Bury Matthew I, Fuller Natalie J, Wethekam Linnea, Sharma Arun K
Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, USA.
Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, USA ; Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL, USA ; Northwestern University, Simpson Querrey Institute for BioNanotechnology, Chicago, IL, USA ; Northwestern University, Department of Biomedical Engineering, Evanston, IL, USA.
Cent European J Urol. 2015;68(1):115-20. doi: 10.5173/ceju.2015.01.526. Epub 2015 Jan 24.
Inflammatory responses following tissue injury are essential for proper tissue regeneration. However, dysfunctional or repetitive inflammatory tissue assaults can lead to poor tissue regeneration and ultimate tissue failure via fibrosis. Previous attempts at urinary bladder tissue regeneration utilizing polymeric and biologic scaffolding materials tended to elicit these responses leading to poor tissue regeneration. Recent advances in bladder regeneration utilizing bone marrow derived mesenchymal stem cells (MSCs) and CD34(+) hematopoietic stem/progenitor cells (HSPCs) with biocompatible citric acid based scaffolds have provided an environment that not only promotes the growth of architecturally germane and physiologically functional tissue, but also modulates aspects of the innate immune response.
Within this study MSCs, CD34(+) HSPCs, or MSC/CD34(+) HSPC seeded POC [poly (1,8-octanediol-co-citrate)] scaffolds were utilized in an established rodent bladder augmentation model to evaluate inflammation as it pertains to bladder tissue regeneration.
Quantified data from post-augmentation regenerated tissue samples at the 4 week time-point demonstrated that POC/MSC and POC/MSC + CD34(+) HSPC grafts markedly reduced the presence of pro-inflammatory CD68(+) macrophages and MPO(+) neutrophils compared to unseeded POC or POC/CD34(+) HSPC-only seeded grafts. Pro-inflammatory cytokines TNFα and IL-1b were also significantly down-regulated with a concomitant increase in the anti-inflammatory cytokines IL-10 and IL-13 in the aforementioned POC/MSC and POC/MSC + CD34(+) HSPC composites. Furthermore, this led to fewer instances of bladder tissue granuloma formation combined with greater muscle content and tissue angiogenic events as previous data has demonstrated.
Data indicates that POC/MSC and POC/MSC + CD34(+) HSPC grafts attenuate the innate inflammatory response and promote bladder tissue regeneration.
组织损伤后的炎症反应对于组织的正常再生至关重要。然而，功能失调或反复的炎症组织攻击可通过纤维化导致组织再生不良和最终的组织衰竭。以往利用聚合物和生物支架材料进行膀胱组织再生的尝试往往引发这些反应，导致组织再生不良。利用骨髓间充质干细胞（MSC）和CD34(+)造血干/祖细胞（HSPC）与生物相容性柠檬酸基支架进行膀胱再生的最新进展提供了一种环境，不仅能促进结构相关且生理功能正常的组织生长，还能调节先天免疫反应的各个方面。
在本研究中，将MSC、CD34(+) HSPC或接种了MSC/CD34(+) HSPC的聚（1,8 - 辛二醇 - 共 - 柠檬酸）（POC）支架用于已建立的啮齿动物膀胱扩大模型，以评估与膀胱组织再生相关的炎症情况。
在4周时间点对扩大术后再生组织样本的定量数据表明，与未接种的POC或仅接种POC/CD34(+) HSPC的移植物相比，POC/MSC和POC/MSC + CD34(+) HSPC移植物显著减少了促炎CD68(+)巨噬细胞和MPO(+)中性粒细胞的存在。在上述POC/MSC和POC/MSC + CD34(+) HSPC复合材料中，促炎细胞因子TNFα和IL - 1b也显著下调，同时抗炎细胞因子IL - 10和IL - 13增加。此外，如先前数据所示，这导致膀胱组织肉芽肿形成的情况减少，同时肌肉含量和组织血管生成事件增加。
数据表明POC/MSC和POC/MSC + CD34(+) HSPC移植物可减轻先天炎症反应并促进膀胱组织再生。
