Cargando…

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 ord...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Xiujuan, Bowles, Annie C., Semon, Julie A., Scruggs, Brittni A., Zhang, Shijia, Strong, Amy L., Gimble, Jeffrey M., Bunnell, Bruce A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897387/
https://www.ncbi.nlm.nih.gov/pubmed/24465465
http://dx.doi.org/10.1371/journal.pone.0085007
_version_ 1782300223676088320
author Zhang, Xiujuan
Bowles, Annie C.
Semon, Julie A.
Scruggs, Brittni A.
Zhang, Shijia
Strong, Amy L.
Gimble, Jeffrey M.
Bunnell, Bruce A.
author_facet Zhang, Xiujuan
Bowles, Annie C.
Semon, Julie A.
Scruggs, Brittni A.
Zhang, Shijia
Strong, Amy L.
Gimble, Jeffrey M.
Bunnell, Bruce A.
author_sort Zhang, Xiujuan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3897387
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38973872014-01-24 Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model Zhang, Xiujuan Bowles, Annie C. Semon, Julie A. Scruggs, Brittni A. Zhang, Shijia Strong, Amy L. Gimble, Jeffrey M. Bunnell, Bruce A. PLoS One Research Article 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. Public Library of Science 2014-01-21 /pmc/articles/PMC3897387/ /pubmed/24465465 http://dx.doi.org/10.1371/journal.pone.0085007 Text en © 2014 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Xiujuan
Bowles, Annie C.
Semon, Julie A.
Scruggs, Brittni A.
Zhang, Shijia
Strong, Amy L.
Gimble, Jeffrey M.
Bunnell, Bruce A.
Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model
title Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model
title_full Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model
title_fullStr Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model
title_full_unstemmed Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model
title_short Transplantation of Autologous Adipose Stem Cells Lacks Therapeutic Efficacy in the Experimental Autoimmune Encephalomyelitis Model
title_sort transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897387/
https://www.ncbi.nlm.nih.gov/pubmed/24465465
http://dx.doi.org/10.1371/journal.pone.0085007
work_keys_str_mv AT zhangxiujuan transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT bowlesanniec transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT semonjuliea transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT scruggsbrittnia transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT zhangshijia transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT strongamyl transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT gimblejeffreym transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel
AT bunnellbrucea transplantationofautologousadiposestemcellslackstherapeuticefficacyintheexperimentalautoimmuneencephalomyelitismodel