Designing biomaterials for the modulation of allogeneic and autoimmune responses to cellular implants in Type 1 Diabetes.
Designing biomaterials for the modulation of allogeneic and autoimmune responses to cellular implants in Type 1 Diabetes.
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DOI：
10.1016/j.actbio.2021.05.039
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发表时间：
2021-10-01
影响因子：
9.7
通讯作者：
Stabler, Cherie L.
中科院分区：
文献类型：
--
作者：
Samojlik, Magdalena M.;Stabler, Cherie L.
适应性免疫应答的有效抑制对于同种异体细胞疗法的成功至关重要。在1型糖尿病的胰岛移植中，预先存在的自身免疫提供了额外的障碍，因为记忆性自身免疫T细胞介导对供体β细胞的自身抗原特异性攻击和对供体移植细胞的同种异体抗原特异性攻击。用于胰岛移植的免疫抑制剂通常在抑制同种免疫应答方面是成功的，但显著地阻碍了这种治疗方法的广泛采用，并且未能控制记忆T细胞群，这使得移植物容易受到破坏。在这篇综述中，我们强调了生物材料的能力，以提供本地和细微的指示，以抑制或改变免疫途径激活同种异体胰岛移植。生物材料免疫隔离是用于阻断直接抗原识别和下游细胞介导的移植物破坏的常用方法;然而，单独的免疫隔离仍然允许脱落的供体抗原逃逸到宿主环境中，导致间接抗原识别、免疫细胞活化和毒性移植部位的产生。设计材料以减少抗原逃逸、提高细胞活力和增加材料相容性都是可以减少抗原和危险信号局部释放到植入物微环境中的方法。植入物材料可通过局部递送抗炎剂、抑制剂、趋化剂和/或致耐受剂来进一步增强，所述抗炎剂、抑制剂、趋化剂和/或致耐受剂用于控制对植入物的先天性免疫应答和适应性免疫应答两者，具有降低全身效应的益处。从了解如何操纵胰岛的同种异体和自体免疫反应中获得的经验教训也可以应用于其他细胞疗法，以提高其疗效和持续时间。
The effective suppression of adaptive immune responses is essential for the success of allogeneic cell therapies. In islet transplantation for Type 1 Diabetes, pre-existing autoimmunity provides an additional hurdle, as memory autoimmune T cells mediate both an autoantigen-specific attack on the donor beta cells and an alloantigen-specific attack on the donor graft cells. Immunosuppressive agents used for islet transplantation are generally successful in suppressing alloimmune responses, but dramatically hinder the widespread adoption of this therapeutic approach and fail to control memory T cell populations, which leaves the graft vulnerable to destruction. In this review, we highlight the capacity of biomaterials to provide local and nuanced instruction to suppress or alter immune pathways activated in response to an allogeneic islet transplant. Biomaterial immunoisolation is a common approach employed to block direct antigen recognition and downstream cell-mediated graft destruction; however, immunoisolation alone still permits shed donor antigens to escape into the host environment, resulting in indirect antigen recognition, immune cell activation, and the creation of a toxic graft site. Designing materials to decrease antigen escape, improve cell viability, and increase material compatibility are all approaches that can decrease the local release of antigen and danger signals into the implant microenvironment. Implant materials can be further enhanced through the local delivery of anti-inflammatory, suppressive, chemotactic, and/or tolerogenic agents, which serve to control both the innate and adaptive immune responses to the implant with a benefit of reduced systemic effects. Lessons learned from understanding how to manipulate allogeneic and autogenic immune responses to pancreatic islets can also be applied to other cell therapies to improve their efficacy and duration.
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影响因子：
4.3
作者：
Plenter RJ;Grazia TJ;Nelson DP;Zamora MR;Gill RG;Pietra BA
通讯作者：
Pietra BA
影响因子：
7.7
作者：
Barra, Jessie M.;Kozlovskaya, Veronika;Tse, Hubert M.
通讯作者：
Tse, Hubert M.
影响因子：
3.8
作者：
Buchwald, Peter;Tamayo-Garcia, Alejandro;Stabler, Cherie L.
通讯作者：
Stabler, Cherie L.
DOI：
10.1111/j.1600-6143.2009.02578.x
发表时间：
2009-04
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Brennan TV;Jaigirdar A;Hoang V;Hayden T;Liu FC;Zaid H;Chang CK;Bucy RP;Tang Q;Kang SM
通讯作者：
Kang SM
DOI：
10.1073/pnas.90.8.3373
发表时间：
1993-04-15
影响因子：
11.1
作者：
AUCHINCLOSS, H;LEE, R;GLIMCHER, LH
通讯作者：
GLIMCHER, LH