title: Differential efficacy of human mesenchymal stem cells based on source of origin.
abstract: Mesenchymal stem cells (MSCs) are useful in tissue repair but also possess immunomodulatory properties. Murine and uncontrolled human trials suggest efficacy of MSCs in treating lupus. Autologous cells are preferable; however, recent studies suggest that lupus-derived MSCs lack efficacy in treating disease. Thus, the optimum derivation of MSCs for use in lupus is unknown. It is also unknown which in vitro assays of MSC function predict in vivo efficacy. The objectives for this study were to provide insight into the optimum source of MSCs and to identify in vitro assays that predict in vivo efficacy. We derived MSCs from four umbilical cords, four healthy bone marrows (BMs), and four lupus BMs. In diseased MRL/lpr mice, MSCs from healthy BM and umbilical cords significantly decreased renal disease, whereas lupus BM MSCs only delayed disease. Current in vitro assays did not differentiate efficacy of the different MSCs. However, differences in MSC efficacy were observed in B cell proliferation assays. Our results suggest that autologous MSCs from lupus patients are not effective in treating disease. Furthermore, standard in vitro assays for MSC licensing are not predictive of in vivo efficacy, whereas inhibiting B cell proliferation appears to differentiate effective MSCs from ineffective MSCs.
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; collinel@musc.edu.
authors.forename: Erin
authors.initials: E
authors.lastname: Collins
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China;
authors.forename: Fei
authors.initials: F
authors.lastname: Gu
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425;
authors.forename: Maosong
authors.initials: M
authors.lastname: Qi
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425;
authors.forename: Ivan
authors.initials: I
authors.lastname: Molano
authors.affiliation: Department of Pathology, University of Miami School of Medicine, Miami, FL 33136; and.
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.affiliation: Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China;
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.affiliation: Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425; Medical Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29403.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
mesh_terms: D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators