Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice.

IF 4.6 2区生物学 Q2 CELL BIOLOGY

Frontiers in Cell and Developmental Biology Pub Date : 2025-03-03 eCollection Date: 2025-01-01 DOI:10.3389/fcell.2025.1558310

Lijuan Xia, Jinjin Shao, Qian Yang, Chengda Zhang, Zhiqi Xie, Linying Wang, Cong Xu, Siming Zhang, Jing Liu, Fang Liu, Yuhua Shi, Liqiang Gu, Xiaobo Lin, Jiahong Wang, Ying Chen, Yunxiang Chen, Xin Pan, Feifei Wu, Ruolang Pan, Jinfeng Liang, Lijiang Zhang

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引用次数: 0

Abstract

Background: Stem cell therapy shows promise for treating skin diseases and enhancing medical aesthetics. However, safety data for subcutaneous injection of stem cells remain limited. In this study, we evaluated the toxicity of human umbilical cord mesenchymal stem cells (hUC-MSCs) in NOD. Cg-Prkdc^scidIL2rg^tm1Sug/JicCrl (NOG) mice.

Methods: Mice received subcutaneous hUC-MSC injections at doses of 2.5 × 10⁷ and 2.0 × 10⁸ cells/kg on days 1, 8, 12, 16, and 20, followed by withdrawal and observation for 6 weeks. Toxicity was assessed through clinical observation, behavioral analysis, pathology, organ weight measurements, and histopathology. hUC-MSC distribution was determined via validated quantitative (q)PCR and colonization was assessed using immunohistochemistry.

Results: No abnormal effects on clinical responses, body weight, or food intake were observed following five repeated hUC-MSCs administrations, except for masses at the administration site in the high-dose group. Mouse activity levels increased in both dose groups 6 h post-final injection. Foamy cells were observed under the pleural membrane in high-dose mice. hUC-MSCs primarily colonized and were distributed within skin tissues 24 h after the last administration.

Conclusion: The no-observed-adverse-effect level for subcutaneous hUC-MSC administration in NOG mice over 3 weeks was 2.5 × 10⁷ cells/kg. Our results will help in advancing the clinical use of hUC-MSCs, particularly for treating conditions such as atopic dermatitis.

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来源期刊

Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

9.70

自引率

3.60%

发文量

2531

审稿时长

12 weeks

期刊介绍： Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.