Bioengineering of Physiologically Functional Intrinsically Innervated Human Internal Anal Sphincter Constructs
Bioengineering of Physiologically Functional Intrinsically Innervated Human Internal Anal Sphincter Constructs
复制标题
DOI：
10.1089/ten.tea.2013.0422
复制
发表时间：
2014-06-01
影响因子：
4.1
通讯作者：
Bitar, Khalil N.
中科院分区：
文献类型：
--
作者：
Gilmont, Robert R.;Raghavan, Shreya;Bitar, Khalil N.
肌肉替代患者遭受广泛的组织损失或功能障碍是再生医学的一个主要目标。为了达到功能状态，生物工程肌肉替代结构需要神经支配。在这里，我们描述了一种方法，生物工程的功能神经支配的肠平滑肌结构使用神经元祖细胞和平滑肌细胞分离和培养的肠组织的成年人供体。这些构建体表达收缩平滑肌、神经胶质细胞和成熟神经元群体的标记物。该结构适当地响应生理相关的神经递质，和神经网络的整合证明了电场刺激的反应。肠神经祖细胞分化成神经元群体的能力为除肠外的各种生物工程肌肉结构的功能性神经支配提供了巨大的潜力。功能性神经支配肌肉结构为创伤或退行性疾病后的神经肌肉置换提供了一种基于再生医学的治疗方法。
Muscle replacement for patients suffering from extensive tissue loss or dysfunction is a major objective of regenerative medicine. To achieve functional status, bioengineered muscle replacement constructs require innervation. Here we describe a method to bioengineer functionally innervated gut smooth muscle constructs using neuronal progenitor cells and smooth muscle cells isolated and cultured from intestinal tissues of adult human donors. These constructs expressed markers for contractile smooth muscle, glial cells, and mature neuronal populations. The constructs responded appropriately to physiologically relevant neurotransmitters, and neural network integration was demonstrated by responses to electrical field stimulation. The ability of enteric neuroprogenitor cells to differentiate into neuronal populations provides enormous potential for functional innervation of a variety of bioengineered muscle constructs in addition to gut. Functionally innervated muscle constructs offer a regenerative medicine-based therapeutic approach for neuromuscular replacement after trauma or degenerative disorders.