A Comparative Analysis of the Wound Healing-Related Heterogeneity of Adipose-Derived Stem Cells Donors

Abstract

Adipose-derived Stem cells (ASCs) are on the verge of being available for large clinical trials in wound healing. However, for developing advanced therapy medicinal products (ATMPs), potency assays mimicking the mode of action are required to control the product consistency of the cells. Thus, greater effort should go into the design of product assays. Therefore, we analyzed three ASC-based ATMPs from three different donors with respect to their surface markers, tri-lineage differentiation, proliferation, colony-forming unit capacity, and effect on fibroblast proliferation and migration, endothelial proliferation, migration, and angiogenesis. Furthermore, the transcriptome of all three cell products was analyzed through RNA-sequencing. Even though all products met the criteria by the International Society for Cell and Gene Therapy and the International Federation for Adipose Therapeutics and Science, we found one product to be consistently superior to others when exploring their potency in the wound healing specific assays. Our results indicate that certain regulatory genes associated with extracellular matrix and angiogenesis could be used as markers of a superior ASC donor from which to use ASCs to treat chronic wounds. Having a panel of assays capable of predicting the potency of the product would ensure the patient receives the most potent product for a specific indication, which is paramount for successful patient treatment and acceptance from the healthcare system.

Keywords

• adipose-derived stem cells
• heterogeneity
• transcriptome
• wound healing
• angiogenesis
• extracellular matrix