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临床前兔模型中用于尿流改道的组织工程管状替代物

Tissue-engineered tubular substitutions for urinary diversion in a preclinical rabbit model.

作者信息

Wang Qianliang, Liu Qingling

机构信息

Department of Urology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Department of Record Room, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

出版信息

Front Med (Lausanne). 2025 Jun 26;12:1616977. doi: 10.3389/fmed.2025.1616977. eCollection 2025.

Abstract

OBJECTIVE

To develop and evaluate tissue-engineered tubular constructs using homologous adipose-derived stem cells (ASCs), smooth muscle cells (SMCs), and decellularized fish swim bladder (DFSB) matrix for urinary diversion in a rabbit model.

METHODS

Rabbit ASCs and SMCs were isolated and expanded ; cultured cells were seeded onto bilateral surfaces of DFSB scaffolds followed by 7-day incubation; cell-seeded matrices were shaped into tubular constructs; constructs underwent 2-week pre-vascularization within omental pouches. Experimental group rabbits (=24) underwent complete bladder resection with replacement by pre-vascularized constructs, while control group (=6) received identical implantation of acellular DFSB tubes. Histological evaluations were conducted at postoperative weeks 2, 4, 8, and 16; intravenous urography (IVU) was performed at 16-week endpoint.

RESULTS

All experimental animals survived until scheduled sacrifice with histological evidence of: (1) luminal multilayer urothelium, (2) organized smooth muscle tissue on abluminal surfaces, and (3) construct-wide neovascularization of varying diameters; IVU confirmed absence of urinary leakage, stricture, or obstruction. Conversely, all control animals died within 2 weeks post-operation; autopsy revealed urine leakage, extensive scar formation, and severe inflammation as mortality causes.

CONCLUSION

Tissue-engineered tubular constructs fabricated from homologous ASCs, SMCs, and DFSB scaffold demonstrate feasibility as a viable urinary diversion alternative in rabbit models, showing functional tissue regeneration and superior outcomes versus acellular controls.

摘要

目的

利用同源脂肪干细胞(ASCs)、平滑肌细胞(SMCs)和去细胞鱼鳔(DFSB)基质构建并评估用于兔模型尿路改道的组织工程管状结构。

方法

分离并扩增兔ASCs和SMCs;将培养的细胞接种到DFSB支架的双侧表面,随后孵育7天;将接种细胞的基质制成管状结构;将结构在网膜囊内进行2周的预血管化处理。实验组兔(n = 24)接受全膀胱切除并用预血管化结构替代,而对照组(n = 6)接受相同的无细胞DFSB管植入。在术后第2、4、8和16周进行组织学评估;在16周终点进行静脉尿路造影(IVU)。

结果

所有实验动物均存活至预定处死,组织学证据显示:(1)腔内多层尿路上皮,(2)腔外表面有组织化的平滑肌组织,(3)整个结构有不同直径的新生血管形成;IVU证实无尿漏、狭窄或梗阻。相反,所有对照动物在术后2周内死亡;尸检显示尿漏、广泛瘢痕形成和严重炎症是死亡原因。

结论

由同源ASCs、SMCs和DFSB支架构建的组织工程管状结构在兔模型中证明了作为可行的尿路改道替代方案的可行性,显示出功能性组织再生且与无细胞对照组相比结果更佳。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4df/12241010/abae5dc3e518/fmed-12-1616977-g001.jpg

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