Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.
Multiple sclerosis (MS), characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs) for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE), a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.
School of Petroleum & Chemical Engineering, Dalian University of Technology Panjin Campus, Panjin, Liaoning Province, China ; Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
Xiujuan
X
Zhang
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America ; Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, Louisiana, United States of America.
Annie C
AC
Bowles
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
Julie A
JA
Semon
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America ; Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
Brittni A
BA
Scruggs
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America ; Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
Shijia
S
Zhang
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
Amy L
AL
Strong
Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America.
Jeffrey M
JM
Gimble
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, United States of America ; Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, Louisiana, United States of America ; Division of Regenerative Medicine, Tulane National Primate Research Center, Covington, Louisiana, United States of America.
Bruce A
BA
Bunnell
D017667:Adipocytes / Q000166:cytology / Q000276:immunology; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D014182:Transplantation, Autologous; D017211:Treatment Failure
D015415:Biomarkers; D016207:Cytokines