Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets

被引:18
作者
Kim, Jaehyup [1 ,2 ]
Breunig, Melissa J. [1 ]
Escalante, Leah E. [1 ]
Bhatia, Neehar [1 ,2 ]
Denu, Ryan A. [1 ]
Dollar, Bridget A. [1 ]
Stein, Andrew P. [1 ]
Hanson, Summer E. [1 ,3 ]
Naderi, Nadia [1 ,4 ]
Radek, James [5 ]
Haughy, Dermot [5 ]
Bloom, Debra D. [1 ,2 ]
Assadi-Porter, Fariba M. [5 ,6 ]
Hematti, Peiman [1 ,2 ,7 ]
机构
[1] Univ Wisconsin Madison, Sch Med & Publ Hlth, Madison, WI USA
[2] Univ Wisconsin, Dept Med, Madison, WI USA
[3] Univ Wisconsin, Div Plast & Reconstruct Surg, Madison, WI USA
[4] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA
[5] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA
[6] Natl Magnet Resonance Facil, Madison, WI USA
[7] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA
关键词
immunomodulation; mesenchymal stromal cells; pancreatic islets; pancreatic islet transplantation; DIACETATE SUCCINIMIDYL ESTER; STEM-CELLS; BONE-MARROW; IN-VITRO; TISSUE-REPAIR; IMMUNOLOGICAL-PROPERTIES; PRECURSOR CELLS; TRANSPLANTATION; INSULIN; DIFFERENTIATION;
D O I
10.3109/14653249.2012.684376
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:925 / 935
页数:11
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