Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400015, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Oral Implantology, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Acta Biomater. 2018 Jul 1;74:222-235. doi: 10.1016/j.actbio.2018.05.028. Epub 2018 May 18.
Induced pluripotent stem cells (iPSCs) are regarded as a new cell source for regenerative medicine. Recent advances in tissue engineering have brought to light the therapeutic application of induced pluripotent stem cells (iPSCs) in bone defect repair. However, a safe and efficient way to differentiate iPSCs into osteogenic lineage remains to be a major challenge. Here we describe an approach using anti-BMP2 antibodies (Abs) to mediate osteogenic differentiation of iPSC-derived mesenchymal stromal cells (iMSCs). We first proved that 3G7 (an anti-BMP2 Ab) not only bound to BMP2, but also allowed the bound BMP2 to engage the BMP2 receptors on iMSCs. Subcutaneous implantation sites loaded with iMSCs + 3G7 group showed significant bone formation and vascularization in mice while those sites with exogenous BMP2 exhibited dystrophic calcification and significantly lower vascularization. Our in vitro study demonstrated that the anti-BMP2 Ab/BMP2 immune complex were capable of dictating the acquisition of osteogenic phenotype of iMSCs and subsequent mineralization. The study provided the first evidence of antibody-mediated differentiation of iMSCs and osseous regeneration in vivo. This novel strategy takes full advantage of the endogenous bioactive molecules for osseous regeneration and its potential therapeutic application is promising.
Induced pluripotent stem cells (iPSCs) and its derived cells hold significant promise for the treatment of bone defects. In present study, we carried out the concept of antibody-mediated bone regeneration into the iPSC research for the first time. We demonstrated that anti-BMP2 Ab/BMP2 immune complex was capable of promoting osteogenic differentiation of iPSC-derived MSCs (iMSCs), likely through the classical BMP2/Smad1/Runx2 pathway. Subcutaneous co-delivery of iMSCs and anti-BMP2 Abs resulted in significant bone formation and vascularization. These findings suggested antibody mediated osteogenic differentiation may be a favorable approach for iPSC-based bone tissue engineering.
诱导多能干细胞（iPSCs）被视为再生医学的新细胞来源。组织工程学的最新进展揭示了诱导多能干细胞（iPSCs）在骨缺损修复中的治疗应用。然而，将 iPSCs 安全有效地分化为成骨谱系仍然是一个主要挑战。在这里，我们描述了一种使用抗 BMP2 抗体（Abs）来介导 iPSC 衍生的间充质基质细胞（iMSCs）成骨分化的方法。我们首先证明 3G7（一种抗 BMP2 Ab）不仅与 BMP2 结合，而且还允许结合的 BMP2 与 iMSCs 上的 BMP2 受体结合。皮下植入部位负载 iMSCs+3G7 组的小鼠表现出明显的骨形成和血管生成，而那些部位外源性 BMP2 表现出营养不良性钙化和明显较低的血管生成。我们的体外研究表明，抗 BMP2 Ab/BMP2 免疫复合物能够决定 iMSCs 获得成骨表型和随后的矿化。该研究首次提供了抗体介导的 iMSCs 分化和体内骨再生的证据。这种新策略充分利用了内源性生物活性分子进行骨再生，其潜在的治疗应用前景广阔。
诱导多能干细胞（iPSCs）及其衍生细胞在治疗骨缺损方面具有重要意义。在本研究中，我们首次将抗体介导的骨再生概念引入 iPSC 研究。我们证明抗 BMP2 Ab/BMP2 免疫复合物能够促进 iPSC 衍生的间充质基质细胞（iMSCs）的成骨分化，可能通过经典的 BMP2/Smad1/Runx2 途径。iMSCs 和抗 BMP2 Abs 的皮下共递送导致了明显的骨形成和血管生成。这些发现表明，抗体介导的成骨分化可能是一种基于 iPSC 的骨组织工程的有利方法。
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