Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States; Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Winston-Salem, United States.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States; Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Winston-Salem, United States.
Biomaterials. 2014 Feb;35(6):1882-9. doi: 10.1016/j.biomaterials.2013.11.049. Epub 2013 Dec 7.
Neuromuscular disorders of the gut result in disturbances in gastrointestinal transit. The objective of this study was to evaluate the neo-innervation of smooth muscle in an attempt to restore lost innervation. We have previously shown the potential use of composite chitosan scaffolds as support for intestinal smooth muscle constructs. However, the constructs lacked neuronal component. Here, we bioengineered innervated colonic smooth muscle constructs using rabbit colon smooth muscle and enteric neural progenitor cells. We also bioengineered smooth muscle only tissue constructs using colonic smooth muscle cells. The constructs were placed next to each other around tubular chitosan scaffolds and left in culture. Real time force generation conducted on the intrinsically innervated smooth muscle constructs showed differentiated functional neurons. The bioengineered smooth muscle only constructs became neo-innervated. The neo-innervation results were confirmed by immunostaining assays. Chitosan supported (1) the differentiation of neural progenitor cells in the constructs and (2) the neo-innervation of non-innervated smooth muscle around the same scaffold.
肠道的神经肌肉疾病导致胃肠传输紊乱。本研究的目的是评估平滑肌的新生神经支配，试图恢复丧失的神经支配。我们之前已经证明了复合壳聚糖支架作为肠平滑肌构建物的支持物的潜在用途。然而，这些构建物缺乏神经元成分。在这里，我们使用兔结肠平滑肌和肠神经前体细胞来生物工程化有神经支配的结肠平滑肌构建物。我们还使用结肠平滑肌细胞生物工程化仅平滑肌组织构建物。将构建物彼此相邻地放置在管状壳聚糖支架周围，并进行培养。对固有神经支配的平滑肌构建物进行实时力生成实验显示出分化的功能性神经元。生物工程化的仅平滑肌构建物被新生神经支配。免疫染色测定证实了新生神经支配的结果。壳聚糖支持：(1)构建物中神经前体细胞的分化；(2)同一支架周围未受神经支配的平滑肌的新生神经支配。
