Kwon Tae Gyun, Yoo James J, Atala Anthony
Department of Urology and Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27154-1094, USA.
J Urol. 2008 May;179(5):2035-41. doi: 10.1016/j.juro.2008.01.005. Epub 2008 Mar 19.
Tissue engineered bladders are emerging as a potential treatment option in urological surgery. Although successful neobladders can be engineered with autologous cells on a biodegradable polymer scaffold, studies of the local and systemic effects on host tissue have not been extensively pursued. We examined such effects at predetermined time points after implantation of tissue engineered neobladders in a canine cystoplasty model.
Eight dogs underwent trigone sparing cystectomies. Six dogs (experimental group) received bladder augmentation with tissue engineered constructs produced from autologous urothelial and smooth muscle cells on a prefabricated polyglycolic acid polymer scaffold. Two beagles (control group) received bladder augmentation with the polyglycolic acid scaffold alone. Serial urodynamic studies, cystograms, peripheral blood smears, urinalysis, serum chemistry, complete blood count and electrolytes were done at predetermined time points postoperatively. The bladder, and local and distant organs were retrieved 6 months after surgery for analysis.
Capacity and compliance of the engineered bladders reached normal levels by 6 months. Engineered bladders showed tissue composition similar to that of normal bladders. Infiltration of inflammatory cells was minimal and subsided with time. An increase in the total systemic leukocyte count and in bacteriuria was evident initially at 1 week but they returned to normal levels by 1 month postoperatively. Other systemic parameters remained within normal levels at all time points. There was no evidence of abnormal findings in local or distant organs.
Implantation of polymer molds seeded with autologous bladder cells did not show significant local or systemic toxicity in a canine model. This study suggests that such engineered neobladders are safe and effective for reconstructive surgery.
组织工程膀胱正逐渐成为泌尿外科手术中的一种潜在治疗选择。尽管可以使用可生物降解聚合物支架上的自体细胞构建出成功的新膀胱，但对宿主组织的局部和全身影响的研究尚未广泛开展。我们在犬膀胱扩大成形术模型中植入组织工程新膀胱后的预定时间点检查了这些影响。
八只犬接受了保留三角区的膀胱切除术。六只犬（实验组）接受了用预制聚乙醇酸聚合物支架上的自体尿路上皮和平滑肌细胞构建的组织工程构建体进行膀胱扩大术。两只比格犬（对照组）仅接受了聚乙醇酸支架膀胱扩大术。在术后预定时间点进行系列尿动力学研究、膀胱造影、外周血涂片、尿液分析、血清化学、全血细胞计数和电解质检查。术后6个月取出膀胱以及局部和远处器官进行分析。
到6个月时，工程化膀胱的容量和顺应性达到正常水平。工程化膀胱显示出与正常膀胱相似的组织组成。炎性细胞浸润极少，并随时间消退。术后1周时全身白细胞总数和菌尿症最初明显增加，但术后1个月时恢复到正常水平。所有时间点的其他全身参数均保持在正常水平内。局部或远处器官均未发现异常。
在犬模型中，植入接种自体膀胱细胞的聚合物模具未显示出明显的局部或全身毒性。本研究表明，这种工程化新膀胱用于重建手术是安全有效的。
