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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی I-1: Mesenchymal Stem Cell Therapy
چکیده انگلیسی مقاله Human clinical trials in type 1 diabetes (T1D) patients are presently underway using mesenchymal stem cells (MSCs) without prior validation in a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC for their ability to modulate immune responses in the context of T1D, as represented in non-obese diabetic (NOD) mice. In comparison to NOD-, BALB/c-MSC were found to express higher levels of the negative costimulatory molecule PD-L1 and to promote a shift toward Th2-like responses in treated NOD mice. In addition, transfer of MSC from resistant strains (i.e. NOR or BALB/c), but not from NOD mice, delayed the onset of diabetes when administered to prediabetic NOD mice. The number of BALB/c-MSC trafficking to the pancreatic lymph nodes of NOD mice was higher than in NOD mice provided autologous NOD-MSC. Administration of BALB/c- MSC temporarily resulted in reversal of hyperglycemia in 90% of NOD mice (p=0.002). Transfer of autologous NOD-MSC imparted no such therapeutic benefit. We also noted soft tissue and visceral tumors in NOD-MSCtreated mice, which were uniquely observed in this setting (i.e. no tumors were present with BALB/c- or NOR-MSC transfer). The importance of this observation remains to be explored in humans, as inbred mice such as NOD may be more susceptible to tumor formation. These data provide important preclinical data supporting the basis for further development of allogeneic MSCbased therapies for T1D and potentially, for other autoimmune disorders.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1484
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