Progress and challenges in the development of a cell-based therapy for hemophilia A.
Progress and challenges in the development of a cell-based therapy for hemophilia A.
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DOI：
10.1111/jth.12750
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Muench MO
中科院分区：
文献类型：
--
作者：
Fomin ME;Togarrati PP;Muench MO
A 型血友病是由于 VIII 因子 (FVIII) 缺乏所致。虽然血浆来源或重组 FVIII 的替代疗法对于 A 型血友病患者来说是一种挽救生命的疗法，但这种疗法是一种终生治疗，而不是治愈该疾病。在这篇综述中，我们讨论了 A 型血友病细胞疗法的发展中仍然存在的可能性、进展和挑战。细胞疗法的成功取决于供体细胞的类型和可用性、宿主的年龄和移植方法，以及移植物的植入和产生 FVIII 的水平。早期治疗，甚至可能是产前移植，可以通过避免移植物的免疫排斥来产生最高水平的植入。 FVIII 的潜在细胞来源包括成人和胎儿肝脏中存在的称为肝窦内皮细胞 (LSEC) 的特殊内皮细胞亚群，或源自经过基因编辑产生 FVIII 的诱导多能干细胞 (iPSC) 的患者特异性内皮细胞。实现移植 LSEC 的充分植入是血友病 A 细胞治疗成功的障碍之一。我们讨论了动物移植的最新结果，这些结果显示从供体 LSEC 获得的功能性和临床相关水平的 FVIII 的产生。因此，通过从许多潜在细胞来源的移植供体细胞持续产生 FVIII，或通过从患者特异性 iPSC 产生供体内皮细胞，可以预见治疗 A 型血友病的可能性。
Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review we discuss the possibilities, progress and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells (iPSCs) that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific iPSCs.
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影响因子：
0.9
作者：
Gupta, D. K.;Sharma, S.;Dattagupta, S.
通讯作者：
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影响因子：
29.4
作者：
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影响因子：
20.3
作者：
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通讯作者：
Montgomery, Robert R.
DOI：
10.1073/pnas.0607012103
发表时间：
2006-12-12
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.8
作者：
Golfier, F;Bárcena, A;Muench, MO
通讯作者：
Muench, MO