonatal hypoxic-ischemic encephalopathy was also started. The summary results of a randomized double-blind placebo-controlled clinical trial in patients with stroke was announced.

Cord lining, cord tissue, or umbilical cord lining membrane, is the outermost layer of the umbilical cord. As the umbilical cord itself is an extension of the placenta, the umbilical cord lining membrane is an extension of the amniotic membrane covering the placenta. The umbilical cord lining membrane comprises two layers: the amniotic layer and the sub-amniotic layer. The umbilical cord lining membrane is a rich source of two strains of stem cells (CLSCs): epithelial stem cells (CLECs) and mesenchymal stem cells (CLMCs). Discovered by Singapore-based CellResearch Corporation in 2004, this is the best known source for harvesting human stem cells.

Rh factor testing, also known as Rhesus factor testing, is the procedure of determining the Rhesus D status of an individual.

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References

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