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从其分化的细胞治疗产品中消除致瘤性多能干细胞：迈向确保细胞治疗安全的重要一步。

Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.

作者信息

Movahed Afsaneh Yazdani, Bagheri Rana, Savatier Pierre, Šarić Tomo, Moradi Sharif

机构信息

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

University Lyon, University Lyon 1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, France.

出版信息

Stem Cell Reports. 2025 Jul 8;20(7):102543. doi: 10.1016/j.stemcr.2025.102543. Epub 2025 Jun 19.

DOI:10.1016/j.stemcr.2025.102543
PMID:40541178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12277835/
Abstract

Human pluripotent stem cells (hPSCs) are considered a promising tool for regenerative medicine due to their unique self-renewal and multi-lineage differentiation capabilities. Although over 100 clinical trials have employed hPSC-derived products to treat life-threatening diseases, the tumorigenic risk posed by residual undifferentiated hPSCs remains a formidable obstacle to their clinical implementation. In this review, we summarize current strategies to eliminate tumorigenic hPSCs, most of which target hPSC-specific markers, and critically evaluate the advantages and limitations of each approach. Finally, we discuss various methods that can be used to evaluate the efficiency of pluripotent stem cell (PSC) elimination.

摘要

人类多能干细胞（hPSCs）因其独特的自我更新和多谱系分化能力，被视为再生医学中一种很有前景的工具。尽管已有100多项临床试验使用hPSC衍生产品来治疗危及生命的疾病，但残留未分化hPSCs带来的致瘤风险仍然是其临床应用的巨大障碍。在本综述中，我们总结了当前消除致瘤性hPSCs的策略，其中大多数针对hPSC特异性标志物，并批判性地评估了每种方法的优缺点。最后，我们讨论了可用于评估多能干细胞（PSC）消除效率的各种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/99507cae3e39/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/b34ac7639b4b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/ea02016e3729/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/3da79a25b464/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/b6866adb22ab/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/99507cae3e39/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/b34ac7639b4b/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/ea02016e3729/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/3da79a25b464/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/b6866adb22ab/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ba8/12277835/99507cae3e39/gr4.jpg

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Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review.

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本文引用的文献

[1]
A tumorigenicity evaluation platform for cell therapies based on brain organoids.

Transl Neurodegener. 2024-10-29

[2]
Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient.

Cell. 2024-10-31

[3]
Detection of residual pluripotent stem cells in cell therapy products utilizing droplet digital PCR: an international multisite evaluation study.

Stem Cells Transl Med. 2024-10-10

[4]
Considerations for the development of iPSC-derived cell therapies: a review of key challenges by the JSRM-ISCT iPSC Committee.

Cytotherapy. 2024-11

[5]
Clinical translation of pluripotent stem cell-based therapies: successes and challenges.

Development. 2024-4-1

[6]
Protocol improvement and multisite validation of a digital soft agar colony formation assay for tumorigenic transformed cells intermingled in cell therapy products.

Cytotherapy. 2024-7

[7]
Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD.

Cell Stem Cell. 2023-10-5

[8]
Estimating residual undifferentiated cells in human chemically induced pluripotent stem cell derived islets using lncRNA as biomarkers.

Sci Rep. 2023-9-30

[9]
Time-resolved Small-RNA Sequencing Identifies MicroRNAs Critical for Formation of Embryonic Stem Cells from the Inner Cell Mass of Mouse Embryos.

Stem Cell Rev Rep. 2023-10

[10]
An Ethanol Extract of Induces Apoptotic Cell Death in Induced Pluripotent Stem Cells and Suppresses Teratoma Formation.

Nutrients. 2023-5-18

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