Immunogenicity of pluripotent stem cells and their derivatives.
Immunogenicity of pluripotent stem cells and their derivatives.
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DOI：
10.1161/circresaha.111.249243
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发表时间：
2013-02-01
影响因子：
20.1
通讯作者：
Wu JC
中科院分区：
文献类型：
--
作者：
de Almeida PE;Ransohoff JD;Nahid A;Wu JC
多能干细胞具有自我更新和分化为各种类型体细胞的能力，为再生医学和人类健康带来了广阔的前景。然而，在临床应用之前，需要进行大量的转化研究，以确保它们的治疗后代是功能性和非致瘤性的，它们是稳定的，不会去分化，并且不会引发可能威胁其体内生存的免疫反应。因此，深入了解它们的生物学、遗传和表观遗传组成，以及它们的抗原库，对于预测它们的免疫原性和制定确保成功长期植入所需的策略至关重要。最近，重编程体细胞将为个性化医疗提供自体细胞治疗的期望受到了质疑。诱导多能干细胞（iPS）在体内表现出多种遗传和表观遗传异常，可促进致瘤性和免疫原性。了解iPS细胞衍生物中这些异常的持久性和影响对于临床医生预测移植后移植物的命运，并采取必要的措施防止免疫排斥至关重要。随着多能干细胞治疗的临床试验即将到来，进一步强调了理解免疫屏障并设计安全有效的策略来绕过它们的重要性。这种克服干细胞治疗免疫障碍的方法可以利用几十年来造血干细胞移植获得的有效知识。
The ability of pluripotent stem cells to self-renew and differentiate into all somatic cell types brings great prospects to regenerative medicine and human health. However, prior to clinical applications, much translational research is required to ensure that their therapeutic progenies are functional and non-tumorigenic, that they are stable and do not de-differentiate, and that they do not elicit immune responses that could threaten their survival in vivo. For this, an in-depth understanding of their biology, genetic and epigenetic makeup, and their antigenic repertoire is critical for predicting their immunogenicity and for developing strategies needed to assure successful long-term engraftment. More recently, the expectation that reprogrammed somatic cells would provide an autologous cell therapy for personalized medicine has been questioned. Induced pluripotent stem (iPS) cells display several genetic and epigenetic abnormalities that could promote tumorigenicity and immunogenicity in vivo. Understanding the persistence and effects of these abnormalities in iPS cell derivatives is critical to allow clinicians to predict graft fate following transplantation, and to take requisite measures to prevent immune rejection. With clinical trials of pluripotent stem cell therapy on the horizon, the importance of understanding immunological barriers and devising safe, effective strategies to bypass them is further underscored. This approach to overcome immunological barriers to stem cell therapy can take advantage of the validated knowledge acquired from decades of hematopoietic stem cell transplantation.