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首页> 外文期刊>Journal of tissue engineering and regenerative medicine >Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis
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Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis

机译：大型动物模型开发的间充质基质细胞疗法的临床翻译，两种案例研究对萎缩伪关

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Pseudoarthrosis is a relatively frequent complication of fractures, in which the lack of mechanical stability and biological stimuli results in the failure of bone union, most frequently in humerus and tibia. Treatment of recalcitrant pseudoarthrosis relies on the achievement of satisfactory mechanical stability combined with adequate local biology. Herein we present two cases of atrophic pseudoarthrosis that received a tissue-engineering product (TEP) composed of autologous bone marrow-derived mesenchymal stromal cells (BM-MSC) combined with deantigenized trabecular bone particles from a tissue bank. The feasibility of the treatment and osteogenic potential of the cell-based medicine was first demonstrated in an ovine model of critical size segmental tibial defect. Clinical-grade autologous BM-MSC were produced following a good manufacturing practice-compliant bioprocess. Results were successful in one case, with pseudoarthrosis resolution, and inconclusive in the other one. The first patient presented atrophic pseudoarthrosis of the humeral diaphysis and was treated with osteosynthesis and TEP resulting in satisfactory consolidation at month 6. The second case presented a recalcitrant pseudoarthrosis of the proximal tibia and the Masquelet technique was followed before filling the defect with the TEP. This patient presented a neuropathic pain syndrome unrelated to the treatment that forced the amputation of the extremity 3months later. In this case, the histological analysis of the tissue formed at the defect site provided evidence of neovascularization but no overt bone remodelling activity. It is concluded that the use of expanded autologous BM-MSC to treat pseudoarthrosis was demonstrated to be feasible and safe, provided that no clinical complications were reported, and early signs of effectiveness were observed. Copyright (C) 2016 John Wiley & Sons, Ltd.
机译：假期关节症是骨折的相对频繁的复杂性，其中缺乏机械稳定性和生物刺激导致骨髓愈合的失败，最常见于肱骨和胫骨。顽固性伪关的治疗依赖于实现令人满意的机械稳定性与充足的局部生物学结合。在本文中，我们呈现了两种萎缩伪关，接受由自体骨髓衍生的间充质基质细胞（BM-MSC）组成的组织 - 工程产品（TEP）与来自组织群的Deantigenized Trabecular骨颗粒组成。首先在临界大小胫骨缺陷的绵延模型中证明了细胞基医学治疗和骨质发生潜力的可行性。在符合良好的制造实践的生物过程之后生产临床级自体BM-MSC。结果在一个案例中成功，具有伪育分辨率，另一个案例，另一个案例尚无定论。第一个患者呈现肱骨骨干的萎缩假性，并用骨质合成和Tep治疗，在月6月份导致令人满意的固结。第二种情况呈现近端胫骨的顽固性假期，并在填充TEP缺陷之前呈现副型技术。该患者呈现出一种与治疗无关的神经疗法疼痛综合征，以便以后迫使肢体截肢。在这种情况下，在缺陷部位形成的组织的组织学分析提供了新生血管化的证据，但没有明显的骨改造活性。得出结论是，使用扩增的自体BM-MSC治疗假性关节症是可行和安全的，条件是没有报道临床并发症，并且观察到早期的有效性迹象。版权所有（c）2016 John Wiley＆Sons，Ltd。

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