Intramarrow injection of beta-catenin-activated, but not naive mesenchymal stromal cells stimulates self-renewal of hematopoietic stem cells in bone marrow.
Bone marrow mesenchymal stromal cells (MSCs) have been implicated in the microenvironmental support of hematopoietic stem cells (HSCs) and often co-transplanted with HSCs to facilitate recovery of ablated bone marrows. However, the precise effect of transplanted MSCs on HSC regeneration remains unclear because the kinetics of HSC self-renewal in vivo after co-transplantation has not been monitored. In this study, we examined the effects of intrafemoral injection of MSCs on HSC self-renewal in rigorous competitive repopulating unit (CRU) assays using congenic transplantation models in which stromal progenitors (CFU-F) were ablated by irradiation. Interestingly, naïve MSCs injected into femur contributed to the reconstitution of a stromal niche in the ablated bone marrows, but did not exert a stimulatory effect on the in-vivo self-renewal of co-transplanted HSCs regardless of the transplantation methods. In contrast, HSC self-renewal was four-fold higher in bone marrows intrafemorally injected with beta-catenin-activated MSCs. These results reveal that naive MSCs lack a stimulatory effect on HSC self-renewal in-vivo and that stroma must be activated during recoveries of bone marrows. Stromal targeting of wnt/beta-catenin signals may be a strategy to activate such a stem cell niche for efficient regeneration of bone marrow HSCs.
Ahn
Ji Yeon
JY
Catholic High-Performance Cell Therapy Center, Department of Cellular Medicine, Seoul 137-040, Korea.
Park
Gyeongsin
G
Shim
Jae Seung
JS
Lee
Jong Wook
JW
Oh
Il Hoan
IH
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D012038:Regeneration; D055153:Stem Cell Niche / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D019172:Transplantation Conditioning; D051176:beta Catenin / Q000378:metabolism*
D051176:beta Catenin