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

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2023-11-29 DOI:10.1002/btm2.10629
Jiseong Kim, Jin-Su Kim, Dohyun Kim, Alvin Bacero Bello, Byoung Ju Kim, Byung-Hyun Cha, Soo-Hong Lee
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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.

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人间充质干细胞衍生畸胎瘤对骨软骨缺损再生的治疗潜力
人类诱导多能干细胞(iPSCs)可以分化为特定的细胞类型,特别是间充质干细胞(MSCs),因此在个性化医疗方面具有很大的前景。因此,我们的研究试图评估从人多能干细胞产生的畸胎瘤中提取间充质干细胞的可行性。畸胎瘤作为模拟人类多谱系发育的模型,从而丰富了特定的体细胞祖细胞和干细胞。在这里,我们在ipsc产生的畸胎瘤中发现了一个小的,凝聚的MSCs团块。之后,我们成功地从这个凝结的肿块中分离出间充质干细胞,这是畸胎瘤发展的副产品。为了评估ipsc衍生的MSCs (iPSC-MSCs)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分析进行了全面的评估。值得注意的是,iPSC-MSCs表现出与传统MSCs相似的免疫表型,并且它们表现出强大的增殖能力,类似于那些高级多能干细胞衍生的MSCs。此外,iPSC-MSCs在体外表现出分化成多个谱系的能力。最后,我们利用骨软骨缺损模型评估了iPSC-MSCs的治疗潜力。我们的研究结果表明,畸胎瘤是浓缩间充质干细胞分离的一个有希望的来源。更重要的是,我们的研究结果表明,来自畸胎瘤的iPSC-MSCs具有组织再生的能力,这突出了它们在未来治疗应用中的前景。
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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