Anti-apoptotic, Anti-inflammatory and Immunosuppressive Effects of Mesenchymal Stem Cells: Novel Concept for Future Therapies
Authors: Karaoz Erdal 
Published: March 2012

Therapeutic effects of mesenchymal stem cells (MSCs) are believed to occur not only by direct differentiation into injured tissue cells, but also by production of paracrine and autocrine factors. MSCs at the injured tissue environments can promote the secretion of a variety of cytokines and growth factors that have both paracrine and autocrine activities. On this line several studies were performed. For instance, in probing the mechanism of treating effects of MSCs transplanted into the infarcted heart, several researchers noticed that MSCs undergoing hypoxia environments stimulated the infracted heart local microenvironment to secrete more amounts of cardioprotective vital growth factors to inhibit cardiomyocytes’ apoptosis compared with MSCs in vitro cultured under normoxia. Solari et al (2009) examined the immunoregulatory effect of autologous MSCs on sub-optimal numbers of islets co-transplanted into omental pouch to enhance insulin secretion and sustained normoglycemia in a model STZ-induced diabetic rat. They have shown that the allogeneic islets with autologous MSC induced insulin secretion and promoted long-term islet allograft survival.

It has been also demonstrated that in vitro expanded and purified rat MSCs spontaneously secrete transforming growth factor-beta1 (TGF-β1), hepatocyte growth factor (HGF) and IL6, but not interferon gamma (IFNG), IL4, IL5 or IL10. It was considered rather that MSCs promote tissue repair by secreting soluble factors that modulate inflammation and angiogenesis. Oh et al (2009) showed that human MSCs secreted small amount of IL6 while secreting large amount TGF-β1 into the culture medium.

Moreover, increased IL6 secretion was demonstrated when hMSCs were cocultured with chemically-damaged human corneal epithelial cells (hCECs). This is in agreement with the data reporting up regulation of IL6 in stimulated MSCs. In the recent study, it has been suggested that immunosuppressive effects of MSCs can be through IL6 by inhibiting lymphocyte apoptosis. Their findings pointed out that MSCs inhibit apoptosis of lymphocytes, and that soluble factors, mainly IL6 secreted by MSCs after direct interaction with lymphocytes, play an important role in their anti-apoptotic function. In another report, IL6 mediated anti-apoptotic effects and drug-resistance mechanisms through both STAT3 and bcl-xL pathways in prostate cancer cells were revealed. In addition, it has been shown that MSCs suppress various immune functions through release of an immunosuppressive soluble factor, TGF-β1. Recently, we have shown that the co-cultivation of rat bone-marrow-MSCs with islets and STZ-damaged islets induce the expression of IL6 and TGF-β1 into the culture medium, besides the expression of the anti-apoptotic genes (Mapkapk2, Tnip1 and Bcl3) implying the cytoprotective, anti-inflammatory and anti-apoptotic effects of rBM-SCs through paracrine actions. This speech will focus on recent advances in the clarification of MSC properties and discussion of future perspectives.