Thrombospondin-1 promotes mesenchymal stromal cell functions via TGFβ and in cooperation with PDGF

摘要: Mesenchymal stromal cells (MSC) are characterized by unique tropism for wounded tissues, high differentiating capacity, ability to induce tissue repair, and anti-inflammatory immunoregulatory activities. This has generated interest in their therapeutic use severe human conditions as well regenerative medicine engineering. Identification of factors involved the regulation MSC proliferation, migration differentiation could provide insights into pathophysiological be exploited optimize clinical grade expansion protocols use. Here we identify thrombospondin-1 (TSP-1) a major regulator MSC. TSP-1 induced proliferation. effect was mediated TSP-1-induced activation endogenous TGFβ, shown inhibitory effects anti-TGFβ antibodies lack activity TSP-2 - that does not activate TGFβ. Moreover, strongly potentiated proliferative migratory PDGF on directly bound PDGF, through site located within type III repeats, protected growth factor from degradation MSC-derived proteases, hence increasing its stability bioavailability. The studies presented here more comprehensive picture pleiotropic behavior, setting basis further aimed at investigating possible vitro applications.