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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1558310
Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice
Provisionally accepted
Lijuan Xia 1*
Jinjin Shao 1 Qian Yang 1*
Zhang Chengda 1
Zhiqi Xie 2 Linying Wang 1*
Cong Xu 1 Siming Zhang 1*
Liu Jing 1 Fang Liu 1* Yuhua Shi 1* Liqiang Gu 1* Xiaobo Lin 1* Jiahong Wang 1* Ying Chen 1* Yunxiang Chen 1* Xin Pan 3* Feifei Wu 3*
Ruolang Pan 3 Jinfeng Liang 4* Lijiang Zhang 1*- 1 Hangzhou Medical College, hangzhou, China
- 2 Hangzhou City University, Hangzhou, China
- 3 S-Evans Biosciences, hangzhou, China
- 4 ZheJiang Institute For Food and Drug Control, Hangzhou, Zhejiang Province, China
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 scid IL2rg tm1Sug /JicCrl (NOG) mice.Methods: Mice received subcutaneous hUC-MSC injections at doses of 2.5 × 10 7 and 2.0 × 10 8 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.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.The no-observed-adverse-effect level for subcutaneous hUC-MSC administration in NOG mice over 3 weeks was 2.5 × 10 7 cells/kg. Our results will help in advancing the clinical use of hUC-MSCs, particularly for treating conditions such as atopic dermatitis.
Keywords: Human umbilical cord mesenchymal stem cells, Subcutaneous injection, Toxicity assessment, NOG mice, Foamy cells
Received: 10 Jan 2025; Accepted: 10 Feb 2025.
Copyright: © 2025 Xia, Shao, Yang, Chengda, Xie, Wang, Xu, Zhang, Jing, Liu, Shi, Gu, Lin, Wang, Chen, Chen, Pan, Wu, Pan, Liang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lijuan Xia, Hangzhou Medical College, hangzhou, China
Qian Yang, Hangzhou Medical College, hangzhou, China
Linying Wang, Hangzhou Medical College, hangzhou, China
Siming Zhang, Hangzhou Medical College, hangzhou, China
Fang Liu, Hangzhou Medical College, hangzhou, China
Yuhua Shi, Hangzhou Medical College, hangzhou, China
Liqiang Gu, Hangzhou Medical College, hangzhou, China
Xiaobo Lin, Hangzhou Medical College, hangzhou, China
Jiahong Wang, Hangzhou Medical College, hangzhou, China
Ying Chen, Hangzhou Medical College, hangzhou, China
Yunxiang Chen, Hangzhou Medical College, hangzhou, China
Xin Pan, S-Evans Biosciences, hangzhou, China
Feifei Wu, S-Evans Biosciences, hangzhou, China
Jinfeng Liang, ZheJiang Institute For Food and Drug Control, Hangzhou, Zhejiang Province, China
Lijiang Zhang, Hangzhou Medical College, hangzhou, China
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