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Clical Application of Stem Cell

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    Stem cells are undifferentiated cells that can self-renew, multipotent, clonal and can differentiate into any other cell type. Stem cells can, therefore, have the potential to be used as therapy for curing disorders of various kinds such as autoimmune disorders, hemopoietic disorder, metabolism related disorders, cardiovascular disease, etc. Stem cell resides in various organ rather than only in the embryonic stage as it was believed initially. Based on the origin they are classified into embryonic, foetal and adult stem cells. All of them can be used for clinical application.

    Embryonic stem cells are stem cells derived from the inner cell mass of the preimplantation blastocyst and obtained from mice, human and non-human primates. The embryonic stem cells are pluripotent and can replicate indefinitely that is they can able to differentiate into 3 germ layers-ectoderm mesoderm and ectoderm. Their self-renewal capacity and differentiation potential satisfy the requirement application in regenerative medicine, immune disorders, juvenile diabetes, Parkinson’s disease, etc. Arrhythmic heart, when transplanted with hESC-CM cm, showed decreased tachycardia and increased mechanical function.(1)Retinal pigment epithelium for treatment of age related macular degeneration of retina has shown capable of rescuing photoreceptor and improved visual performance in the animal model compared to untreated controls.(2)embryonic stem cell derived neurons for the degeneration of Purkinje neurons.

    Human ESCs can be transplanted into the mice model to study cancer initiation, progression, and method to treat cancer. The tissue in tumor is organized and complex. Kaufman et al have shown that the human ESC when co-cultured with mouse bone marrow stromal cells can generate a hematopoietic precursor and its lineage. Hurdles in ESC based research for therapeutic use is to minimize the teratoma formation and transplant rejection. These problems can be resolved by the use of genetical manipulation of cells, use of feeder-free system, etc.

    iPSC is a pluripotent stem cell. Breakthrough in stem cell biology came with iPSC where pluripotency can be generated from a somatic cell. iPSC has shown resemblance to ESC in morphology, telomerase activity, plurupotencyetc. iPSC has added the advantage of fewer ethical issues when compared to embryonic stem cells. iPSC helps to create defined neuron populations in the case of neurodegenerative and neurovascular disease. iPSC occurs a good candidate for using a system for Parkinson’s disease as they can specifically be made to differentiate A9 DA neurons. For disease modelling and drug testing, 2-dimensional and 3-dimensional culture systems have been developed for Alzheimer’s disease which helps to obtain patient-specific outcomes. The first cardiovascular disease model where iPSC was used was LQTS (hereditary long QT Syndrome) in which iPSC differentiated into ventricular like and atrial like cells showed longer action potential duration. The stem cells are modified in such a way that the drug will target only the metastatic cancer cells rather than harming nearby cells.it targets the niche of the tumour which it resides. The morphology, electrophysiology features, and gene expression profile of human iPSC derived neuron similar to normal neuron, so can be used for treating Huntington disease. Mouse iPSC promote wound healing by regenerating epidermis layer, hair follicles in treating inherited skin disorders.

    Through various paracrine mechanisms, MSC can modulate the progressions of cancer stem cells. The property of migration, ability for immune suppression, regulating proinflammation and antiinflammation make them a candidate for therapy with less adverse effects.

    MSC have the ability to specific tissue activity. MSC has a killing effect on lung cancer, glioma, hepatocarcinomatous, melanoma, etc and has a property to protect itself from immune cells. by the release of PDGF, it can have a growth inhibitory effect on glioma cells. Regulate angiogenesis and cause tumour cell killing by umbilical cord blood-derived MSC. Through regulating mTOR, HIF-α, VEGF signalling axis, MSC derived exosomes can deregulate breast cancer. Some MSC is loaded with the drug to improve its tumour specific effects. MSC with Cx3CL helps to recruit immune cells like NK cells, T cells for targeted cell killing. Subcutaneous melanoma having mice when injected with MSC showed increased apoptosis.

    For a wide variety of malignant and non-malignant diseases, hematopoietic stem cell is the commonly accepted therapy for treatment where the entire immune system is recovered by the transplanted donor’s cells.

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