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

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. 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. (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. 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.