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Type 1 Diabetes Mellitus Donor Mesenchymal. Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro
Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Clin Immunol, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Transfus Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Clin Immunol, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Transfus Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Clin Immunol, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Transfus Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Clin Immunol, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Div Transfus Med, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
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2016 (English)In: Stem Cells Translational Medicine, ISSN 2157-6564, E-ISSN 2157-6580, Vol. 5, no 11, 1485-1495 p.Article in journal (Refereed) Published
Abstract [en]

Bone marrow mesenchymal stromal cells (BM-MSCs) have been characterized and used in many clinical studies based on their immunomodulatory and regenerative properties. We have recently reported the benefit of autologous MSC systemic therapy in the treatment of type 1 diabetes mellitus (T1D). Compared with allogeneic cells, use of autologous products reduces the risk of eliciting undesired complications in the recipient, including rejection, immunization, and transmission of viruses and prions; however, comparable potency of autologous cells is required for this treatment approach to remain feasible. To date, no analysis has been reported that phenotypically and functionally characterizes MSCs derived from newly diagnosed and late-stage T1D donors in vitro with respect to their suitability for systemic immunotherapy. In this study, we used gene array in combination with functional in vitro assays to address these questions. MSCs from T1D donors and healthy controls were expanded from BM aspirates. BM mononuclear cell counts and growth kinetics were comparable between the groups, with equivalent colony-forming unit-fibroblast capacity. Gene microarrays demonstrated differential gene expression between healthy and late-stage T1D donors in relation to cytokine secretion, immunomodulatory activity, and wound healing potential. Despite transcriptional differences, T1D MSCs did not demonstrate a significant difference from healthy controls in immunosuppressive activity, migratory capacity, or hemocompatibility. We conclude that despite differential gene expression, expanded MSCs from T1D donors are phenotypically and functionally similar to healthy control MSCs with regard to their immunomodulatory and migratory potential, indicating their suitability for use in autologous systemic therapy.

Place, publisher, year, edition, pages
2016. Vol. 5, no 11, 1485-1495 p.
Keyword [en]
Mesenchymal stem cells, Diabetes, Cellular therapy, Immunosuppression, Adult human bone marrow
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-308913DOI: 10.5966/sctm.2015-0272ISI: 000386413800010PubMedID: 27412884OAI: oai:DiVA.org:uu-308913DiVA: diva2:1051202
Funder
Swedish Cancer SocietySwedish Childhood Cancer FoundationSwedish Society for Medical Research (SSMF)Swedish Society of MedicineThe Karolinska Institutet's Research FoundationSwedish Child Diabetes FoundationAFA InsuranceSwedish Diabetes AssociationNovo Nordisk
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Available from: 2016-12-01 Created: 2016-12-01 Last updated: 2016-12-01Bibliographically approved

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Nilsson, BoCarlsson, Per-OlaKorsgren, Olle
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Clinical ImmunologyDepartment of Medical Cell BiologyDepartment of Medical Sciences
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