SDF-1/CXCL12 enhances in vitro replating capacity of murine and human multipotential and macrophage progenitor cells.
Hematopoietic progenitor cells (HPCs) manifest a limited self-renewal capacity, as determined by a surrogate assay involving replating capacity of single colonies in vitro with generation of secondary colonies. Stromal cell-derived factor-1 (SDF-1/CXCL12), has been implicated in regulation of hematopoiesis through its modulation of hematopoietic stem cell (HSC) and HPC migration, homing, mobilization, and survival. We used bone marrow cells from SDF-1/CXCL12 transgenic and littermate control mice, and culture of normal mouse bone marrow and human cord blood cells plated in the presence or absence of recombinant SDF-1/CXCL12 to evaluate a role for SDF-1/CXCL12 in the replating capability in vitro of multipotential [colony-forming units (CFU)-GEMM] and macrophage (CFU-M) progenitor cells. Competitive repopulating capacity of mouse HSCs was assessed in lethally irradiated mice. Transgenic or exogenous SDF-1/CXCL12 significantly enhanced numbers of secondary colonies formed from primary CFU-GEMM or CFU-M colonies. In the limited setting of our in vivo studies, the SDF-1/CXCL12 transgene did not influence HSC competitive repopulation. However, the results suggest that SDF-1/CXCL12 enhances in vitro replating/self-renewal of HPCs, which may contribute to myelopoiesis in vivo. This information may be of value to ex vivo expansion of HPCs/HSCs.
Broxmeyer
Hal E
HE
Department of Microbiology and Immunology, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA. hbroxmey@iupui.edu
Mejia
Jorge Alejandro Henao
JA
Hangoc
Giao
G
Barese
Cecilia
C
Dinauer
Mary
M
Cooper
Scott
S
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D005312:Fetal Blood / Q000166:cytology / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology