Rerouting mesenchymal stem cell trajectory towards epithelial lineage by engineering cellular niche

Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a promising outcome in the field of regenerative medicine. MSCs are present in various tissues including bone marrow, fat, skin, and placenta. The interest in clinical application of these mesoderm-derived MSCs is primarily fueled by their high self-renewal capacity and multipotency. Although, early studies indicated limited differentiation capacity of MSCs into same cell lineages from which they were isolated, subsequent investigations showed differentiation potential into other cell types of mesoderm origin including osteoblasts, adipocytes, fibroblasts, cardiomyocytes, and chondrocytes. Furthermore, MSCs exhibit a remarkable feature of transdifferentiation into ectodermal, neuroectodermal, and endodermal cells, phenomena referred to as ‘stem cell plasticity’. This opened the possibility of clinical applications of MSCs in the regeneration of other tissues like corneal reconstruction, treatment of acute lung injury, oral mucosal regeneration, homing of MSCs for regeneration at sites of injury etc. Though several evidence have accrued demonstrating this phenomenon, there is still a gap in understanding the molecular mechanism of such transitions which will be important to efficiently control the process. Interestingly, the process can be drawn a parallel with the Mesenchymal to Epithelial Transitions (MET) that takes place inside the body during embryonic development or certain pathophysiological conditions. In this review, a brief attempt is first made to understand the evidence of MSC transdifferentiation based on the current knowledge about MET. We then specifically focus on systematic presentation and analysis of the microenvironment factors involved in MSC transdifferentiation to epithelial lineages which would have applications in regenerative medicine.