Early cellular and stromal responses in regeneration versus repair of a mammalian bladder using autologous cell and biodegradable scaffold technologies
Early cellular and stromal responses in regeneration versus repair of a mammalian bladder using autologous cell and biodegradable scaffold technologies
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DOI：
10.1016/j.juro.2008.02.039
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发表时间：
2008-07-01
影响因子：
6.6
通讯作者：
Bertram, Timothy A.
中科院分区：
文献类型：
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作者：
Jayo, Manuel J.;Jain, Deepak;Bertram, Timothy A.
目的：内脏器官再生有望改变医疗技术和减少器官短缺。目前内脏器官衰竭的治疗主要局限于器官移植。由合成生物聚合物和自体细胞组成的结构已在接受膀胱扩大成形术的患者中显示出长期临床益处。然而，据我们所知，膀胱再生过程中的早期细胞和基质事件尚未阐明。 材料和方法：对 2 个生物聚合物植入物的原位细胞反应，包括基于聚乳酸-乙醇酸 (Sigma-Aldrich (TM)) 的可生物降解网状支架，具有自体尿路上皮和平滑肌细胞（构建体）和基于聚（乳酸-乙醇酸）的可生物降解网状支架，不含细胞（支架），在膀胱增强成形术的犬模型中进行比较。愈合事件与尿动力学评估相关。结果：构建植入物早在植入后 4 个月就恢复了基线尿动力学。支架植入后的尿动力学在 9 个月时研究终止时未能恢复到基线。构建体和支架植入物引起的功能差异与新组织的结构差异相关。构建基质具有更大的血管化，具有轻轻折叠、交织的结缔组织成分。支架基质是致密的、随意组织的结缔组织。尿路上皮响应构建体和支架植入而再生。然而，只有构建体在早期时间点具有正常的基质、发育良好的逼尿肌和丰富的α-平滑肌肌动蛋白（Vector Laboratories，Burlingame，加利福尼亚州）细胞染色，导致在 9 个月时结构和功能完整的再生膀胱壁。结论：早期细胞和基质事件区分导致膀胱壁再生或修复的愈合过程。含有细胞的构建植入物引发早期愈合过程，最终导致完整粘膜和肌肉成分的再生，而对支架植入的反应与修复性愈合一致，即粘膜生长但组织层发育不完整。
Purpose: Internal organ regeneration holds promise for changing medical technology and decreasing organ shortages. Current medical treatment for internal organ failure is largely limited to organ transplantation. A construct composed of synthetic biopolymer with autologous cells has shown long-term clinical benefit in patients undergoing augmentation cystoplasty. However, to our knowledge early cellular and stromal events during bladder regeneration have not been elucidated.Materials and Methods: In situ cellular responses to 2 biopolymer implants, including a poly(lactic-co-glycolic acid) (Sigma-Aldrich (TM)) based biodegradable mesh scaffold with autologous urothelial and smooth muscle cells (construct) and a poly(lactic-co-glycolic acid) based biodegradable mesh scaffold alone without cells (scaffold), were compared in a canine model of augmentation cystoplasty. Healing events were correlated with urodynamic assessments.Results: Construct implants regenerated baseline urodynamics as early as 4 months after implantation. Urodynamics following scaffold implantation failed to return to baseline by study termination at 9 months. Functional differences elicited by construct and scaffold implants correlated with structural differences in the neotissues. Construct stroma had greater vascularization with gently folded, interwoven connective tissue elements. Scaffold stroma was dense, haphazardly organized connective tissue. Urothelium regenerated in response to construct and scaffold implantation. However, only construct had normal stroma, well developed detrusor and abundant a-smooth muscle actin (Vector Laboratories, Burlingame, California) cell staining at early time points, leading to a structurally and functionally complete regenerated bladder wall at 9 months.Conclusions: Early cellular and stromal events distinguish healing processes that lead to bladder wall regeneration or repair. Construct implants containing cells elicit early healing processes that culminate with the regeneration of complete mucosal and muscular components, whereas the response to scaffold implantation is consistent with reparative healing, that is with mucosal growth but incomplete tissue layer development.