Hypoxia-Preconditioned Adipose-Derived Endothelial Progenitor Cells Promote Bladder Augmentation
| Autor: | Ruipeng Jia, Lu-Wei Xu, Liuhua Zhou, Min Wang, Zhongle Xu, Wenwen Ping, Feng Zhao, Changcheng Zhou, Jingyu Liu, Zheng Xu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Angiogenesis
medicine.medical_treatment Urinary Bladder 0206 medical engineering Biomedical Engineering Bioengineering 02 engineering and technology Biochemistry Biomaterials Cystectomy 03 medical and health sciences chemistry.chemical_compound Tissue engineering Cell Movement Animals Medicine Urothelium Progenitor cell Cell Proliferation Endothelial Progenitor Cells 030304 developmental biology 0303 health sciences Tissue Engineering business.industry food and beverages Muscle Smooth Flow Cytometry Immunohistochemistry 020601 biomedical engineering Vascular endothelial growth factor chemistry Bladder augmentation Cancer research Stem cell business |
| Zdroj: | Tissue Engineering Part A. 26:78-92 |
| ISSN: | 1937-335X 1937-3341 |
| Popis: | Tissue engineering technology provides an alternative for bladder reconstruction, which remains confronted with challenges, such as insufficient vascularization in regenerated bladder tissue. Short-term hypoxic preconditioning has been reported to be an effective method to enhance the angiogenic effect of stem cells. This study evaluated the effect and mechanism of hypoxia-preconditioned adipose-derived endothelial progenitor cells (hp-ADEPCs) on the vascularization and smooth muscle regeneration of tissue-engineered bladders. Rats were randomly divided into the following four groups: hp-ADEPC, ADEPC, bladder acellular matrix (BAM), and cystotomy groups. A partial cystectomy was performed to remove 50% of the bladder, which was augmented with hp-ADEPC-BAM, ADEPC-BAM, or BAM. Histological and functional assessments of the engineered neobladder were performed at 1 and 3 months after surgery, while the mechanism of hp-ADEPCs on vascularization was also investigated. Immunohistochemical analysis revealed that hp-ADEPC-BAM significantly promoted urothelium, blood vessel, smooth muscle, and nerve cell regeneration. Animals in the hp-ADEPC-BAM group exhibited higher bladder compliance and a relatively normal micturition pattern compared with the ADEPC-BAM and BAM groups. In addition, compared with ADEPCs, hp-ADEPCs promoted ERK phosphorylation activation and hypoxia-inducible factor-1α expression, thereby secreting more vascular endothelial growth factor and basic fibroblast growth factor and significantly enhancing the migration and angiogenesis abilities of rat endothelial cells. This is the first study to demonstrate that a combination of ADEPCs and BAM with short-term hypoxic preconditioning enhances angiogenesis and promotes the functional recovery of tissue-engineered bladders. Impact Statement Insufficient vascularization in regenerated bladder tissue remains a challenge for bladder tissue engineering. We successfully isolated adipose-derived endothelial progenitor cells (ADEPCs) with high proliferative potential and angiogenic properties. Hypoxic preconditioning was confirmed to effectively enhance stem cell activity. In this study, a porcine bladder acellular matrix (BAM) was established, and hypoxia-preconditioned autologous ADEPCs were simultaneously introduced for bladder reconstruction in a rat model, followed by an assessment of their feasibility and potential for bladder vascularization. For the first time, we demonstrated that hypoxic preconditioning of ADEPCs improves angiogenesis and the functional recovery of tissue-engineered bladders. |
| Databáze: | OpenAIRE |
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