Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells.
Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells.
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DOI：
10.1038/s41598-017-09115-2
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发表时间：
2017-08-16
影响因子：
4.6
通讯作者：
Nagayasu T
中科院分区：
文献类型：
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作者：
Doi R;Tsuchiya T;Mitsutake N;Nishimura S;Matsuu-Matsuyama M;Nakazawa Y;Ogi T;Akita S;Yukawa H;Baba Y;Yamasaki N;Matsumoto K;Miyazaki T;Kamohara R;Hatachi G;Sengyoku H;Watanabe H;Obata T;Niklason LE;Nagayasu T
由脱细胞的肺支架组成的生物工程肺可以在未来提供急需的捐赠器官，这种支架可以重新填充患者自己的细胞。这种方法已经在大鼠身上进行了测试，并在猪和人的肺中进行了部分探索。然而，现有的生物工程肺是脆弱的，部分原因是它们的血管结构不成熟。在此，我们报道了脂肪来源的干细胞/基质细胞(ASCs)在脱细胞大鼠肺支架中构建肺血管的应用。我们发现，预接种的ASCs分化为周细胞，并稳定新生肺血管内皮细胞(EC)单层，从而有助于EC在再生肺中的存活。在原位移植模型中，ASC介导的内皮细胞稳定明显降低了血管通透性，并抑制了肺泡出血，最长可达3 h。成纤维细胞生长因子9是一种间质靶向生长因子，可促进ASC向周细胞分化，但过度刺激其增殖，导致再生肺中血管系统的部分阻塞。因此，ASCs可能为生物工程肺的血管再生提供一个有前途的细胞来源，尽管还需要额外的工作来优化器官培养的生长因子或激素环境。
Bioengineered lungs consisting of a decellularized lung scaffold that is repopulated with a patient’s own cells could provide desperately needed donor organs in the future. This approach has been tested in rats, and has been partially explored in porcine and human lungs. However, existing bioengineered lungs are fragile, in part because of their immature vascular structure. Herein, we report the application of adipose-derived stem/stromal cells (ASCs) for engineering the pulmonary vasculature in a decellularized rat lung scaffold. We found that pre-seeded ASCs differentiated into pericytes and stabilized the endothelial cell (EC) monolayer in nascent pulmonary vessels, thereby contributing to EC survival in the regenerated lungs. The ASC-mediated stabilization of the ECs clearly reduced vascular permeability and suppressed alveolar hemorrhage in an orthotopic transplant model for up to 3 h after extubation. Fibroblast growth factor 9, a mesenchyme-targeting growth factor, enhanced ASC differentiation into pericytes but overstimulated their proliferation, causing a partial obstruction of the vasculature in the regenerated lung. ASCs may therefore provide a promising cell source for vascular regeneration in bioengineered lungs, though additional work is needed to optimize the growth factor or hormone milieu for organ culture.