Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy.
Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy.
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与单一疗法相比，Treg和间充质基质细胞的组合疗法增强创伤性脑损伤后炎症的效力和减弱。
DOI：
10.1002/stem.3320
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Cox CS Jr
中科院分区：
文献类型：
--
作者：
Caplan HW;Prabhakara KS;Toledano Furman NE;Zorofchian S;Kumar A;Martin C;Xue H;Olson SD;Cox CS Jr
创伤性脑损伤（TBI）后的炎症反应可导致严重的继发性脑损伤和中枢神经系统（CNS）内的慢性炎症。包括间充质基质细胞 (MSC) 在内的细胞疗法已经改善了 TBI 动物模型，并且正在人体试验中进行研究。 MSC 治疗潜力的一种潜在机制是其增强免疫抑制性调节 T 细胞 (Treg) 内源性反应的能力。我们最近发现，在啮齿类动物模型中，输注人脐带血 Treg 可减少 TBI 后的慢性小胶质细胞增生，并改变全身免疫反应。这些细胞可能使用重叠和不同的机制来调节免疫系统。因此，将 Treg 和 MSC 结合作为联合疗法可能比任一单一疗法具有治疗益处。然而，Treg+MSC联合治疗TBI的研究还缺乏。在本研究中，我们比较了 MSC+Treg 联合疗法以及 MSC 和 Treg 单一疗法在体内和体外抑制 TBI 神经炎症反应的能力。与单一疗法相比，Treg+MSC 联合疗法在减少神经和外周炎症反应方面具有更强的功效；此外，输注时机被证明是 MSC 单一疗法和 Treg+MSC 联合疗法体内和体外疗效的显着变量。
The inflammatory response after traumatic brain injury (TBI) can lead to significant secondary brain injury and chronic inflammation within the central nervous system (CNS). Cell therapies, including mesenchymal stromal cells (MSC), have led to improvements in animal models of TBI and are under investigation in human trials. One potential mechanism for the therapeutic potential of MSC is their ability to augment the endogenous response of immune suppressive regulatory T cells (Treg). We have recently shown that infusion of human cord blood Treg decreased chronic microgliosis after TBI and altered the systemic immune response in a rodent model. These cells likely use both overlapping and distinct mechanisms to modulate the immune system; therefore, combining Treg and MSC as a combination therapy may confer therapeutic benefit over either monotherapy. However, investigation of Treg+MSC combination therapy in TBI is lacking. In this study, we compared the ability MSC+Treg combination therapy, as well as MSC and Treg monotherapies, to inhibit the neuroinflammatory response to TBI in vivo and in vitro. Treg+MSC combination therapy demonstrated increased potency to reduce the neuro- and peripheral inflammatory response compared to monotherapy; furthermore, the timing of infusion proved to be a significant variable in the efficacy of both MSC monotherapy and Treg+MSC combination therapy in vivo and in vitro.
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DOI：
10.1016/j.jss.2017.02.078
发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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