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

Miljan Kuljanin; Ruth M Elgamal; Gillian I Bell; Dimetri Xenocostas; Anargyros Xenocostas; David A Hess; Gilles A Lajoie

doi:10.1016/j.celrep.2018.10.107

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

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

Authors

Miljan Kuljanin¹, Ruth M Elgamal², Gillian I Bell³, Dimetri Xenocostas³, Anargyros Xenocostas⁴, David A Hess⁵, Gilles A Lajoie⁶

Affiliations

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.

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

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Animals
Body Mass Index
Cell Line
Culture Media, Conditioned / pharmacology
Female
Humans
Insulin-Secreting Cells / drug effects
Insulin-Secreting Cells / metabolism*
Male
Mice, Inbred NOD
Mice, SCID
Middle Aged
Multipotent Stem Cells / drug effects
Multipotent Stem Cells / metabolism*
Proteomics / methods*
Regeneration*
Reproducibility of Results
Stromal Cells / drug effects
Stromal Cells / metabolism
Support Vector Machine
Tissue Donors
Young Adult

Substances

Culture Media, Conditioned