Abstract
Mesenchymal stem cells promote the proliferation of hematopoietic stem/progenitor cells (HSPCs) and maintain stem cells in a primitive state. A previous study demonstrated the beneficial effects of placental/umbilical cord blood-derived mesenchymal stem cell-like stromal cells on the generation of both non-irradiated and X-irradiated HSPCsR). The present study examined the involvement of extracellular matrix components, which regulate the proliferation and differentiation of HSPCs, in the regeneration of X-irradiated HSPCs in the co-culture system. The co-culture experiments were performed as described in a previous reportR). The concentration of the extracellular matrix components, hyaluronic acid and sulfated glycosaminoglycans, contained in the conditioned media was assessed by an ELISA kit. The total number of cells and of lineage-committed myeloid hematopoietic progenitor cells generated in the co-culture of both non-irradiated and X-irradiated cells with stromal cells was significantly higher than those in the stroma-free culture supplemented with IL-3 plus SCF plus TPO. In addition, the number of CD34+ cells, CD34+/CD38- cells, and immature HSPCs were also increased more than in the stroma-free culture. The hematopoiesis observed in the co-culture was equivalent to that when the cytokines were added 16 h later, although a dramatic decrease was seen in the stroma-free culture. The co-culture produced hyaluronic acid and sulfated glycosaminoglycan. In particular, X-irradiated cells alone produced levels of higher sulfated glycosaminoglycan than the non-irradiated control culture and this production was up-regulated by the stroma cells. These results suggest that the cell-cell interactions play a critical role in the co-culture system. Furthermore, the extracellular matrix components also act as a key factor in the regeneration of myeloid hematopoietic progenitor cells from X-irradiated HSCs in the co-culture system.
R) Life Sci. 84: 598 (2009).
