Sharma Tiffany T, Edassery Seby L, Rajinikanth Natchiket, Karra Vikram, Bury Matthew I, Sharma Arun K
Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL 60611, USA.
Stanley Manne Children's Research Institute, Chicago, IL 60611, USA.
bioRxiv. 2023 Aug 31:2023.08.29.554824. doi: 10.1101/2023.08.29.554824.
Urinary bladder insult can be caused by environmental, genetic, and developmental factors. Depending upon insult severity, the bladder may lose its ability to maintain capacity and intravesical pressures resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is employed to increase bladder capacity to preserve renal function using autologous bowel tissue as a "patch." To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) with CD34+ hematopoietic stem/progenitor cells (HSPCs) co-seeded onto a pliable synthetic scaffold [POCO; poly(1,8-octamethylene-citrate-co-octanol)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in a baboon bladder augmentation model. We set out to determine the protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogenous protein expression between the tissues following long-term engraftment. We posit that stem cell seeded scaffolds can recapitulate tissue that is almost indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.
膀胱损伤可能由环境、遗传和发育因素引起。根据损伤的严重程度,膀胱可能会失去维持容量和膀胱内压力的能力,从而导致肾功能恶化。膀胱扩大肠囊成形术(BAE)用于通过使用自体肠组织作为“补片”来增加膀胱容量以保护肾功能。为了避免与该手术相关的临床并发症,我们设计了复合移植物,该移植物由自体骨髓间充质干细胞(MSC)与CD34 +造血干/祖细胞(HSPC)共同接种到柔韧的合成支架[POCO;聚(1,8 - 辛亚甲基 - 柠檬酸 - 共 - 辛醇)]或生物支架(SIS;小肠黏膜下层)上,以在狒狒膀胱扩大模型中再生膀胱组织。我们着手确定用上述接种干细胞的支架进行再生的膀胱组织以及接受BAE的狒狒的蛋白质表达谱。数据表明,植入POCO和SIS的动物在天然组织和再生组织之间具有高度的蛋白质同质性,而BAE动物在长期植入后的组织之间显示出异质性蛋白质表达。我们认为,接种干细胞的支架可以在蛋白质水平上重现与天然组织几乎无法区分的组织,并且可以替代诸如BAE之类的手术。