title: Age of the donor reduces the ability of human adipose-derived stem cells to alleviate symptoms in the experimental autoimmune encephalomyelitis mouse model.
abstract: There is a significant clinical need for effective therapies for primary progressive multiple sclerosis, which presents later in life (i.e., older than 50 years) and has symptoms that increase in severity without remission. With autologous mesenchymal stem cell therapy now in the early phases of clinical trials for all forms of multiple sclerosis (MS), it is necessary to determine whether autologous stem cells from older donors have therapeutic effectiveness. In this study, the therapeutic efficacy of human adipose-derived mesenchymal stem cells (ASCs) from older donors was directly compared with that of cells from younger donors for disease prevention. Mice were induced with chronic experimental autoimmune encephalomyelitis (EAE) using the myelin oligodendrocyte glycoprotein35-55 peptide and treated before disease onset with ASCs derived from younger (<35 years) or older (>60 years) donors. ASCs from older donors failed to ameliorate the neurodegeneration associated with EAE, and mice treated with older donor cells had increased central nervous system inflammation, demyelination, and splenocyte proliferation in vitro compared with the mice receiving cells from younger donors. Therefore, the results of this study demonstrated that donor age significantly affects the ability of human ASCs to provide neuroprotection, immunomodulation, and/or remyelination in EAE mice. The age-related therapeutic differences corroborate recent findings that biologic aging occurs in stem cells, and the differences are supported by evidence in this study that older ASCs, compared with younger donor cells, secrete less hepatocyte growth factor and other bioactive molecules when stimulated in vitro. These results highlight the need for evaluation of autologous ASCs derived from older patients when used as therapy for MS.
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine and.
authors.forename: Brittni A
authors.initials: BA
authors.lastname: Scruggs
authors.forename: Julie A
authors.initials: JA
authors.lastname: Semon
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Shijia
authors.initials: S
authors.lastname: Zhang
authors.forename: Annie C
authors.initials: AC
authors.lastname: Bowles
authors.forename: Amitabh C
authors.initials: AC
authors.lastname: Pandey
authors.forename: Kathleen M P
authors.initials: KM
authors.lastname: Imhof
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000367:Age Factors; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors
chemical_list: D016207:Cytokines
keywords: Adult stem cells; Aging; Cell transplantation; EAE; Experimental autoimmune encephalomyelitis; Experimental models; Mesenchymal stem cells; Multiple sclerosis
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