Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes.
Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes.
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DOI：
10.4049/jimmunol.0900803
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Abdi R
中科院分区：
文献类型：
--
作者：
Fiorina P;Jurewicz M;Augello A;Vergani A;Dada S;La Rosa S;Selig M;Godwin J;Law K;Placidi C;Smith RN;Capella C;Rodig S;Adra CN;Atkinson M;Sayegh MH;Abdi R
使用间充质干细胞（MSC）在1型糖尿病（T1 D）患者中进行的人类临床试验目前正在进行中，而没有在该疾病的小鼠模型中进行预先验证。为了应对这种空白，我们表征了骨髓来源的鼠MSC在T1 D背景下调节免疫应答的能力，如NOD小鼠所示。与NOD小鼠相比，发现BALB/ c-MSC小鼠表达更高水平的负共刺激分子PD-L1，并促进治疗NOD小鼠向Th 2样反应的转变。此外，从抗性菌株（即，非肥胖抗性小鼠或BALB/c），但不是来自NOD小鼠，当给予前驱糖尿病NOD小鼠时，延迟了糖尿病的发作。BALB/c-MSC运输到NOD小鼠的胰腺淋巴结的数量高于提供自体NOD-MSC的NOD小鼠。BALB/c-MSC的给药暂时导致90%的NOD小鼠的高血糖逆转（p = 0.002）。自体NOD-MSC的转移没有给予这样的治疗益处。我们还注意到NOD-MSC处理的小鼠中的软组织和内脏肿瘤，这在这种情况下是唯一观察到的（即，BALB/c-或非肥胖抵抗小鼠-MSC转移不存在肿瘤）。这一观察结果的重要性仍有待于在人类中探索，因为近交系小鼠如NOD可能更容易形成肿瘤。这些数据提供了重要的临床前数据，支持进一步开发T1 D和其他自身免疫性疾病的同种异体MSC治疗的基础。
Human clinical trials in type 1 diabetes (T1D) patients using mesenchymal stem cells (MSC) are presently underway 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 NOD mice. In comparison to NOD mice, BALB/ c-MSC mice 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., nonobese resistant mice 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-MSC-treated mice, which were uniquely observed in this setting (i.e., no tumors were present with BALB/c- or nonobese resistant mice-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 MSC-based therapies for T1D and, potentially, for other autoimmune disorders.
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影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
影响因子：
4.8
作者：
Koç, ON;Day, J;Krivit, W
通讯作者：
Krivit, W
影响因子：
7.7
作者：
Abdi R;Fiorina P;Adra CN;Atkinson M;Sayegh MH
通讯作者：
Sayegh MH
DOI：
10.1128/cdli.6.3.306-310.1999
发表时间：
1999-05-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Azar, ST;Tamim, H;Almawi, WY
通讯作者：
Almawi, WY
PD-L1的组织表达介导外周T细胞耐受性。
影响因子：
15.3
作者：
Keir, ME;Liang, SC;Guleria, I;Latchman, YE;Qipo, A;Albacker, LA;Koulmanda, M;Freeman, GJ;Sayegh, MH;Sharpe, AH
通讯作者：
Sharpe, AH