SDF-1/CXCL12 enhances in vitro replating capacity of murine and human multipotential and macrophage progenitor cells

• Published in: Stem cells and development Vol. 16; no. 4; p. 589
• Main Authors: Broxmeyer, Hal E, Mejia, Jorge Alejandro Henao, Hangoc, Giao, Barese, Cecilia, Dinauer, Mary, Cooper, Scott
• Format: Journal Article
• Language: English
• Published: United States 01.08.2007
• Subjects: Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Cell Division - physiology; Chemokine CXCL12 - metabolism; Colony-Forming Units Assay; Fetal Blood - cytology; Fetal Blood - physiology; Humans; In Situ Hybridization, Fluorescence; Macrophages - cytology; Macrophages - physiology; Mice; Mice, Transgenic; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - physiology; Stem Cells - cytology; Stem Cells - physiology; Stromal Cells - physiology
• ISSN: 1547-3287
• DOI: 10.1089/scd.2007.0044

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.