Lee Jin Saem, Lee Jeoung Eun, Yu Shin-Hye, Chun Taehoon, Chang Mi-Yoon, Lee Dong Ryul, Park Chang-Hwan
Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
CHA Advanced Research Institute, CHA University, Seongnam, Korea.
Int J Stem Cells. 2024 Feb 28;17(1):59-69. doi: 10.15283/ijsc23037. Epub 2023 Oct 26.
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 . 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.
人类多能干细胞(hPSCs),如人类胚胎干细胞(hESCs)、诱导多能干细胞和体细胞核移植(SCNT)-hESCs,能够永久自我更新,同时保持其分化为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,hPSCs在临床试验中的应用仍存在持续挑战,其中最显著的挑战之一是当移植来自异基因(非自身)细胞来源时,患者免疫系统因人类白细胞抗原(HLA)不匹配而产生的移植物排斥反应。纯合SCNT-hESCs(homo-SCNT-hESCs)被用于简化临床应用并减少HLA不匹配。在此,我们提出一种无动物成分方案,该方案证实了hPSCs中神经前体细胞的高效生成以及多巴胺能神经元的分化。此外,比较hESC、homo-SCNT-hESCs和异源SCNT-hESCs的HLA表达模式时没有差异。我们提出,可培养的hPSCs在分化能力和HLA表达方面没有差异。因此,预计在临床试验中,homo-SCNT-hESCs与神经前体细胞一起移植时将具有更广泛的应用。