Kirpatovckii V I, Kamalov D M, Efimenko A Yu, Makarevich P I, Sagaradze G D, Makarevich O A, Nimiritskii P P, Osidak E O, Domogatskii S P, Karpov V K, Akopyan Z H A, Tkachuk V A, Kamalov A A
Medical Scientific Educational Center of M.V. Lomonosov Moscow State University, Moscow.
N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology branch of P. A. Herzen Federal Medical Research Center of Minzdrav of Russia, Moscow.
Urologiia. 2016 Dec(6):34-42.
Despite the widespread use of intestinal cystoplasty, urinary bladder substitution remains a challenging problem due to the complexity of operations and the potentially high risk of complications. A promising alternative may be bio-engineered collagen-based matrices containing stem cells or their secretions.
To evaluate the effectiveness of this bladder substitution modality, an experiment was conducted on 14 male rabbits. The animals underwent resection of urinary bladder, and the formed defect was substituted with a membrane of type I collagen (series 1, 5 rabbits) or a membrane of the same composition containing a conditioned medium with secretion of mesenchymal stem/stromal cells derived from human adipose tissue (series 2, 5 rabbits). In the comparison group (4 rabbits) resection of the bladder and the closure of the defect was carried out without bladder substitution (series 3).
At 1 month after surgery, there was a complete epithelization of the inner surface of the implant, and body tissues replaced the collagen matrix. In series 1, the collagen implant was replaced mainly by connective tissue ingrown with occasional solitary smooth muscle cells. In series 2, the newly formed bladder wall contained numerous smooth muscle cells, growing into the collagen matrix and forming the muscular coat. In series 3, the muscular layer regeneration at the scar site was also noted, but it was less intense, which was confirmed by morphometry. In series 2, more active vascularization of the collagen implant occurred due to neo-angiogenesis, which was more intense than that in series 3, and especially in series 1. Functional studies revealed a reduced bladder functional capacity in series 1 and 3, while in series 2 it was close to normal. During filling cystometry, changes in intra-vesical pressure profile in series 2 were close to normal, while in series 1 and 3 infusion of a small volume of saline resulted in a marked increase in intra-vesical pressure, showing a reduced compliance of the reconstructed bladder. Discussion The study findings show that implants based on type I collagen can be effectively used to substitute a part of the urinary bladder wall, but bio-engineered collagen matrix grafts containing cell regeneration stimulants secreted by stem cells in their culture medium seem to be more promising.
尽管肠道膀胱扩大术已广泛应用,但由于手术复杂且并发症风险可能较高,膀胱替代仍是一个具有挑战性的问题。一种有前景的替代方法可能是含有干细胞或其分泌物的生物工程胶原蛋白基基质。
为评估这种膀胱替代方式的有效性,对14只雄性兔子进行了实验。动物接受膀胱切除术,形成的缺损用I型胶原蛋白膜(第1组,5只兔子)或含有源自人脂肪组织的间充质干/基质细胞分泌物的条件培养基的相同成分的膜(第2组,5只兔子)替代。在对照组(4只兔子)中,进行膀胱切除术并关闭缺损,不进行膀胱替代(第3组)。
术后1个月,植入物内表面完全上皮化,身体组织替代了胶原蛋白基质。在第1组中,胶原蛋白植入物主要被长入的结缔组织替代,偶尔有孤立的平滑肌细胞。在第2组中,新形成的膀胱壁含有大量平滑肌细胞,长入胶原蛋白基质并形成肌层。在第3组中,也观察到瘢痕部位的肌层再生,但程度较轻,形态计量学证实了这一点。在第2组中,由于新生血管形成,胶原蛋白植入物的血管化更活跃,比第3组更强烈,尤其是比第1组更强烈。功能研究显示,第1组和第3组的膀胱功能容量降低,而第2组接近正常。在充盈膀胱测压期间,第2组膀胱内压曲线的变化接近正常,而在第1组和第3组中,注入少量盐水会导致膀胱内压显著升高,表明重建膀胱的顺应性降低。讨论研究结果表明,基于I型胶原蛋白的植入物可有效用于替代部分膀胱壁,但含有干细胞在其培养基中分泌的细胞再生刺激剂的生物工程胶原蛋白基质移植物似乎更有前景。