Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice
BackgroundStem 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-Prkdcscid...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1558310/full |
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| author | Lijuan Xia Jinjin Shao Qian Yang Chengda Zhang Zhiqi Xie Linying Wang Cong Xu Siming Zhang Jing Liu Jing Liu Fang 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 Lijiang Zhang |
| author_facet | Lijuan Xia Jinjin Shao Qian Yang Chengda Zhang Zhiqi Xie Linying Wang Cong Xu Siming Zhang Jing Liu Jing Liu Fang 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 Lijiang Zhang |
| author_sort | Lijuan Xia |
| collection | DOAJ |
| description | BackgroundStem 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-PrkdcscidIL2rgtm1Sug/JicCrl (NOG) mice.MethodsMice 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.ResultsNo 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.ConclusionThe 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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| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-e9720f8338274be4bbb97c4493d4eb502025-08-20T02:00:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-03-011310.3389/fcell.2025.15583101558310Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG miceLijuan Xia0Jinjin Shao1Qian Yang2Chengda Zhang3Zhiqi Xie4Linying Wang5Cong Xu6Siming Zhang7Jing Liu8Jing Liu9Fang Liu10Fang Liu11Yuhua Shi12Liqiang Gu13Xiaobo Lin14Jiahong Wang15Ying Chen16Yunxiang Chen17Xin Pan18Feifei Wu19Ruolang Pan20Jinfeng Liang21Lijiang Zhang22Lijiang Zhang23Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaWuyi First People’s Hospital, Affiliated Hospital, School of Medicine, Hangzhou City University, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaQingshan Lake Science and Technology Innovation Center, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaQingshan Lake Science and Technology Innovation Center, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaZhejiang Key Laboratory of Cell-Based Drug and Applied Technology Development, S-Evans Biosciences Co., Ltd., Hangzhou, ChinaZhejiang Key Laboratory of Cell-Based Drug and Applied Technology Development, S-Evans Biosciences Co., Ltd., Hangzhou, ChinaZhejiang Key Laboratory of Cell-Based Drug and Applied Technology Development, S-Evans Biosciences Co., Ltd., Hangzhou, ChinaZhejiang Center for Drugs and Cosmetics Evaluation, Zhejiang Province Food and Drug Administration, Hangzhou, ChinaKey Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou, ChinaQingshan Lake Science and Technology Innovation Center, Hangzhou Medical College, Hangzhou, ChinaBackgroundStem 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-PrkdcscidIL2rgtm1Sug/JicCrl (NOG) mice.MethodsMice 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.ResultsNo 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.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fcell.2025.1558310/fullhuman umbilical cord mesenchymal stem cellssubcutaneous injectiontoxicity assessmentNOG micefoamy cells |
| spellingShingle | Lijuan Xia Jinjin Shao Qian Yang Chengda Zhang Zhiqi Xie Linying Wang Cong Xu Siming Zhang Jing Liu Jing Liu Fang 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 Lijiang Zhang Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice Frontiers in Cell and Developmental Biology human umbilical cord mesenchymal stem cells subcutaneous injection toxicity assessment NOG mice foamy cells |
| title | Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice |
| title_full | Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice |
| title_fullStr | Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice |
| title_full_unstemmed | Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice |
| title_short | Repeat-dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in NOG mice |
| title_sort | repeat dose toxicity of human umbilical cord mesenchymal stem cells via subcutaneous injection in nog mice |
| topic | human umbilical cord mesenchymal stem cells subcutaneous injection toxicity assessment NOG mice foamy cells |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1558310/full |
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