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Impact of maturational status on the ability of osteoblasts to enhance the hematopoietic function of stem and progenitor cells
Author(s) -
Cheng YingHua,
Chitteti Brahmananda R,
Streicher Drew A,
Morgan Joseph A,
RodriguezRodriguez Sonia,
Carlesso Nadia,
Srour Edward F,
Kacena Melissa A
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.302
Subject(s) - haematopoiesis , progenitor cell , stem cell , andrology , biology , cell culture , microbiology and biotechnology , hematopoietic stem cell , ex vivo , in vivo , immunology , genetics , medicine
Osteoblasts (OBs) exert a prominent regulatory effect on hematopoietic stem cells (HSCs). We evaluated the difference in hematopoietic expansion and function in response to co‐culture with OBs at various stages of development. Murine calvarial OBs were seeded directly (fresh) or cultured for 1, 2, or 3 weeks prior to seeding with 1000 Lin‐Sca1 + cKit+ (LSK) cells for 1 week. Significant increases in the following hematopoietic parameters were detected when comparing co‐cultures of fresh OBs to co‐cultures containing OBs cultured for 1, 2, or 3 weeks: total hematopoietic cell number (up to a 3.4‐fold increase), total colony forming unit (CFU) number in LSK progeny (up to an 18.1‐fold increase), and percentage of Lin‐Sca1+ cells (up to a 31.8‐fold increase). Importantly, these studies were corroborated by in vivo reconstitution studies in which LSK cells maintained in fresh OB co‐cultures supported a significantly higher level of chimerism than cells maintained in co‐cultures containing 3‐week OBs. Characterization of OBs cultured for 1, 2, or 3 weeks with real‐time PCR and functional mineralization assays showed that OB maturation increased with culture duration but was not affected by the presence of LSK cells in culture. Linear regression analyses of multiple parameters measured in these studies show that fresh, most likely more immature OBs better promote hematopoietic expansion and function than cultured, presumably more mature OBs and suggest that the hematopoiesis‐enhancing activity is mediated by cells present in fresh OB cultures de novo. © 2011 American Society for Bone and Mineral Research.