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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Engineered vascularized bone grafts
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Engineered vascularized bone grafts

机译：工程化血管移植骨

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摘要

Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neo-vascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. We used a mouse model to develop a two-stage protocol for generating vascularized bone grafts using mesenchymal stem cells (hMSCs) from human bone marrow and umbilical cord-derived endothelial cells. The endothe-lial cells formed tube-like structures and subsequently networks throughout the bone scaffold 4-7 days after implantation. hMSCs were essential for stable vasculature both in vitro and in vivo; however, contrary to expectations, vasculature derived from hMSCs briefly cultured in medium designed to maintain a proliferative, nondifferentiated state was more extensive and stable than that with hMSCs with a TGF-p-induced smooth muscle cell phenotype. Anastomosis occurred by day 11, with most hMSCs associating closely with the network. Although initially immature and highly permeable, at 4 weeks the network was mature. Initiation of scaffold mineralization had also occurred by this period. Some human-derived vessels were still present at 5 months, but the majority of the graft vasculature had been functionally remodeled with host cells. In conclusion, clinically relevant progenitor sources for peri-cytes and endothelial cells can serve to generate highly functional microvascular networks for tissue engineered bone grafts.
机译：临床方案利用骨髓来播种合成的和脱细胞的同种异体骨移植物，以增强支架的重塑和融合。骨髓来源的细胞因子在移植物表面诱导宿主新血管形成，但是低氧条件导致核心细胞死亡。产生广泛的原始神经丛样血管网络的细胞成分的添加会在吻合后灌注整个支架，从而可能产生明显更高质量的移植物。我们使用小鼠模型开发了一个两阶段协议，该协议使用人骨髓和脐带来源的内皮细胞的间充质干细胞（hMSCs）生成血管化的骨移植物。内皮细胞形成管状结构，并在植入后4-7天遍及整个骨支架网络。 hMSC对于体外和体内稳定的脉管系统都是必不可少的。然而，与预期相反，与具有TGF-β诱导的平滑肌细胞表型的hMSC相比，在设计用于维持增殖，未分化状态的培养基中短暂培养的hMSC的脉管系统更为广泛和稳定。第11天就发生了吻合，大多数hMSC与网络密切相关。尽管最初不成熟且具有高渗透性，但在4周后网络已经成熟。在此期间也发生了支架矿化的现象。在第5个月时仍存在一些人源性血管，但大多数移植血管已被宿主细胞功能性重塑。总之，临床上有关周细胞和内皮细胞的祖细胞可用于为组织工程化的骨移植物生成功能强大的微血管网络。

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    Olga Tsigkou; Irina Pomerantseva; Joel A. Spencer; Patricia A. Redondo; Alison R. Hart; Elisabeth ODoherty; Yunfeng Lin; Claudia C. Friedrich; Laurence Daheron; Charles P. Lin; Cathryn A. Sundback; Joseph P. Vacanti; Craig Neville;

  • 作者单位

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Biomedical Engineering, Tufts University, Science and Technology Center, 4 Colby Street, Medford, MA 02155;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Regenerative Medicine, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Surgery, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    endothelial cell; mesenchymal stem cell; pericyte; vasculogenesis;

    机译：内皮细胞间充质干细胞周细胞血管生成;

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