Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892–4370, USA.
J Tissue Eng Regen Med. 2013 Mar;7(3):226-35. doi: 10.1002/term.515. Epub 2011 Nov 3.
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.
自体骨髓基质细胞(BMSCs)移植已成功用于骨重建。然而,为了将这种方法推进到骨组织工程的主流,BMSC 培养和移植的条件必须得到优化。在最近的一份报告中,用地塞米松(Dex)培养显著增加了体内人 BMSCs 的成骨作用。基于这一重要结论,我们分析了我们实验室积累的数据,其中常规使用含有或不含有两种成骨补充剂的培养基来生成人 BMSCs:地塞米松 10(-8)m 和抗坏血酸磷酸盐(AscP)10(-4)m。我们的数据表明,对于 22/24 位供体,用 Dex/AscP 培养和不培养的 BMSC 株在体内形成相似数量的骨。因此,人 BMSCs 似乎不需要在移植前在体外诱导成骨分化。同样,对于 12/14 位供体,用 Dex/AscP 培养和不培养的 BMSC 株形成造血区的程度相当。虽然 Dex/AscP 没有增加骨形成,但它们显著刺激了 BMSC 的体外增殖,而不影响成纤维细胞集落形成单位形成的 BMSC 集落数量。我们的结论是,对于绝大多数供体,Dex/AscP 对 BMSCs 在体内形成骨和骨髓支持基质的能力没有影响。然而,由于 BMSC 增殖增加,用 Dex/AscP 培养后从单个骨髓样本中获得的总成骨细胞群体比不培养时更大。由于 BMSC 增殖增加,Dex/AscP 可能会刺激骨形成,如果 BMSCs 和/或移植系统不理想的话。发表于 2011 年。本文是美国政府的工作,在美国属于公有领域。