Division of Pediatric Urology, Ann & Robert H. Lurie Children's Hospital, 155 East Chicago Ave., Chicago, IL, 60611, USA.
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.
Sci Rep. 2021 Jan 27;11(1):2322. doi: 10.1038/s41598-021-81939-5.
Complications associated with urinary bladder augmentation provide the motivation to delineate alternative bladder tissue regenerative engineering strategies. We describe the results of varying the proportion of bone marrow (BM) mesenchymal stem cells (MSCs) to CD34 + hematopoietic stem/progenitor cells (HSPCs) co-seeded onto synthetic POC [poly(1,8 octamethylene citrate)] or small intestinal submucosa (SIS) scaffolds and their contribution to bladder tissue regeneration. Human BM MSCs and CD34 + HSPCs were co-seeded onto POC or SIS scaffolds at cell ratios of 50 K CD34 + HSPCs/15 K MSCs (CD34-50/MSC15); 50 K CD34 + HSPCs/30 K MSCs (CD34-50/MSC30); 100 K CD34 + HSPCs/15 K MSCs (CD34-100/MSC15); and 100 K CD34 + HSPCs/30 K MSCs (CD34-100/MSC30), in male (M/POC; M/SIS; n = 6/cell seeded scaffold) and female (F/POC; F/SIS; n = 6/cell seeded scaffold) nude rats (n = 96 total animals). Explanted scaffold/composite augmented bladder tissue underwent quantitative morphometrics following histological staining taking into account the presence (S+) or absence (S-) of bladder stones. Urodynamic studies were also performed. Regarding regenerated tissue vascularization, an upward shift was detected for some higher seeded density groups including the CD34-100/MSC30 groups [F/POC S- CD34-100/MSC30 230.5 ± 12.4; F/POC S+ CD34-100/MSC30 245.6 ± 23.4; F/SIS S+ CD34-100/MSC30 278.1; F/SIS S- CD34-100/MSC30 187.4 ± 8.1; (vessels/mm)]. Similarly, a potential trend toward increased levels of percent muscle (≥ 45% muscle) with higher seeding densities was observed for F/POC S- [CD34-50/MSC30 48.8 ± 2.2; CD34-100/MSC15 53.9 ± 2.8; CD34-100/MSC30 50.7 ± 1.7] and for F/SIS S- [CD34-100/MSC15 47.1 ± 1.6; CD34-100/MSC30 51.2 ± 2.3]. As a potential trend, higher MSC/CD34 + HSPCs cell seeding densities generally tended to increase levels of tissue vascularization and aided with bladder muscle growth. Data suggest that increasing cell seeding density has the potential to enhance bladder tissue regeneration in our model.
与膀胱扩大相关的并发症为描绘替代膀胱组织再生工程策略提供了动力。我们描述了改变骨髓（BM）间充质干细胞（MSCs）与 CD34+造血干细胞/祖细胞（HSPCs）在合成 POC[聚（1,8 辛二羧酸）]或小肠黏膜下层（SIS）支架上共接种的比例对膀胱组织再生的影响。将人 BM MSCs 和 CD34+HSPCs 以 50K CD34+HSPCs/15K MSCs（CD34-50/MSC15）；50K CD34+HSPCs/30K MSCs（CD34-50/MSC30）；100K CD34+HSPCs/15K MSCs（CD34-100/MSC15）；和 100K CD34+HSPCs/30K MSCs（CD34-100/MSC30）的细胞比在雄性（M/POC；M/SIS；n=6/接种细胞的支架）和雌性（F/POC；F/SIS；n=6/接种细胞的支架）裸鼠（共 96 只动物）中进行共接种。在考虑有无膀胱结石的情况下，对植入支架/复合增强膀胱组织进行组织学染色后的定量形态计量学分析。还进行了尿动力学研究。关于再生组织的血管化，一些较高接种密度组（包括 CD34-100/MSC30 组）检测到向上移位[F/POC S-CD34-100/MSC30 230.5±12.4；F/POC S+CD34-100/MSC30 245.6±23.4；F/SIS S+CD34-100/MSC30 278.1；F/SIS S-CD34-100/MSC30 187.4±8.1；（血管/mm）]。同样，对于 F/POC S-，观察到较高的接种密度与更高水平的肌肉（≥45%肌肉）百分比之间存在潜在的趋势[CD34-50/MSC30 48.8±2.2；CD34-100/MSC15 53.9±2.8；CD34-100/MSC30 50.7±1.7]，对于 F/SIS S-，观察到类似的趋势[CD34-100/MSC15 47.1±1.6；CD34-100/MSC30 51.2±2.3]。作为一种潜在的趋势，较高的 MSC/CD34+HSPCs 细胞接种密度通常倾向于增加组织血管化水平并有助于膀胱肌肉生长。数据表明，增加细胞接种密度有可能增强我们模型中的膀胱组织再生。
