The effects of bone marrow stem and progenitor cell seeding on urinary bladder tissue regeneration

Abstract

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/mm2)]. 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.

A biodegradable microgrooved and tissue mechanocompatible citrate-based scaffold improves bladder tissue regeneration

“…As anticipated, augmentations with cell-seeded scaffolds in this study showed a significant increase in revascularization and nerve regeneration compared to that of the cell-free scaffolds, and the extent of vascular and nerve regeneration is analogous to previous publications. 22,29 Furthermore, the presence of microgrooves appeared to induce ingrowth of nerves in the unseeded Microgrooved group. Approximately 60% of the smooth group had observed nerve regeneration compared to about 90% of the Microgrooved group.…”

The Role of MSCs and Cell Fusion in Tissue Regeneration

“…In a rat urinary bladder augmentation model, MSCs and hematopoietic stem/progenitor cells were seeded onto different scaffolds and were transplanted into rats. This treatment promoted bladder tissue regeneration, partially through the formation of blood vessels [88]. The application of an ointment based on MSC's secretome had an accelerating effect on skin wound healing in mice [89].…”

Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods

“…Drew et al observed neovascularization in the presence of exogenous Vascular Endothelial Growth Factor (VEGF) ( Dew et al, 2016 ). However, another study revealed that in bladder tissue regeneration, poly (octamethylene citrate) (POC) composites outperformed small intestinal submucosa (SIS) scaffolds in tissue vascularization, while POC scaffolds lack any exogenous growth factor ( Bury et al, 2021 ). Stem cells are considered beneficial in angiogenesis induction, as they can differentiate into endothelial cells or secrete various growth factors.…”