Kagimoto Shintaro, Takebe Takanori, Kobayashi Shinji, Yabuki Yuichiro, Hori Ayaka, Hirotomi Koichi, Mikami Taro, Uemura Toshimasa, Maegawa Jiro, Taniguchi Hideki
Department of Plastic and Reconstructive Surgery, Yokohama City University Hospital, Yokohama, Kanagawa, Japan.
Cell Transplant. 2016;25(5):951-62. doi: 10.3727/096368916X690917. Epub 2016 Feb 15.
We recently developed a promising regenerative method based on the xenotransplantation of human cartilage progenitor cells, demonstrating self-renewing elastic cartilage reconstruction with expected long-term tissue restoration. However, it remains unclear whether autotransplantation of cartilage progenitors may work by a similar principle in immunocompetent individuals. We used a nonhuman primate (monkey) model to assess the safety and efficacy of our regenerative approach because the model shares characteristics with humans in terms of biological functions, including anatomical features. First, we identified the expandable and multipotent progenitor population from monkey ear perichondrium and succeeded in inducing chondrocyte differentiation in vitro. Second, in vivo transplanted progenitor cells were capable of reconstructing elastic cartilage by xenotransplantation into an immunodeficient mouse. Finally, the autologous monkey progenitor cells were transplanted into the subcutaneous region of a craniofacial section and developed mature elastic cartilage of their own 3 months after transplantation. Furthermore, we attempted to develop a clinically relevant, noninvasive monitoring method using magnetic resonance imaging (MRI). Collectively, this report shows that the autologous transplantation of cartilage progenitors is potentially effective for reconstructing elastic cartilage. This principle will be invaluable for repairing craniofacial injuries and abnormalities in the context of plastic and reconstructive surgery.
我们最近开发了一种基于人软骨祖细胞异种移植的有前景的再生方法,证明了具有预期长期组织修复效果的自我更新弹性软骨重建。然而,在免疫功能正常的个体中,软骨祖细胞的自体移植是否通过类似原理起作用仍不清楚。我们使用非人类灵长类动物(猴子)模型来评估我们的再生方法的安全性和有效性,因为该模型在包括解剖特征在内的生物学功能方面与人类有共同特点。首先,我们从猴耳软骨膜中鉴定出可扩增且具有多能性的祖细胞群体,并成功在体外诱导软骨细胞分化。其次,体内移植的祖细胞能够通过异种移植到免疫缺陷小鼠体内来重建弹性软骨。最后,将自体猴祖细胞移植到颅面部切片的皮下区域,移植3个月后发育出自身的成熟弹性软骨。此外,我们尝试开发一种使用磁共振成像(MRI)的临床相关非侵入性监测方法。总体而言,本报告表明软骨祖细胞的自体移植对重建弹性软骨可能有效。这一原理对于修复整形和重建手术中的颅面部损伤及异常将具有重要价值。