Costimulation-adhesion blockade is superior to cyclosporine A and prednisone immunosuppressive therapy for preventing rejection of differentiated human embryonic stem cells following transplantation.
Costimulation-adhesion blockade is superior to cyclosporine A and prednisone immunosuppressive therapy for preventing rejection of differentiated human embryonic stem cells following transplantation.
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DOI：
10.1002/stem.1501
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发表时间：
2013-11
期刊：
影响因子：
5.2
通讯作者：
Wu, Joseph C.
中科院分区：
文献类型：
--
作者：
Huber, Bruno C.;Ransohoff, Julia D.;Ransohoff, Katherine J.;Riegler, Johannes;Ebert, Antje;Kodo, Kazuki;Gong, Yongquan;Sanchez-Freire, Veronica;Dey, Devaveena;Kooreman, Nigel G.;Diecke, Sebastian;Zhang, Wendy Y.;Odegaard, Justin;Hu, Shijun;Gold, Joseph D.;Robbins, Robert C.;Wu, Joseph C.
关键词：
人胚胎干细胞（hESC）衍生物是用于治疗用途的有吸引力的候选物。hESC衍生物作为异种移植物或同种异体移植物的植入和存活需要有效的免疫抑制以防止免疫细胞浸润和移植物破坏。为了验证以下假设：与目前的免疫抑制剂相比，两种共刺激-粘附阻断剂的短程双药方案可以诱导更好的hESC衍生物植入。我们用表达萤火虫荧光素酶（Fluc）和增强型绿色荧光蛋白（eGFP）的双融合报告基因构建体转导hESC，并将这些细胞分化为内皮细胞（hESC-EC）。报告基因表达使得能够通过生物发光成像（BLI）纵向评估细胞植入。在后肢模型中，与环孢霉素治疗相比，共刺激-粘附治疗导致上级hESC-EC和小鼠EC植入。在缺血性心肌损伤模型中，共刺激-粘附疗法也促进了hESC-EC和hESC-CM的存活。通过磁共振成像（MRI）评估，改良的hESC-EC植入在心肌损伤后具有心脏保护作用。从机制上讲，共刺激-粘附疗法与T细胞免疫球蛋白和粘蛋白结构域3（TIM 3）的全身性和移植物内上调以及促炎细胞因子谱降低相关。共刺激-粘附疗法是目前临床免疫抑制策略的一种上级替代方案，用于预防hESC衍生物的移植后排斥反应。通过延长细胞植入的窗口，共刺激-粘附疗法增强了缺血性损伤后的功能保护。该方案可能通过TIM 3依赖性机制起作用。
Human embryonic stem cell (hESC) derivatives are attractive candidates for therapeutic use. The engraftment and survival of hESC derivatives as xenografts or allografts require effective immunosuppression to prevent immune cell infiltration and graft destruction. To test the hypothesis that a short-course, dual-agent regimen of two costimulation-adhesion blockade agents can induce better engraftment of hESC derivatives compared to current immunosuppressive agents. We transduced hESCs with a double fusion reporter gene construct expressing firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), and differentiated these cells to endothelial cells (hESC-ECs). Reporter gene expression enabled longitudinal assessment of cell engraftment by bioluminescence imaging (BLI). Costimulation-adhesion therapy resulted in superior hESC-EC and mouse EC engraftment compared to cyclosporine therapy in a hindlimb model. Costimulation-adhesion therapy also promoted robust hESC-EC and hESC-derived cardiomyocyte (hESC-CM) survival in an ischemic myocardial injury model. Improved hESC-EC engraftment had a cardioprotective effect after myocardial injury, as assessed by magnetic resonance imaging (MRI). Mechanistically, costimulation-adhesion therapy is associated with systemic and intra-graft upregulation of T cell immunoglobulin and mucin domain 3 (TIM3) and a reduced pro-inflammatory cytokine profile. Costimulation-adhesion therapy is a superior alternative to current clinical immunosuppressive strategies for preventing the post-transplant rejection of hESC derivatives. By extending the window for cellular engraftment, costimulation-adhesion therapy enhances functional preservation following ischemic injury. This regimen may function through a TIM3-dependent mechanism.
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影响因子：
23.9
作者：
Burridge, Paul W.;Keller, Gordon;Gold, Joseph D.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
5.2
作者：
Hu, Shijun;Wilson, Kitchener D.;Ghosh, Zhumur;Han, Leng;Wang, Yongming;Lan, Feng;Ransohoff, Katherine J.;Burridge, Paul;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
DOI：
10.4049/jimmunol.1001176
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ferrer IR;Wagener ME;Robertson JM;Turner AP;Araki K;Ahmed R;Kirk AD;Larsen CP;Ford ML
通讯作者：
Ford ML
影响因子：
8.7
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
通讯作者：
DeKruyff RH
影响因子：
20.1
作者：
Gu M;Nguyen PK;Lee AS;Xu D;Hu S;Plews JR;Han L;Huber BC;Lee WH;Gong Y;de Almeida PE;Lyons J;Ikeno F;Pacharinsak C;Connolly AJ;Gambhir SS;Robbins RC;Longaker MT;Wu JC
通讯作者：
Wu JC