Intramarrow injection of beta-catenin-activated, but not naive mesenchymal stromal cells stimulates self-renewal of hematopoietic stem cells in bone marrow.
10.3858/emm.2010.42.2.014
- Author:
Ji Yeon AHN
1
;
Gyeongsin PARK
;
Jae Seung SHIM
;
Jong Wook LEE
;
Il Hoan OH
Author Information
1. Catholic High-Performance Cell Therapy Center, Department of Cellular Medicine, The Catholic University of Korea, Seoul 137-040, Korea. iho@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
bone marrow;
bone marrow transplantation;
hematopoietic stem cells;
stem cell niche;
stromal cells
- MeSH:
Animals;
Bone Marrow/metabolism/pathology;
Hematopoietic Stem Cell Mobilization;
*Hematopoietic Stem Cell Transplantation;
Hematopoietic Stem Cells/pathology;
Mesenchymal Stem Cell Transplantation;
Mesenchymal Stem Cells/*metabolism/pathology;
Mice;
Mice, Inbred C57BL;
Radiation Chimera;
Regeneration;
Stem Cell Niche/metabolism/pathology;
Stromal Cells/*metabolism/pathology;
*Transplantation Conditioning;
beta Catenin/*metabolism
- From:Experimental & Molecular Medicine
2010;42(2):122-131
- CountryRepublic of Korea
- Language:English
-
Abstract:
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, naive 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.
