Quantitative Proteomics Evaluation of Human Multipotent Stromal Cell for β Cell Regeneration

Human multipotent stromal cells (hMSCs) are one of the most versatile cell types used in regenerative medicine due to their ability to respond to injury. In the context of diabetes, it has been previously shown that the regenerative capacity of hMSCs is donor specific after transplantation into streptozotocin (STZ)-treated immunodeficient mice. However, in vivo transplantation models to determine regenerative potency of hMSCs are lengthy, costly, and low throughput. Therefore, a high-throughput quantitative proteomics assay was developed to screen β cell regenerative potency of donor-derived hMSC lines. Using proteomics, we identified 16 proteins within hMSC conditioned media that effectively identify β cell regenerative hMSCs. This protein signature was validated using human islet culture assay, ELISA, and the potency was confirmed by recovery of hyperglycemia in STZ-treated mice. Herein, we demonstrated that quantitative proteomics can determine sample-specific protein signatures that can be used to classify previously uncharacterized hMSC lines for β cell regenerative clinical applications. [Display omitted] •The secretome of hMSCs contains unique signatures useful for potency analyses•Quantitative proteomics and machine learning predict β cell regenerative hMSCs•Secreted levels of IL-6 and CXCL8 are predictive of regenerative potency•Donor characteristics play an important role in the regenerative potency of hMSCs High-throughput quantitative assays that assess regenerative potency of human multipotent stromal cells (hMSCs) need to be established to evaluate their therapeutic potential. Kuljanin et al. develop a quantitative proteomics analyses of secreted proteins combined with in vivo mouse models to determine a protein signature that is predictive for β cell regeneration.