Progress in myoblast transplantation: a potential treatment of dystrophies

Progress in myoblast transplantation: a potential treatment of dystrophies
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成肌细胞移植的进展:营养不良的潜在治疗方法

DOI:
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发表时间:
2000
期刊:
Microscopy research and technique (Print)
影响因子:
--
通讯作者:
J. Tremblay
J. Tremblay
中科院分区:
--
文献类型:
--
作者:
D. Skuk;J. Tremblay

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成肌细胞移植(MT)包括将正常或转基因的肌原细胞注射到肌肉中,预计它们会在肌肉中融合并形成成熟的纤维。作为治疗严重遗传性肌肉疾病的实验方法,MT 于 20 世纪 90 年代初在营养不良患者中进行了测试。尽管这些早期的临床试验并不成功,但MT通过动物模型的研究取得了进展。在过去的几年里,人们发现了许多影响机器翻译成功的因素。本综述更新了我们对 MT 的了解,并描述了限制其成功的不同问题。最初被低估的因素,例如 MT 后的特异性免疫反应,目前已得到很好的表征。 MT 后,活化的 T 淋巴细胞对混合纤维的破坏以及针对移植的成肌细胞的抗体的产生是导致移植物排斥的原因。免疫抑制剂的选择似乎非常重要,FK506 是已知的最好的药物,可以在 MT 后获得最佳结果。在 FK506 免疫抑制下,在小鼠和猴子中均获得了非常有效的 MT。此外,在营养不良小鼠中,结果表明 MT 可以改善该疾病的一些表型特征。目前正在研究移植细胞的存活率的提高以及它们向注射组织的迁移的增加。目前的一些研究还旨在通过使用患者自身的细胞进行 MT 来绕过免疫抑制。从这个意义上说,在MT前将正常基因导入患者的成肌细胞,提高这些细胞的体外增殖能力。微型。资源。技术。 48:213–222, 2000。© 2000 Wiley‐Liss, Inc.
Myoblast transplantation (MT) consists of injecting normal or genetically modified myogenic cells into muscles, where they are expected to fuse and form mature fibers. As an experimental approach to treat severe genetic muscle diseases, MT was tested in dystrophic patients at the beginning of the 1990s. Although these early clinical trials were unsuccessful, MT has progressed through the research on animal models. Many factors that may condition the success of MT were identified in the last years. The present review updates our knowledge on MT and describes the different problems that have limited its success. Factors that were first underestimated, like the specific immune response after MT, are presently well characterized. Destruction of the hybrid fibers by activated T‐lymphocytes and production of antibodies against the transplanted myoblasts take place after MT and are responsible for the graft rejection. The choice of the immunosuppression seems to be very important, and FK506 is the best agent known to allow the best results after MT. Under FK506 immunosuppression, very efficient MT were obtained both in mice and monkeys. Moreover, in dystrophic mice it was demonstrated that MT ameliorates some phenotypical characteristics of the disease. The improvement of the survival of the transplanted cells and the increase of their migration into the injected tissue are presently under investigation. Some of the present research is directed also to bypass the immunosuppression by using the patient's own cells for MT. In this sense, efforts are conducted to introduce the normal gene into the patient's myoblasts before MT and to improve the ability of these cells to proliferate in vitro. Micros. Res. Tech. 48:213–222, 2000. © 2000 Wiley‐Liss, Inc.
将基因标记的骨骼肌母细胞动脉输送至小鼠心脏:植入的成肌细胞的长期存活和表型修饰。
DOI: 10.1177/096368979600500113
发表时间: 1996
影响因子: 3.3
作者:
Robinson,SW;Cho,PW;Levitsky,HI;Olson,JL;Hruban,RH;Acker,MA;Kessler,PD
通讯作者: Kessler,PD
DOI: 10.1056/nejm199509283331303
发表时间: 1995-09-28
影响因子: 158.5
作者:
MENDELL, JR;KISSEL, JT;BURGHES, AHM
通讯作者: BURGHES, AHM
DOI: 10.1126/science.1962213
发表时间: 1991-12-06
期刊: SCIENCE
影响因子: 56.9
作者:
DHAWAN, J;PAN, LC;BLAU, HM
通讯作者: BLAU, HM
端粒的实验延长延长了永生细胞与正常细胞杂交体的寿命。
DOI: --
发表时间: 1996
期刊: The EMBO journal
影响因子: --
作者:
Wright,WE;Brasiskyte,D;Piatyszek,MA;Shay,JW
通讯作者: Shay,JW
植入的成肌细胞不仅与肌纤维融合,而且作为肌肉前体细胞存活。
DOI: 10.1242/jcs.105.4.957
发表时间: 1993
影响因子: 4
作者:
Yao,SN;Kurachi,K
通讯作者: Kurachi,K