title: Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro.
abstract: : 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.
  
  
  CONCLUSIONS
  The potential for mesenchymal stromal cells (MSCs) as a cell-based therapy in the treatment of immunologic disorders has been well established. Recent studies reported the clinical potential for autologous MSCs as a systemic therapy in the treatment of type I diabetes mellitus (T1D). The current study compared the genotypic and phenotypic profiles of bone marrow-derived MSCs from T1D and healthy donors as autologous (compared with allogeneic) therapy provides distinct advantages, such as reduced risk of immune reaction and transmission of infectious agents. The findings of the current study demonstrate that despite moderate differences in T1D MSCs at the gene level, these cells can be expanded in culture to an extent corresponding to that of MSCs derived from healthy donors. No functional difference in terms of immunosuppressive activity, blood compatibility, or migratory capacity was evident between the groups. The study findings also show that autologous MSC therapy holds promise as a T1D treatment and should be evaluated further in clinical trials.
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Divisions of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: Davies
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Divisions of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Alm
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Divisions of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Heldring
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Divisions of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Moll
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.|Divisions of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gavin
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Batsis
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.affiliation: Institution for Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
authors.affiliation: Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.affiliation: Division of Transplantation, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Lauri E
authors.initials: LE
authors.lastname: Kyllonen
authors.affiliation: Division of Transplantation, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Kaija T
authors.initials: KT
authors.lastname: Salmela
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Sweden.|Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Carlsson
authors.affiliation: Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.affiliation: Center for Hematology and Regenerative Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden katarina.leblanc@ki.se.|Divisions of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
keywords: Adult human bone marrow; Cellular therapy; Diabetes; Immunosuppression; Mesenchymal stem cells