Abstract
Background aims. Mesenchymal stromal cells (MSC) have now been shown to reside in numerous tissues throughout the body, including the pancreas. Ex vivo culture-expanded MSC derived from many tissues display important interactions with different types of immune cells in vitro and potentially play a significant role in tissue homeostasis in vivo. In this study, we investigated the biologic and immunomodulatory properties of human pancreatic islet-derived MSC. Methods. We culture-expanded MSC from cadaveric human pancreatic islets and characterized them using flow cytometry, differentiation assays and nuclear magnetic resonance-based metabolomics. We also investigated the immunologic properties of pancreatic islet-derived MSC compared with bone marrow (BM) MSC. Results. Pancreatic islet and BM-derived MSC expressed the same cell-surface markers by flow cytometry, and both could differentiate into bone, fat and cartilage. Metabolomics analysis of MSC from BM and pancreatic islets also showed a similar set of metabolic markers but quantitative polymerase chain reactions showed that pancreatic islet MSC expressed more interleukin(IL)-1b, IL-6, STAT3 and FGF9 compared with BM MSC, and less IL-10. However, similar to BM MSC, pancreatic islet MSC were able to suppress proliferation of allogeneic T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies. Conclusions. Our in vitro analysis shows pancreatic islet-derived MSC have phenotypic, biologic and immunomodulatory characteristics similar, but not identical, to BM-derived MSC. We propose that pancreatic islet-derived MSC could potentially play an important role in improving the outcome of pancreatic islet transplantation by promoting engraftment and creating a favorable immune environment for long-term survival of islet allografts.
Acknowledgments
We would like to thank the Integrated Islet Distribution Program (IIDP) and University of Wisconsin IIDP Center, especially Dr. Luis Fernandez, for generously providing pancreatic islet samples. We would also like to acknowledge the Experimental Histology Core Facility at the University of Wisconsin Carbone Cancer Center for processing and staining of chondrogenic pellets.
This work was supported by NHLBI-NIH K08 HL081076 grant to PH, NIH R01 DC009018 and RC4EY021357 to FPA, and P41 RR 02301 from the NIH Center for Research Resources.
Author contribution summary: Jaehyup Kim, conception and design, performing experiments, collection of data, data analysis, manuscript writing; Melissa J. Breunig, performing experiments, collection of data; Leah E. Escalante, performing experiments; Neehar Bhatia, performing experiments, collection of data, data analysis; Ryan A. Denu, performing experiments, Bridget A. Dollar, performing experiments; Andrew P. Stein, performing experiments; Summer E. Hanson, performing experiments, collection of data; Nadia Naderi, data analysis; James Radek, NMR data collection; Dermot Haughy, NMR data processing and analysis; Debra D. Bloom, data analysis; Fariba M. Porter-Assadi, NMR data interpretation, manuscript writing; Peiman Hematti, conception and design, provision of study material, data analysis and interpretation, manuscript writing.
Disclosure of potential conflicts of interest: The authors have declared that no potential conflicts of interests exist.