Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells.
The stromal vascular fraction (SVF) in adipose tissue contains a pool of various stem and progenitor cells, but the existence of hematopoietic stem and progenitor cells (HSPCs) in the SVF has not been seriously considered. We detected the presence of HSPCs in the SVF by phenotypically probing with Lin(-)Sca-1(+)c-kit(+) (LSK) and functionally confirming the presence using colony-forming cell assay and assessing the long-term multilineage reconstitution ability after SVF transplantation. The LSK population in the SVF was 0.004% plus or minus 0.001%, and 5 x 10(5) freshly isolated SVF cells gave rise to 13 plus or minus 4 multilineage colonies. In addition, 0.15% plus or minus 0.03% of SVF cells was home to bone marrow (BM), especially near vascular and endosteal regions, 24 hours after blood transplantation. SVF transplantation was capable of generating a long-term (> 16 weeks), but variable extent (2.1%-32.1%) multilineage reconstitution in primary recipients, which was subsequently transferred to the secondary recipients by BM transplantation. All HSPCs within the SVF originated from the BM. Furthermore, the granulocyte-colony-stimulating factor (G-CSF) mobilization of HSPCs from BM markedly elevated the number of phenotypic and functional HSPCs in the SVF, which induced a high efficiency long-term reconstitution in multilineage hematopoiesis in vivo. Our results provide compelling evidence that adipose tissue is a novel extramedullary tissue possessing phenotypic and functional HSPCs.
Han
Jinah
J
National Research Laboratory of Vascular Biology and Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Koh
Young Jun
YJ
Moon
Hye Rin
HR
Ryoo
Hyun Gee
HG
Cho
Chung-Hyun
CH
Kim
Injune
I
Koh
Gou Young
GY
D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016130:Immunophenotyping; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D016179:Granulocyte Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit