Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors.
Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors.
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DOI：
10.1016/j.addr.2010.09.013
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发表时间：
2010-09-30
影响因子：
16.1
通讯作者：
Nolta, Jan A.
中科院分区：
文献类型：
--
作者：
Meyerrose, Todd;Olson, Scott;Pontow, Suzanne;Kalomoiris, Stefanos;Jung, Yunjoon;Annett, Geralyn;Bauer, Gerhard;Nolta, Jan A.
关键词：
间充质干细胞 (MSC) 是一种很有前景的细胞治疗工具，可以直接促进骨、肌腱和软骨的修复，也可以通过蛋白质生产和免疫介导作为辅助治疗。由于多种细胞固有的和环境响应的特性，它们是细胞治疗的一种有吸引力的载体。移植后，间充质干细胞能够进行全身迁移，不易形成肿瘤，并且似乎能够耐受供体不匹配的免疫反应。这些属性相结合，使 MSC 能够驻留在许多不同的组织类型中，而不破坏局部微环境，并且在某些情况下，通过适当的蛋白质分泌来响应局部环境。我们描述了我们小组和其他人在使用人类 MSC 持续体内产生超生理水平的细胞因子以支持共移植的造血干细胞和溶酶体贮积症动物模型（例如 MPSVII）中缺乏的酶方面所做的工作。此外，经改造后分泌蛋白质产物的间充质干细胞在组织损伤修复的多个领域的应用也得到了综述，包括但不限于心肌梗塞后的血运重建、椎间盘缺损的再生和脊柱治疗、中风修复、癫痫治疗、骨骼组织修复、软骨形成/膝关节和关节修复以及神经退行性疾病。因此，基因工程间充质干细胞已在众多疾病修饰和组织修复动物模型中被证明是安全有效的，并准备在人体临床试验中进行测试。这些有趣的细胞以持续和长期的方式分泌内源或转基因产物的潜力是非常有前途的，并且在当前的评论中进行了讨论。
Mesenchymal stem cells (MSC) are a promising tool for cell therapy, either through direct contribution to the repair of bone, tendon and cartilage or as an adjunct therapy through protein production and immune mediation. They are an attractive vehicle for cellular therapies due to a variety of cell intrinsic and environmentally responsive properties. Following transplantation, MSC are capable of systemic migration, are not prone to tumor formation, and appear to tolerize the immune response across donor mismatch. These attributes combine to allow MSC to reside in many different tissue types without disrupting the local microenvironment and, in some cases, responding to the local environment with appropriate protein secretion. We describe work done by our group and others in using human MSC for the sustained in vivo production of supraphysiological levels of cytokines for the support of cotransplanted hematopoietic stem cells and enzymes that are deficient in animal models of lysosomal storage disorders such as MPSVII. In addition, the use of MSC engineered to secrete protein products has been reviewed in several fields of tissue injury repair, including but not limited to revascularization after myocardial infarction, regeneration of intervertebral disc defects and spine therapy, repair of stroke, therapy for epilepsy, skeletal tissue repair, chondrogenesis/knee and joint repair, and neurodegenerative diseases. Genetically engineered MSC have thus proven safe and efficacious in numerous animal models of disease modification and tissue repair and are poised to be tested in human clinical trials. The potential for these interesting cells to secrete endogenous or transgene products in a sustained and long-term manner is highly promising and is discussed in the current review.
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DOI：
10.1073/pnas.96.6.2988
发表时间：
1999-03-16
影响因子：
11.1
作者：
Case, SS;Price, MA;Crooks, GM
通讯作者：
Crooks, GM
影响因子：
4.2
作者：
Allay, JA;Dennis, JE;Gerson, SL
通讯作者：
Gerson, SL
影响因子：
20.3
作者：
Almeida-Porada, G;Porada, CD;Zanjani, ED
通讯作者：
Zanjani, ED
影响因子：
15.9
作者：
Bianco, P;Robey, PG
通讯作者：
Robey, PG
影响因子：
5.1
作者：
Eliopoulos, N;Al-Khaldi, A;Galipeau, J
通讯作者：
Galipeau, J