title: In vivo formation of bone and haematopoietic territories by transplanted human bone marrow stromal cells generated in medium with and without osteogenic supplements.
abstract: Autologous transplantation of human bone marrow stromal cells (BMSCs) has been successfully used for bone reconstruction. However, in order to advance this approach into the mainstream of bone tissue engineering, the conditions for BMSC cultivation and transplantation must be optimized. In a recent report, cultivation with dexamethasone (Dex) significantly increased bone formation by human BMSCs in vivo. Based on this important conclusion, we analysed the data accumulated by our laboratory, where human BMSCs have been routinely generated using media both with and without a combination of two osteogenic supplements: Dex at 10(-8)  m and ascorbic acid phosphate (AscP) at 10(-4)  m. Our data demonstrate that for 22/24 donors, BMSC strains propagated with and without Dex/AscP formed similar amounts of bone in vivo. Thus, human BMSCs do not appear to need to be induced to osteogenic differentiation ex vivo prior to transplantation. Similarly, for 12/14 donors, BMSC strains cultured with and without Dex/AscP formed haematopoietic territories to a comparable extent. While Dex/AscP did not increase bone formation, they significantly stimulated BMSC in vitro proliferation without affecting the number of BMSC colonies formed by the colony-forming units-fibroblasts. We conclude that for the substantial majority of donors, Dex/AscP have no effect on the ability of BMSCs to form bone and myelosupportive stroma in vivo. However, due to increased BMSC proliferation, the total osteogenic population obtained from a single marrow sample is larger after cultivation with Dex/AscP than without them. Secondary to increased BMSC proliferation, Dex/AscP may stimulate bone formation if BMSCs and/or the transplantation system are less than optimal. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.
authors: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892–4370, USA. skuznets@mail.nih.gov
authors: Sergei A
authors: SA
authors: Kuznetsov
authors: Mahesh H
authors: MH
authors: Mankani
authors: Pamela Gehron
authors: PG
authors: Robey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D003470:Culture Media / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D055815:Young Adult
chemical_list: D003470:Culture Media; D003907:Dexamethasone; D001205:Ascorbic Acid