Understanding the role of mesenchymal stem cells in urinary bladder regeneration—a preclinical study on a porcine model

Abstract

BackgroundThe tissue engineering of urinary bladder advances rapidly reflecting clinical need for a new kind of therapeutic solution for patients requiring urinary bladder replacement. Majority of the bladder augmentation studies have been performed in small rodent or rabbit models. Insufficient number of studies examining regenerative capacity of tissue-engineered graft in urinary bladder augmentation in a large animal model does not allow for successful translation of this technology to the clinical setting. The aim of this study was to evaluate the role of adipose-derived stem cells (ADSCs) in regeneration of clinically significant urinary bladder wall defect in a large animal model.MethodsADSCs isolated from a superficial abdominal Camper’s fascia were labeled with PKH-26 tracking dye and subsequently seeded into bladder acellular matrix (BAM) grafts. Pigs underwent hemicystectomy followed by augmentation cystoplasty with BAM only (n = 10) or BAM seeded with autologous ADSCs (n = 10). Reconstructed bladders were subjected to macroscopic, histological, immunofluoresence, molecular, and radiological evaluations at 3 months post-augmentation.ResultsSixteen animals (n = 8 for each group) survived the 3-month follow-up without serious complications. Tissue-engineered bladder function was normal without any signs of post-voiding urine residual in bladders and in the upper urinary tracts. ADSCs enhanced regeneration of tissue-engineered urinary bladder but the process was incomplete in the central graft region. Only a small percentage of implanted ADSCs survived and differentiated into smooth muscle and endothelial cells.ConclusionsThe data demonstrate that ADSCs support regeneration of large defects of the urinary bladder wall but the process is incomplete in the central graft region. Stem cells enhance urinary bladder regeneration indirectly through paracrine effect.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1070-3) contains supplementary material, which is available to authorized users.

Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model

“…Meanwhile, MSCs may stay undifferentiated and release growth factors, which act as a feeder layer rich in trophic factors that trigger the migration of native cells from the surrounding tissues. At this point, a recent study concerning bladder tissue regeneration revealed that differentiation plays a minor role in the final regeneration effect mediated by MSCs [13]. Furthermore, BMSCs are commonly used in differentiating into SMCs and urothelium in the case of bladder tissue regeneration [35].…”

“…As two main autologous MSC types, adipose-derived mesenchymal stem cells (ADSCs), and bone marrow-derived mesenchymal stem cells (BMSCs) are generally applied in tissue regeneration investigations due to their abundance and easy access. And some previous studies have found that the source of MSCs (bone marrow vs adipose tissue) has no impact on the regeneration of tissue-engineered urinary bladder [13]. According to recent literatures, BMSCs have been proved to undergo directed differentiation toward endodermal derived urothelium and develop into mature bladder tissue in the appropriate signaling environment [14].…”

Mesenchymal stromal cells modulate the molecular pattern of healing process in tissue-engineered urinary bladder: the microarray data

“…The self-regenerating capability is not however enough to rebuild the primary bladder wall structure. Therefore, boosting endogenous regenerative potency is necessary [5]. Stem cells stimulate regeneration of tissue-engineered urinary bladder but the molecular basis of this process remains unknown until now.…”

“…Principles of bladder tissue engineering have been established a decade after the landmark research by Atala et al, which drew the urology community’s attention on opportunities offered by regenerative medicine [3]. Stem cells, especially mesenchymal stem cells (MSCs), are the most commonly used cell population in tissue engineering, which can deliver paracrine factors that rearrange the local healing response [4, 5]. Numerous studies indicated that stem cells promote regeneration of tissue-engineered urinary bladder preventing fibrosis and scar formation [4–12].…”

Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: Inspiring a new Kind of Medicine

“…Both cell-derived and tissue/organ-derived ECMs have been used is several studies and have shown the capability to direct cellular behavior ( Table 2). Cartilage Extracellular matrix Chondrogenic differentiation [133,134] Bladder Extracellular matrix Promotion of cellular proliferation and stemness [135,136] A fibroblast-derived extracellular matrix (fd-ECM) was able to induce chondrogenic differentiation of adipose-derived mesenchymal stromal cells (ad-MSCs) in vitro [91]. Although the Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 21 August 2019 doi:10.20944/preprints201908.0222.v1…”