Cell Rep:黑素脱失患者来源多能性干细胞的自体移植治疗 -色素恢复与皮肤功能重建取得重大突破

2019-04-10 不详 细胞

近日,Cell Reports公布了一项皮肤再生医学研究领域的重要进展:《患者iPS细胞来源的诱导黑素细胞在自体移植治疗中的潜能》(Therapeutic potential of patient iPSC-derived iMelanocytes in autologoustransplantation)。

近日,Cell Reports公布了一项皮肤再生医学研究领域的重要进展:《患者iPS细胞来源的诱导黑素细胞在自体移植治疗中的潜能》(Therapeutic potential of patient iPSC-derived iMelanocytes in autologoustransplantation)。

黑素细胞的数量减少或功能缺失将引起色素脱失性疾病,如白癜风等。由于影响美观,患者易产生抑郁、焦虑等不良情绪,导致生活质量下降,严重者可伴发精神心理疾病,影响学习、工作和社交等社会性功能。黑素细胞自体移植是治疗白癜风的有效方法之一,但通常较难获取足够数量、保持较高增殖活性并适合移植的黑素细胞。日本诺贝尔奖获得者山中伸弥教授发明的诱导多能性干细胞(即iPS细胞)具有无限增殖潜能和多向分化能力,在再生医学的移植治疗领域具有广阔的应用前景,然而多能性干细胞诱导分化而来的黑素细胞在体内的组织再构建能力和安全性问题此前尚未获得有效验证。

本研究利用白癜风患者色素脱失部位的皮肤细胞生成自体iPS细胞,通过高效独特的三维诱导分化培养技术获得了大量具有高增殖能力和体内整合功能的黑素细胞。转录组测序分析表明,与正常黑素细胞相比,患者iPS来源的诱导黑素细胞可能涉及白癜风发病机制相关的多个信号通路。为了验证这些细胞在体内移植后的功能维持,本研究借助免疫缺陷鼠的毛囊重构模型,证实iPS细胞来源的黑素干细胞和成熟黑素细胞可以分别整合至小鼠毛囊的隆凸部和毛球部,同时将黑素颗粒正常传递并生成黑色毛囊,其整合效率高于普通成熟黑素细胞。而这些整合部位为人类黑素干细胞和成熟黑素细胞的正常生理性分布区域。此外,iPS细胞来源黑素细胞在小鼠体内移植后的存活及功能维持可达7周以上,而在长达2个多月的观察期间,无致瘤性表现。

此项研究不仅首次揭示了iPS细胞来源的诱导黑素细胞在体内的长期功能性维持状况,也为今后个体化细胞移植治疗提供可靠的细胞源和治疗策略。此项成果的成功推广和积极临床转化,可为黑素脱失疾患带来革命性的治疗手段。更进一步,有关色素脱失的发病机制极其复杂,有遗传背景、氧化应激、药物反应等,本研究为将来揭示色素脱失的发病机制提供了可能的前所未有的研究模型,同时也为研究其他难治性疾患提供了可鉴之处。

原始出处:

Li-Ping Liu,et al.Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation.Cell Rep.VOLUME 27, ISSUE 2, P455-466.E5, APRIL 09, 2019

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    2019-06-20 sunylz
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    2019-10-14 维他命
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