Differential Activation of Ca Influx Channels Modulate Stem Cell Potency, Their Proliferation/viability and Tissue Regeneration

Stem cells have indefinite self-renewable capability; however, factors that modulate their pluripotency/function are not fully identified. Here we show that store-dependent Ca entry is essential for modulating the function of bone marrow-derived mesenchymal stem cells (MSCs). Increasing external Ca modulated cell cycle progression that was critical for MSCs survival. Additionally, Ca was critical for stem proliferation, its differentiation, and maintaining stem cell potential. Ca channel characterization, including gene silencing, showed two distinct Ca entry channels (through Orai1/TRPC1 or via Orai3) that differentially regulate the proliferation and viability of MSCs. Importantly, NFκB translocation, but not JNK/ERK into the nucleus, was observed upon store depletion, which was blocked by the addition of Ca channel inhibitors. Radiation lead to a decrease in saliva secretion, decrease in acinar cell number, and enlarged ducts were observed, which were restored by the transplantation of stem cells that were propagated in higher Ca. Finally radiation showed a decrese in TRPC1 expression along with a decrese in AQP5, which was again restored upon MSC tranplantation. Together these results suggest that Ca entry is essential for stem cell function that could be critical for regenerative medicine.