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Expression of Major Histocompatibility Complex during Neuronal Differentiation of Somatic Cell Nuclear Transfer-Human Embryonic Stem Cells.
International Journal of Stem Cells ( IF 2.3 ) Pub Date : 2023-10-26 , DOI: 10.15283/ijsc23037
Jin Saem Lee 1 , Jeoung Eun Lee 2 , Shin-Hye Yu 1, 3 , Taehoon Chun 4 , Mi-Yoon Chang 5, 6, 7 , Dong Ryul Lee 2, 8 , Chang-Hwan Park 1, 7
Affiliation  

Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured in vitro. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.

中文翻译:

体细胞核移植-人胚胎干细胞神经元分化过程中主要组织相容性复合物的表达。

人类多能干细胞(hPSC),例如人类胚胎干细胞(hESC)、诱导多能干细胞和体细胞核移植(SCNT)-hESC可以永久自我更新,同时保持分化成任何类型体细胞的能力,从而成为细胞治疗的重要细胞来源。然而,hPSC 在临床试验中的应用始终存在挑战,其中最重要的挑战之一是当从同种异体(非自体)获得移植物时,患者免疫系统响应人类白细胞抗原(HLA)不匹配而产生移植排斥。 )细胞来源。使用纯合SCNT-hESCs(homo-SCNT-hESCs)来简化临床应用并减少HLA不匹配。在这里,我们提出了一种无异源协议,证实了 hPSC 中神经前体细胞的有效生成以及多巴胺能神经元的分化。此外,比较 hESC、同源 SCNT-hESC 和异源 SCNT-hESC 的 HLA 表达模式没有差异。我们认为体外培养的 hPSC 的分化能力和 HLA 表达没有差异。因此,预计同源SCNT-hESCs在临床试验中与神经前体细胞移植后将具有更广泛的应用。
更新日期:2023-10-26
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