Article

Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice

Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Experimental Neurology (Impact Factor: 4.62). 10/2005; 195(1):16-26. DOI: 10.1016/j.expneurol.2005.03.018
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ABSTRACT We investigated the treatment of remitting-relapsing experimental autoimmune encephalomyelitis (EAE) in mice with human bone marrow stromal cells (hBMSCs). hBMSCs were injected intravenously into EAE mice upon onset of paresis. Neurological functional tests were scored daily by grading clinical signs (score 0-5). Immunohistochemistry was performed to measure the transplanted hBMSCs, cell proliferation (bromodeoxyuridine, BrdU), oligodendrocyte progenitor cells (NG2), oligodendrocytes (RIP), and brain-derived neurotrophic factor (BDNF). The maximum clinical score and the average clinical scores were significantly decreased in the hBMSC-transplanted mice compared to the phosphate-buffered-saline-treated EAE controls, indicating a significant improvement in function. Demyelination significantly decreased, and BrdU(+) and BDNF(+) cells significantly increased in the hBMSC-treated mice compared to controls. Some BrdU(+) cells were colocalized with NG2(+) and RIP(+) immunostaining. hBMSCs also significantly reduced the numbers of vessels containing inflammatory cell infiltration. These data indicate that hBMSC treatment improved functional recovery after EAE in mice, possibly, via reducing inflammatory infiltrates and demyelination areas, stimulating oligodendrogenesis, and by elevating BDNF expression.

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    • "In contrast, mesenchymal stem cells (MSCs) isolated from many adult tissues have recently emerged as potent immunomodulatory cells with therapeutic applications in regenerative medicine (Phinney and Prockop, 2007) and in the treatment of inflammatory and autoimmune disorders (Uccelli and Prockop, 2010). Thus, MSCs derived from bone marrow and adipose tissue were shown to ameliorate experimental autoimmune encephalomyelitis and protected neurons from neuroinflammation in experimental models of brain ischemia and brain injury (Constantin et al., 2009; Uccelli et al., 2011; Zappia et al., 2005; Zhang et al. 2005). Among their multimodal actions, MSCs seem to modulate microglia activation (Kim et al., 2009; Zhou et al., 2009) although the mechanisms involved are largely unknown. "
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    • "The muted in vivo efficacy of BM - MSCs that we observed is consistent with previous reports that showed only mild ( Gordon et al . , 2008 ; Zhang et al . , 2005 ) or negligible ( Payne et al . , 2013 ) effects in the EAE mouse model . Inter - estingly , BM - MSC#6 , the BM - MSC line that caused a modest reduction in EAE disease scores in the preonset model at passage 2 ( Figure 3C ) , failed to show any thera - peutic effects when used at passage 4 during the anti - iL - 6 antibody experiment "
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    • "Mesenchymal stem cells also promote the appearance of regulatory T cells, inducing antigen-specific tolerance. Mesenchymal stem cell immunomodulatory potential has been recognized as the mechanism underlying the therapeutic effect observed in autoimmune diseases such as graft-versus-host disease, experimental encephalomyelitis and diabetes (Le Blanc et al. 2004; Zhang et al. 2005; Ezquer et al. 2012). In these pathological conditions, systemic administration of MSCs prevents the destruction of old and newly generated tissue cells. "
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