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Biodistribution-based Administration of cGMP-compliant Human Umbilical Cord Mesenchymal Stem Cells Affects the Therapeutic Effect of Wound Healing

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Abstract

Background

Although mesenchymal stem cells (MSCs) are used as therapeutic agents for skin injury therapy, few studies have reported the effects of dosing duration and delivery frequency on wound healing. In addition, before the clinical application of MSCs, it is important to assess whether their usage might influence tumor occurrence.

Methods

We described the metabolic patterns of subcutaneous injection of hUC-MSCs using fluorescence tracing and qPCR methods and applied them to the development of drug delivery strategies for promoting wound healing.

Results

(i) We developed cGMP-compliant hUC-MSC products with critical quality control points for wound healing; (ii) The products did not possess any tumorigenic or tumor-promoting/inhibiting ability in vivo; (iii) Fluorescence tracing and qPCR analyses showed that the subcutaneous application of hUC-MSCs did not result in safety-relevant biodistribution or ectopic migration; (iv) Reinjecting hUC-MSCs after significant consumption significantly improved reepithelialization and dermal regeneration.

Conclusions

Our findings provided a reference for controlling the quality of MSC products used for wound healing and highlighted the importance of delivery time and frequency for designing in vivo therapeutic studies.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

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Funding

This research was funded by Science and Technology SMEs Innovation Capacity Improvement Project of Shandong Province (Grant No. 2022TSGC1004); China National Key R&D Program during the 14th Five-year Plan Period (Grant No. 2021YFA1101500).

Author information

Author notes

  1. Xin Wang and Qiuhong Wang contributed equally to this work.

Authors and Affiliations

  1. Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji’nan, Shandong, 250000, People’s Republic of China

    Xin Wang, Qiuhong Wang, Lingjiao Meng, Ruifeng Tian, Huizhen Guo & Yi Tan

  2. School of Medicine, Northwest University, Xi’an, China

    Zengqi Tan

  3. Shandong Yinfeng Life Science Research Institute, Ji’nan, People’s Republic of China

    Yi Tan

Authors
  1. Xin Wang
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Contributions

Conceptualization, W.X. and T.Y.; methodology, W.QH., W.X., M.LJ.; validation, W.QH. and T.RF.; investigation, W.X.; data curation, W.QH. and G.HZ.; writing—W.X. and T.ZQ.; supervision, T.Y. and W.X.; project administration, W.X. and T.Y. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Yi Tan.

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Ethical Approval

Human umbilical cords were harvested with written informed consent from the donor. All procedures performed involving human participants in experiments were carried out per ethical standards of the institutional and/or national research committee and the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The animal study was carried out in accordance with the commendations of the Institutional Animal Care and Use Committee of Northwest University. The protocol was approved by the Institutional Animal Care and Use Committee of Northwest University.

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The patients/participants provided their written informed consent to participate in this study.

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The authors declare no competing interests.

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Wang, X., Wang, Q., Meng, L. et al. Biodistribution-based Administration of cGMP-compliant Human Umbilical Cord Mesenchymal Stem Cells Affects the Therapeutic Effect of Wound Healing. Stem Cell Rev and Rep 20, 329–346 (2024). https://doi.org/10.1007/s12015-023-10644-9

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