RESEARCH FOCUS OF THE FACILITY:

          1. Adult Stem Cells

                  i)   Bone Marrow derived Mesenchymal Stem Cells (MSC)

Mesenchymal Stem Cells are a rare population of Stem Cells in the Bone Marrow niche apart from the Hematopoietic Stem Cells. The MSCs are a potential candidate for Cell Replacement Approaches in the Degenerative Disorders.

Therefore, we at Stem Cell Facility are undertaking basic research for studying the biology of MSCs. The research primarily involves the study of differentiation potential and various signalling pathways responsible for the same. Specifically we are interested to differentiate these cells into Neurons and Cardiomyocytes.

Also, we are in the process of using these cells in pre-clinical trials for various degenerative disorders. Long term expansion has been standardized for clinical trials.

      ii)   Corneal Epithelial Stem Cells

The ocular surface comprises of the cornea, the conjunctiva and the limbus which is the transitional zone between the two. The main function of the cornea is to provide a smooth and transparent surface. The corneal epithelium is generated by the limbal epithelial stem cells (LESC) .

      When these LESC are dysfunctional or destroyed this condition is known as limbal stem cell deficiency (LSCD). LSCD is one of the major causes of the loss of corneal transparency. LSCD may be due to ocular surface disease and trauma, which include chemical and thermal burn, aniridia, mild Stevens-Johnson syndrome and ocular pemphigoid.

Various approaches have been adopted to treat LSCD however auto- or allo-limbal stem cells transplantation is a most widely applied method.

At AIIMS, we are routinely doing limbal stem cell transplantation and till now we have done fifty two cases.

                  iii)      Oral mucosal epithelial cells

            Bilateral LSCD where both the eyes are affected, requires allogenous limbal tissue as a source of limbal stem cells, and this necessitates long term use of systemic immunosuppressants to avoid graft rejection.  Immunosuppressants have several side effects that affect the quality of the patient’s life and are expensive. There is also the risk of rejection and graft failure despite immunosuppression. Therefore, sources of autologous tissue that can functionally replace the corneal epithelium have been considered as an alternative to allogenic limbal transplants.  Since the corneal epithelium is of the stratified squamous type, autologous epithelial cells such as oral, conjunctival, nasal, esophageal, rectal, and vaginal epithelia, which all have a similar morphology, could be considered as an alternative to allogenic limbal transplants.  Oral mucosal epithelium is easily available and can be harvested without invasive surgery.  At AIIMS, we are culturing and characterizing oral mucosal epithelium on human amniotic membrane with the aim to reconstruct the ocular surface.   Till now we have done ten cases.

               iv)  Epidermal Stem Cells

Skin and Hair Follicle Stem Cells are the unique source of stem cells. Hair follicle turns out to a non-invasive source of stem cells; Stem cells may be isolated from the plucked hair follicle. Skin is again a little invasive source. We are interested to Isolate and characterize these stem cells with an aim to differentiate these cells into Melanocytes and Keratinocytes. The future goal of this project is to transplant these differentiated cells into the patients of Vitiligo initially and into other skin pathologies later on.

       2. Cancer Stem cells

Several immunotherapeutic strategies like Dendritic cells pulsed with tumor lysate and systemic cytokine treatments have been followed to cure glioma completely. By these methods results are optimistic but disease is not cured completely. In the search of root cause of disease researchers found that a subpopulation of cells are responsible for glioma formation and maintenance and are named as glioma stem cells (GSC).

According to the cancer stem cell hypothesis, a subpopulation of cells within a cancer has the capacity to sustain tumor growth. This subpopulation of cells is made up of cancer stem cells, which are defined simply as the population of cells within a tumor that can self-renew, differentiate, and regenerate a phenocopy of the cancer. Cancer stem cells have now been prospectively isolated from human cancers of the blood, breast, and brain, and putative cancer stem cells have been identified from human skin, bone, and prostate tumors and from multiple established mammalian cancer cell lines.

At the Stem cell facility we focus on the isolation, characterization and culturing of glioma stem cells from glioma patients. We also study the role of immune modulatory cytokines and Interferons (IFN) to modulate the immune profile of glioma stem cells in order to abrogate glioma completely.

      3. Tissue Engineering

Tissue engineering is an emerging multidisciplinary field involving biology, medicine, and engineering that is likely to revolutionize the ways we improve the health and quality of life for millions of people worldwide by restoring, maintaining, or enhancing tissue and organ function.

Our mission is to develop technologies that will translate into safe and effective clinical therapies. The research focuses on understanding the molecular basis for bone formation and wound healing, and applying this knowledge to engineer tissues using therapeutic systems of biomaterials, cells and signaling molecules.

Mesenchymal Stem cells derived from the patient Bone Marrow are also being considered as precursors for preparing bone tissue in clinically useful quantities. It is very difficult to engineer bone directly, due to the deterioration of differentiated bone cells (osteocytes) while they are being grown in vitro. Bone regrowth within the patient's body can be achieved under favorable conditions by implanting calcium salts, possibly formed or contained within a titanium or soluble polymer mesh, directly into the patient's body. Cells attach to the scaffolds and reorganize them to form functional tissue by proliferating, synthesizing extracellular matrix, and migrating along the scaffold.

It is hoped that the MSCs, once implanted in appropriate locations in the body, will quickly differentiate to generate the required bone tissue. Studies are currently underway to see how these cells are activated and recruited in the body.

 4.  Induced Pluripotent Stem Cells

Induced pluripotent stem (iPS) cells are human somatic cells that have been reprogrammed to a pluripotent state especially cells with the properties of Embryonic Stem Cells (ESC) which than can be used for patient-specific cell therapy.

Reprogramming of somatic cells include introduction of four genes responsible for maintaining pluripotency and self-renewal of stem cells using viral approach.

There are several hurdles to be overcome before iPS can be considered as a potential patient-specific cell therapy, and it will be crucial to characterize the development potential of human iPS cell lines. 

In our facility we are aiming Induction, derivation and characterization of disease specific human iPS cells and to compare the reprogramming efficiency of cells from initial and later stages of differentiation.