Preclinical Safety Evaluation of Allogeneic Induced Pluripotent Stem Cell-Based Therapy in a Swine Model of Myocardial Infarction.
Preclinical Safety Evaluation of Allogeneic Induced Pluripotent Stem Cell-Based Therapy in a Swine Model of Myocardial Infarction.
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在猪心肌梗死模型中同种异体诱导多能干细胞疗法的临床前安全性评估。
DOI：
10.1089/ten.tec.2017.0156
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
A. Bayés
中科院分区：
文献类型：
--
作者：
C. Gálvez;C. Soler;O. Iborra;I. Díaz;Mercè Martí;O. Iglesias;C. Prat;Verónica Crisóstomo;A. Llucià;I. Perea;S. Roura;F. Sánchez;Ángel Raya;A. Bayés
生物基质和诱导多能干细胞（iPSC）衍生物的组合，以帮助修复和心肌瘢痕形成可能很快成为心脏再生医学的现实。然而，与残余未分化细胞相关的肿瘤风险仍然是基于iPSC的疗法的重要安全性问题。这种担心在异种移植中没有得到令人满意的解决，异种移植需要对移植动物进行免疫抑制。在这项研究中，我们评估了在同种异体环境中移植未分化iPSC的安全性。鉴于猪通常用作心脏医学中的大型动物模型，我们使用猪iPSC（p-iPSC）与支持急性心肌梗死后恢复的生物工程构建体结合。组织学分析发现，在30天和90天的随访后，宿主心肌或生物基质内没有p-iPSC或p-iPSC衍生细胞的证据。与植入细胞的消失一致，我们无法观察到这些治疗在左心室射血分数、心输出量、心室容积或坏死方面的功能益处。因此，我们得出结论，至少在心脏再生医学的背景下，当在同种异体环境中用于具有免疫能力的受体时，残留的未分化的iPSC不应引起安全性问题。
The combination of biomatrices and induced pluripotent stem cell (iPSC) derivatives to aid repair and myocardial scar formation may soon become a reality for cardiac regenerative medicine. However, the tumor risk associated with residual undifferentiated cells remains an important safety concern of iPSC-based therapies. This concern is not satisfactorily addressed in xenotransplantation, which requires immune suppression of the transplanted animal. In this study, we assessed the safety of transplanting undifferentiated iPSCs in an allogeneic setting. Given that swine are commonly used as large animal models in cardiac medicine, we used porcine iPSCs (p-iPSCs) in conjunction with bioengineered constructs that support recovery after acute myocardial infarction. Histopathology analyses found no evidence of p-iPSCs or p-iPSC-derived cells within the host myocardium or biomatrices after 30 and 90 days of follow-up. Consistent with the disappearance of the implanted cells, we could not observe functional benefit of these treatments in terms of left ventricular ejection fraction, cardiac output, ventricular volumes, or necrosis. We therefore conclude that residual undifferentiated iPSCs should pose no safety concern when used on immune-competent recipients in an allogeneic setting, at least in the context of cardiac regenerative medicine.
诱导多能干（iPS）细胞修复和再生梗塞心肌。
影响因子：
4.9
作者：
Singla DK;Long X;Glass C;Singla RD;Yan B
通讯作者：
Yan B
影响因子：
4.6
作者：
Zhou, Yifu;Wang, Suna;Yu, Zuxi;Hoyt, Robert F., Jr.;Hunt, Timothy;Kindzelski, Bogdan;Shou, David;Xie, Wen;Du, Yubin;Liu, Chengyu;Horvath, Keith A.
通讯作者：
Horvath, Keith A.