Immunomodulation by mesenchymal stem cells during osteogenic differentiation: Clinical implications during bone regeneration.

Critical bone defects resulting in delayed and non-union are a major concern in the field of orthopedics. Over the past decade, mesenchymal stem cells (MSCs) have become a promising frontier for bone repair and regeneration owing to their high expansion rate and osteogenic differentiation potential ex vivo. MSCs have also long been associated with their ability to modulate immune response in the recipients. These can even skew the immune response towards pro-inflammatory or anti-inflammatory type by sensing their local microenvironment. MSCs adopt anti-inflammatory phenotype at bone injury site and secrete various immunomodulatory factors such as IDO, NO, TGFβ1 and PGE-2 which have redundant role in osteoblast differentiation and bone formation. As such, several studies have also sought to decipher the immunomodulatory effects of osteogenically differentiated MSCs. The present review discusses the immunomodulatory status of MSCs during their osteogenic differentiation and summarizes few mechanisms that cause immunosuppression by osteogenically differentiated MSCs and its implication during bone healing.