Tissue Engineering and Regenerative Medicine

Mesenchymal stem cells (MSCs), due to their paracrine, anti-inflammatory and wound healing applications, have emerged as a promising treatment option for various human diseases. However, the efficacy of MSC therapy is currently limited by low retention and poor survival of transplanted cells as demonstrated consistently by clinical studies using bone marrow-MSCs. This is due to the harsh microenvironment marked by oxygen and nutrient deprivation and inflammation at the injured sites. Also, the choice of MSC source could be critical in determining fate and cellular function of MSCs. Therefore, our objective was to investigate the influence of ischemic stress on Wharton’s Jelly (WJ)-MSCs from the umbilical cord, to assess their therapeutic relevance in ischemic diseases. We simulated conditions of ischemia in-vitro by culturing WJ-MSCs under 2% oxygen in a serum deprived and low glucose medium for 48 hrs. Under ischemic stress, WJ-MSCs retained a viable population of greater than 80%. Ischemic WJ-MSCs got arrested at G0/G1 phase of cell cycle but did not show signs of senescence. Moreover, the ischemic WJ-MSCs expressed the characteristic MSC surface antigens and in addition, were negative for the expression of costimulatory molecules, thus maintaining their immuneprivilged status under ischemia. To evaluate the wound healing properties of ischemic WJ-MSCs, we compared gene expression profile between control and ischemic WJ-MSCs by PCR array and found an upregulation of many ECM and adhesion molecules, cytokines, trophic factors in the ischemic population. Our findings thus provide evidence that WJ-MSCs might be therapeutically beneficial and potent in treating ischemic diseases.