Exp Mol Med.  2010 Feb;42(2):122-131. 10.3858/emm.2010.42.2.014.

Intramarrow injection of beta-catenin-activated, but not naive mesenchymal stromal cells stimulates self-renewal of hematopoietic stem cells in bone marrow

• Ahn JY
• Park G
• Shim JS
• Lee JW
• Oh IH

• KMID: 983985
• DOI: http://doi.org/10.3858/emm.2010.42.2.014

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.

Keyword

bone marrow; bone marrow transplantation; hematopoietic stem cells; stem cell niche; stromal cells

MeSH Terms

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