Abstract
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are present in human umbilical connective tissue and can differentiate into various cell types. Our previous studies have proved that hUC-MSCs do not lead to allergies and tumorigenesis. In the present study, the acute and long-term toxicity of hUC-MSCs in mice and rats was evaluated. The acute toxicity of hUC-MSCs was assessed in 8-week-old mice receiving two caudal intravenous (i.v.) injections of hUC-MSCs at the maximum tolerated dose of 1.5 × 107 cells/kg with an interval of 8 h and the observation period sustained for 14 days. For the long-term toxicity evaluation, rats were randomly divided into control, low-dose (3.0 × 105 cells/kg), mid-dose (1.5 × 106 cells/kg), and high-dose (7.5 × 106 cells/kg) groups, which were treated with hUC-MSCs via a caudal i.v. injection every 3 days for 90 days. Weight and food intake evaluation was performed for all rats for 2 weeks after the hUC-MSC administration. The animals were then sacrificed for hematological, blood biochemical, and pathological analyses, as well as organ index determination. We observed no obvious acute toxicity of hUC-MSCs in mice at the maximum tolerated dose. Long-term toxicity tests in rats showed no significant differences between HUC-MSC-treated and control groups in the following parameters: body weight, hematological and blood biochemical parameters, and histopathologic changes in the heart, liver, kidneys, and lungs. This study provides evidence of the safety of i.v. hUC-MSCs infusion for future clinical therapies.
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The data that support the findings of this study are available from the corresponding author upon reasonable request. The datasets generated during or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by the study supported by National natural science foundation of China [NO. 81860089] ; Doctoral Foundation of Guizhou Medical University[2020]018, The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT31048] ; Science and Technology Foundation Project of Guizhou Health Committee [gzwjkj2019-1-099].
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JX: Conceptualization,Methodology,Software,Investigation,Writing- Original Draft. GL: Methodology, Investigation, Writing—Original Draft. XW: Validation, Formal analysis, Visualization, Software. YH: Validation, Formal analysis, Visualization. HL: Conceptualization, Methodology. LY: Software, Investigation. ZF: Methodology, Software, Investigation. CL: Validation, Formal analysis, Visualization. MK: Visualization, Software. LZ: Methodology, Software, Investigation. YZ: Writing—Review & Editing, Supervision, Data Curation. XQ: Resources, Writing—Review & Editing, Supervision, Data Curation.
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Xu, J., Liu, G., Wang, X. et al. hUC-MSCs: evaluation of acute and long-term routine toxicity testing in mice and rats. Cytotechnology 74, 17–29 (2022). https://doi.org/10.1007/s10616-021-00502-2
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DOI: https://doi.org/10.1007/s10616-021-00502-2