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Clin Immunol. 2016 Feb;163:34-41. doi: 10.1016/j.clim.2015.12.002. Epub 2015 Dec 8.

Restoration of t cell substes of patients with type 1 diabetes mellitus by microencapsulated human umbilical cord Wharton jelly-derived mesenchymal stem cells: An in vitro study.

Author information

1
Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: pia.montanucci@unipg.it.
2
Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: alessia.alunno@libero.it.
3
Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: gius.basta@gmail.com.
4
Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: o.bistoni@libero.it.
5
Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: teresa_pescara@virgilio.it.
6
Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: s.cater@alice.it.
7
Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: ilaria.pen@libero.it.
8
Department of Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: vittorio.bini@unipg.it.
9
Department of Medicine, Rheumatology Unit, School of Medicine, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: roberto.gerli@unipg.it.
10
Department of Medicine, Section of Cardiovascular, Endocrine and Metabolic Clinical Physiology, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, University of Perugia, Piazzale Gambuli, Perugia, Italy. Electronic address: riccardo.calafiore@unipg.it.

Abstract

Human umbilical cord Wharton jelly-derived mesenchymal stem cells (hUCMS) might apply to treating chronic autoimmune disorders, as already shown for Sjögren's syndrome, including type 1 diabetes mellitus (T1D). Since naked hUCMS grafts encountered restraints, we enveloped hUCMS, within immunoisolatory microcapsules (CpS-hUCMS), made of our endotoxin-free, clinical grade alginate. We then examined the vitro effects of interferon (IFN)-γ-pretreated CpS-hUCMS on Th17 and Treg of T1D patients (n=15) and healthy controls (n=10). Peripheral blood mononuclear cells (PBMCs) were co-cultured with PBMC/CpS-hUCMS: lymphocyte proliferation was assessed by carboxyfluorescein succinimidyl esther (CFSE) dilution assay, and phenotypic analysis of regulatory and effector Tc was also performed. Cytokine expression was performed by bead array and qPCR on IFN-γ-pretreated hUCMS before PBMCs co-culture. CpS-hUCMS restored a correct Treg/Th17 ratio, relevant to the T1D disease process. In summary, we have preliminarily developed a new biohybrid system, associated with immunoregulatory properties, that is ready for in vivo application.

KEYWORDS:

Adult mesenchymal stem cell; HLAG-5; Immunomodulation; Microencapsulation; Proliferation inhibition; Type 1 diabetes mellitus

PMID:
26680606
DOI:
10.1016/j.clim.2015.12.002
[Indexed for MEDLINE]

Publication type, MeSH terms, Substances

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