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Regenerative Medicine

Regenerative Medicine:

Regenerative medicine is a niche area in medicine where diseases caused by cell death and consequent loss of function can be replaced by healthy cells, thereby restoring the function. Autologous tissue grafting procedures can be effectively replaced by allogeneic mesenchymal stem cells, which are an attractive alternative source of cells to repair defects. An allogeneic bank catering to the requirements of the sector can be developed where cells from the donor can be isolated and expanded, providing a ready source of committed progenitors for stem cell therapy. A sudden explosion of stem cell banks and research is proof that allogeneic banks in the stem cell niche is here to stay. Stem cell therapy is widely used in the treatment of leukemia, cardiovascular diseases, lung diseases, spinal cord injuries, bone and cartilage repair. In stem cell therapy, autologous and allogenic stem cells are introduced into the patient. MSC cells express low levels of MHC Class I but do not express MHC class II, and antigens such as CD80 and CD 86 and hence these MSC’s are suitable for allogenic as well as xenogenic transplantation. Low level of expression of MHC Class I helps transplanted cells from attack of natural killer cell mediated lysis. MSC also help in the recovery of injuries. MSC are having capacity for homing beacon for tissue repair, inflammation capacity to down regulate immune response. Due to this property of MSC, it is acceptable for cellular treatment for cardiovascular diseases. MSCs have the ability of regeneration of heart muscles through in vitro technique. MSC’s are maintained in host tissues for longer time which is a gold standard property for cellular therapeutics in heart tissue transplantation.

The use of MSC’s is emerging as a new era of cellular therapeutics for the treatment of cancer. In recent research studies, it has been found that engineered MSC’s synthesize and transport apoptosis inducing ligand-related tumour necrotic factor which kills lung metastatic cancer cells. In another study, a combination of 5-flurouracil and IFN-b transduced into MSCs showed a reduction in lung tumor burden in SCID mouse.

MSC based cell therapy is the best replacement for orthotropic liver transplantation. MSC are having capacity to differentiate into endodermal lineages, MSC shows hepatic markers characterizing the developmental stages in liver development. Lately, there have been a number of experimental evidences which proves the role of undifferentiated MSC in recovery of recipient liver and enhanced differentiation of endogenous parenchymal cells and degradation of fibrous matrix. Anti-inflammatory and anti-fibrosis is the unique characteristics of MSC which makes it applicable for liver cirrhosis therapeutics.

MSC increases the regulation of hyaluronic acid, GAGs and expression of important genes like SOX9, COMP, Collagen type II and FMOD which makes it suitable for cartilage repair and regeneration. In recent research, MSC’s were introduced to a new technique called osteochondral integration which involved sandwiching a layer of chondrogenic and osteogenic cells. The result of this study suggested that the sandwiching technique using MSC’s gives a better scaffold and tissue integration. It has been shown that the stem cells are ideal to be transplanted into the retina for the treatment of degenerative diseases like age-related macular degeneration, Stargardt’s disease and retinitis pigmentosa. The retina is a light-sensitive layer of the tissue lining the inner surface of the eye. In the vertebrates, the retinal stem cells exists at the margin of the retina near the junction with the ciliary epithelium from where these stem cells can be isolated and grown in vitro. It has also been proved that the retinal progenitor cells change their competency over time under the influence of intrinsic factors like the transcriptional factors and extrinsic factors like the growth factors. Parkinson disease is a neurodegenerative disease. In this disease, there is decrease in striatal dopamine and also loss of midbrain dopamine neurons. For Parkinson’s diseases, cell based treatment is a promising therapy which is widely utilized in patients. MSC’s protect the damaged tissue and have the capacity to differentiate into dopamine neurons which help in the recovery of lost cells. In a research study where MSC’s were genetically modified and tested in-vivo, it was shown that these MSC’s were successfully capable of migration, survival and differentiation into periventricular astrocytes and olfactory bulb neuron. In the advanced stem cell therapeutics, MSC’s have found its way to treat diabetes wherein the non-functional ß cells of the pancreas are replaced by MSC-derived beta cells by Islet transplantation. Genes responsible for pancreatic endocrine development are expressed by umbilical cord derived MSC. In a recent study it was found that, cord blood stem cells expressed higher levels of pluripotent stem cells and pancreatic endodermal stem cell markers; this study is useful for future therapeutics in the developmental protocols for differentiation of MSC into beta cells.

Autologous MSC (auto-MSC) applications have some potential limitations. First, it is difficult to obtain sufficient auto-MSCs from some patients—for example, ASCs from thinner patients or BM-MSCs from myelofibrosis patients. Second, MSCs isolated from elderly donors have decreased biological activity, including differentiation and regenerative potential, resulting in disappointing treatment outcomes. Third, some systemic diseases, such as diabetes, rheumatoid arthritis and systemic lupus erythematosus (SLE), alter the intrinsic properties of MSCs, thus impairing their protective function. It is difficult to obtain sufficient quantities of healthy auto-MSCs with high activity from patients with these diseases. MSC implantation in these patients is therefore challenging. Obtaining allogeneic MSCs (allo-MSCs) from young healthy donors is a reasonable approach to resolving this issue. Furthermore, auto-MSC extraction is time-consuming, making it difficult to use them promptly to treat acute diseases such as stroke and myocardial infarction. In contrast, allo-MSCs are readily available and can be administered immediately. In addition, commercial allo-MSC production should guarantee quality control and reduce the cost of cell therapies. Therefore, allo-MSCs are promising alternatives to auto-MSCs, with advantages with regard to time, cost and quality assurance. Above all, the immunosuppressive properties and low immunogenicity of allo- MSCs contribute to a reduced immune response after implantation. The following mechanisms are responsible for their immunosuppression and low immunogenicity. First, their expression of a low or modest level of MHC class I molecules and lack of expression of MHC class II and co-stimulatory molecules, such as CD40, CD80 (B7-1) and CD86 (B7-2), leads to low immunogenicity, thus avoiding immune responses in recipients. Second, MSCs inhibit the activity of various immune cells, including T cells, B cells, natural killer cells, and dendritic cells via cell–cell contacts and soluble factors.

The concept that allo-MSCs may have equivalent efficacy to auto-MSCs has become well established. Currently, different research groups have obtained inconsistent or even contradictory results on the therapeutic effects of allo-MSCs in various studies. Due to the invasive methods employed for bone marrow harvesting, noncontroversial sources of stem cells are being explored. Ageing of Bone marrow derived MSCs should be seriously considered as there is evidence to indicate decreased efficiency of these cells in ageing and proves to be disadvantageous when compared to the fetal origin stem cells present in the umbilical cord.

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