User:Laynap/Amniotic stem cells

Amniotic stem cells are a mixture of stem cells that can be extracted from the amniotic fluid or the amniotic membrane. They can develop into various tissue types including skin, cartilage, cardiac tissue, nerves, muscle, and bone. Additionally, these cells can be utilized in organ regeneration.

Amniocentesis is the process by which amniotic stem cells are extracted. This is a harmless procedure that differs greatly from the use of embryonic stem cells. Embryonic stem cell extraction has many ethical problems to consider; however, the use of amniotic fluid stem cells eliminates these issues.

In 2009, the first US amniotic stem cell bank was opened in Medford, MA, by Biocell Center, an international company specializing in the cryopreservation and private banking of amniotic fluid stem cells.

History

Since the 1980's, there has been a gradual exploration in the presence of embryonic and fetal cells from all germ layers in the amniotic fluid. In 1993, hematopoietic progenitor cells were first cells to reported to be present in the amniotic fluid (specifically up to the 12th week of pregnancy). It was suggested that these cells originated from the yolk sac.

In 1996, a study indicated that were other types of cells in addition to hematopoietic progenitor cells present in the amniotic fluid. These were later confirmed as mesenchymal stem cells. In addition, evidence indicated that embryonic stem cells are part of the fluid, but in very small quantities.

At around the same time, it was determined that stem cells from the amniotic membrane also have multipotent potential. It was found that had neural, glial, and hepatocyte precursors.

Properties

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

In 2007, it was confirmed that the amniotic fluid contains a heterogeneous mixture of multipotent cells. A study showed that these cells could not form teratomas following implantation into immunodeficient mice. However, they were able to differentiate into cells from all three germ layers. This characteristic differentiates them from embryonic stem cells

However, this indicates similarities with adult stem cells. Fetal stem cells attained from the amniotic fluid are more stable and plastic than their adult counterparts, making it easier for them to be reprogrammed to a pluripotent state.

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. 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.

Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are highly abundant in the amniotic fluid and several techniques can be utilized to isolate them. One method involves the removal of amniotic fluid by amniocentesis. They can be distinguished from other cells based on their morphology or other characteristics.

Human leukocyte antigen testing has been utilized to confirm that the MSCs stem from the fetus and not from the mother. It was originally thought that MSCs were discarded from embryo at the end of their life cycle. However, the cells remained viable in the amniotic fluid and developed in a culture, leading to this hypothesis being overturned. It still remains unclear whether the cells originate from the fetus itself, the placenta, or the inner cell mass of the blastocyst.

Comparing 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. In vitro cultures showed that in animals, the MSCs seem to have a unique immunological profile.

Embryonic-like stem cells
As opposed to mesenchymal stem cells, embryonic-like stem cells are not abundant in the amniotic fluid and make 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, making it difficult identify embryonic-like stem cells.

The pluripotency of these embryonic-like stem cells remains to be fully established. Although those cells 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.

Clinical applications
The use of amniotic stem cells instead of embryonic stem cells is advantageous because they do not form teratomas. Also, they have enhanced stability and plasticity compared to adult stem cells. Stem cells from both the amniotic fluid and membrane can also be utilized for therapeutic approaches.

Fetal tissue engineering
Amniotic stem cells can be used for fetal tissue engineering to reconstruct birth defects in infants. This would circumvent the complications that are often associated with harvesting stem cells from fetal tissue. Just a small amount of amniotic fluid provides a large enough quantity of cells for the tissue engineering process. This could help correct a number of defects including diaphragmatic hernia and repairing of premature membrane rupture during pregnancy. If frozen and banked, these cells may also be used for similar purpose later in life.

Cardiovascular tissue engineering
Several studies have been conducted to investigate the potential of amniotic stem cells differentiating into cardiac cells. Although c-Kit sorted cells express some genes common in cardiac cells, success in this area is still limited. Co-culturing (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. This is an indicator for cardiac-like cells. 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. Further investigations are required to confirm what caused the function gap junctions.

A second use of these cells is 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. This yielded conflicting results from several research groups. When injecting the amniotic stem cell, it aggregates and seems to improve the function of the tissue significantly. This is by reducing the size of the infarct area and improving the function of the left ventricle. Additionally, vasculature density has been shown to increase. Injection of cells immediately following the infarct is particularly beneficial as the cells protect the cardiac tissue from further damage.

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. This confirms 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. One study showed how in vitro the cells were able to contribute to early kidney structures. Additionally, they were able to integrate into early kidney structures ex vivo and continue their development into mature nephrons. However, results obtained for the use of amniotic stem cells in the postnatal kidney were far less encouraging since the cell's contribution to the tissue was very small. In mice, he cells were able to exert a protective effect on tubular cells with acute tubular necrosis.

Amniotic stem cells can also be used to treat chronic damage. Mouse models with Alport syndrome were used. The cells prolonged survival of the animals by slowing down the progression of the disease. The same effect was observed in mouse models where human amniotic stem cells were used to treat ureter obstructions.

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.