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Cell Rep. 2018 Nov 27;25(9):2524-2536.e4. doi: 10.1016/j.celrep.2018.10.107.

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

Author information

1
Don Rix Protein Identification Facility, Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Krembil Centre for Stem Cell Biology, Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada.
2
Krembil Centre for Stem Cell Biology, Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
3
Krembil Centre for Stem Cell Biology, Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada.
4
Department of Medicine, Division of Hematology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
5
Krembil Centre for Stem Cell Biology, Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. Electronic address: dhess@robarts.ca.
6
Don Rix Protein Identification Facility, Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. Electronic address: glajoie@uwo.ca.

Abstract

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.

KEYWORDS:

NOD/SCID; diabetes; human multipotent stromal cells; islet regeneration; label free quantitation; mass spectrometry; proteomics; secretome; targeted proteomics; β cell regeneration

PMID:
30485817
DOI:
10.1016/j.celrep.2018.10.107
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