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人诱导多能干细胞来源的畸胎瘤中间充质干细胞用于骨软骨缺损再生的治疗潜力。

Therapeutic potential of mesenchymal stem cells from human iPSC-derived teratomas for osteochondral defect regeneration.

作者信息

Kim Jiseong, Kim Jin-Su, Kim Dohyun, Bello Alvin Bacero, Kim Byoung Ju, Cha Byung-Hyun, Lee Soo-Hong

机构信息

Department of Biomedical Technology Dongguk University Goyang-si Republic of Korea.

Department of Biomedical Science CHA University Seongnam-si Republic of Korea.

出版信息

Bioeng Transl Med. 2023 Nov 29;9(2):e10629. doi: 10.1002/btm2.10629. eCollection 2024 Mar.

DOI:10.1002/btm2.10629
PMID:38435815
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10905541/
Abstract

Human induced pluripotent stem cells (iPSCs) hold great promise for personalized medicine, as they can be differentiated into specific cell types, especially mesenchymal stem cells (MSCs). Therefore, our study sought to assess the feasibility of deriving MSCs from teratomas generated from human iPSCs. Teratomas serve as a model to mimic multilineage human development, thus enriching specific somatic progenitors and stem cells. Here, we discovered a small, condensed mass of MSCs within iPSC-generated teratomas. Afterward, we successfully isolated MSCs from this condensed mass, which was a byproduct of teratoma development. To evaluate the characteristics and cell behaviors of iPSC-derived MSCs (iPSC-MSCs), we conducted comprehensive assessments using qPCR, immunophenotype analysis, and cell proliferation-related assays. Remarkably, iPSC-MSCs exhibited an immunophenotype resembling that of conventional MSCs, and they displayed robust proliferative capabilities, similar to those of higher pluripotent stem cell-derived MSCs. Furthermore, iPSC-MSCs demonstrated the ability to differentiate into multiple lineages in vitro. Finally, we evaluated the therapeutic potential of iPSC-MSCs using an osteochondral defect model. Our findings demonstrated that teratomas are a promising source for the isolation of condensed MSCs. More importantly, our results suggest that iPSC-MSCs derived from teratomas possess the capacity for tissue regeneration, highlighting their promise for future therapeutic applications.

摘要

人类诱导多能干细胞(iPSC)在个性化医疗方面具有巨大潜力,因为它们可以分化为特定的细胞类型,尤其是间充质干细胞(MSC)。因此,我们的研究旨在评估从人iPSC产生的畸胎瘤中获取MSC的可行性。畸胎瘤可作为模拟人类多谱系发育的模型,从而富集特定的体细胞祖细胞和干细胞。在此,我们在iPSC产生的畸胎瘤中发现了一小团浓缩的MSC。随后,我们成功地从这团浓缩物中分离出了MSC,这是畸胎瘤发育的一个副产品。为了评估iPSC来源的MSC(iPSC-MSC)的特性和细胞行为,我们使用qPCR、免疫表型分析和细胞增殖相关检测进行了全面评估。值得注意的是,iPSC-MSC表现出与传统MSC相似的免疫表型,并且它们具有强大的增殖能力,类似于更高多能干细胞来源的MSC。此外,iPSC-MSC在体外表现出分化为多个谱系的能力。最后,我们使用骨软骨缺损模型评估了iPSC-MSC的治疗潜力。我们的研究结果表明,畸胎瘤是分离浓缩MSC的一个有前景的来源。更重要的是,我们的结果表明,源自畸胎瘤的iPSC-MSC具有组织再生能力,突出了它们在未来治疗应用中的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/ba2aa2f67da5/BTM2-9-e10629-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/daa282a913bc/BTM2-9-e10629-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/06104014de61/BTM2-9-e10629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/561fa25fa658/BTM2-9-e10629-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/c933c98f22a0/BTM2-9-e10629-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/836c6d274449/BTM2-9-e10629-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/ba2aa2f67da5/BTM2-9-e10629-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/daa282a913bc/BTM2-9-e10629-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/06104014de61/BTM2-9-e10629-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/561fa25fa658/BTM2-9-e10629-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/c933c98f22a0/BTM2-9-e10629-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/836c6d274449/BTM2-9-e10629-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bda6/10905541/ba2aa2f67da5/BTM2-9-e10629-g002.jpg

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