Unlocking the post-transplant microenvironment for successful islet function and survival.
Unlocking the post-transplant microenvironment for successful islet function and survival.
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DOI：
10.3389/fendo.2023.1250126
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
胰岛移植（IT）为1型糖尿病（T1DM）患者提供了恢复功能的可能性。尽管胰岛分离技术和免疫抑制方案有所改进，但结果仍不理想，英国5年移植物存活率（5YGS）为55%，大多数患者在多次胰岛输注后仍需要外源性胰岛素。天然胰岛具有重要的非内分泌成分，具有致密的细胞外基质（ECM），对胰岛发育、细胞存活和功能很重要。胶原酶分离必然会破坏这种复杂的胰岛微环境，使胰岛缺乏支撑框架，增加移植胰岛的脆弱性。在门静脉移植后，可能诱导肝损伤反应，这通常导致炎症和来自肝特异性肌成纤维细胞的ECM沉积。这种反应的影响可能对胰岛存活和功能有重要影响。在肾包膜和眼腔以及其他植入部位的成纤维细胞反应和ECM沉积已被证明有利于存活和功能。研究植入部位微环境和移植胰岛与ECM蛋白的相互作用可以揭示改善IT和干细胞衍生的β细胞疗法的治疗干预。
Islet transplantation (IT) offers the potential to restore euglycemia for patients with type 1 diabetes mellitus (T1DM). Despite improvements in islet isolation techniques and immunosuppressive regimes, outcomes remain suboptimal with UK five-year graft survivals (5YGS) of 55% and most patients still requiring exogenous insulin after multiple islet infusions. Native islets have a significant non-endocrine component with dense extra-cellular matrix (ECM), important for islet development, cell survival and function. Collagenase isolation necessarily disrupts this complex islet microenvironment, leaving islets devoid of a supporting framework and increasing vulnerability of transplanted islets. Following portal venous transplantation, a liver injury response is potentially induced, which typically results in inflammation and ECM deposition from liver specific myofibroblasts. The impact of this response may have important impact on islet survival and function. A fibroblast response and ECM deposition at the kidney capsule and eye chamber alongside other implantation sites have been shown to be beneficial for survival and function. Investigating the implantation site microenvironment and the interactions of transplanted islets with ECM proteins may reveal therapeutic interventions to improve IT and stem-cell derived beta-cell therapy.
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影响因子：
8.2
作者：
Gibly, R. F.;Graham, J. G.;Luo, X.;Lowe, W. L., Jr.;Hering, B. J.;Shea, L. D.
通讯作者：
Shea, L. D.
影响因子：
11.1
作者：
Athwal VS;Pritchett J;Llewellyn J;Martin K;Camacho E;Raza SM;Phythian-Adams A;Birchall LJ;Mullan AF;Su K;Pearmain L;Dolman G;Zaitoun AM;Friedman SL;MacDonald A;Irving WL;Guha IN;Hanley NA;Piper Hanley K
通讯作者：
Piper Hanley K
影响因子：
4.6
作者：
Friedman-Mazursky O;Elkon R;Efrat S
通讯作者：
Efrat S
影响因子：
15.9
作者：
ALEJANDRO, R;CUTFIELD, RG;MINTZ, DH
通讯作者：
MINTZ, DH
影响因子：
7.7
作者：
Brissova, M;Fowler, M;Powers, AC
通讯作者：
Powers, AC