A chimeric feeder comprising transforming growth factor beta 1‐ and basic fibroblast growth factor‐primed bone marrow‐derived mesenchymal stromal cells suppresses the expansion of hematopoietic stem and progenitor cells

Bone marrow-derived mesenchymal stromal cells (BMSCs) physically associate with the hematopoietic stem cells (HSCs), forming a unique HSC niche. Owing to this proximity, the signaling mechanisms prevailing in the BMSCs affect the fate of the HSCs. In addition to cell-cell and cell-extracellular matrix interactions, various cytokines and growth factors present in the BM milieu evoke signaling mechanisms in the BMSCs. Previously, I have shown that priming of human BMSCs with transforming growth factor beta 1 (TGF beta 1), a cytokine consistently found at active sites of hematopoiesis, boosts their hematopoiesis-supportive ability. Basic fibroblast growth factor (bFGF), another cytokine present in the marrow microenvironment, positively regulates hematopoiesis. Hence, I examined whether priming human BMSCs with bFGF improves their hematopoiesis-supportive ability. I found that bFGF-primed BMSCs stimulate hematopoiesis, as seen by a significant increase in colony formation from the bone marrow cells briefly interacted with them and the extensive proliferation of CD34(+) HSCs cocultured with them. However, contrary to my expectation, I found that chimeric feeders comprising a mixture of TGF-primed and bFGF-primed BMSCs exerted a suppressive effect. These data demonstrate that though the TGF- and bFGF-primed BMSCs exert a salutary effect on hematopoiesis when used independently, they exert a suppressive effect when presented as a chimera. These findings suggest that the combinatorial effect of various priming agents and cytokines on the functionality of BMSCs toward the target tissues needs to be critically evaluated before they are clinically applied.