Bladder regeneration through stem cell therapy

ABSTRACT

Introduction: Impaired bladder function in children and adults often causes lifelong morbidity, as functional therapeutic approaches in this field are nonexistent. If reconstructive procedures are required, intestinal tissue is used as a gold standard for bladder repair. As this procedure is associated with significant long-term complications there is a strong clinical need for alternative sources of stable and reliable bladder tissue, of which stem cells are considered most promising.

Areas covered: This review focusses on the recent development in stem cell use for bladder bioengineering. Further, we discuss the importance of the microenvironment in stem cell differentiation, function and tissue regeneration and its effect on the development of functional bladder tissue.

Expert opinion: Functional bladder bioengineering requires a complex approach that involves the development of a multi-layered scaffold, with each layer offering a specific microenvironment for the generation and support of the respective cell type used in its redevelopment. The formation of cellular cross-talk within and between the layers is the key in this process. While autologous stem cells may provide a viable source of tissue for bladder reconstruction, their in situ activation combined with repair of the diseased microenvironment may offer better, more lasting solutions for functional bladder regeneration.

KEYWORDS:

• Bladder
• stem cells
• tissue engineering
• regenerative medicine
• microenvironment

Article Highlights

• Multilayered natural and hybrid scaffolds are ideally suited for bladder wall bioengineering, as they offer the benefits of multiple microenvironments representing the respective bladder compartments.

• Adult autologous MSC, ADSC, and USC represent the most viable source for the generation of clinically applicable bladder tissue, mainly due to their high abundance, ease of isolation, and potent immunomodulatory, pro-angiogenic, and neuroregenerative properties.

• High numbers of urothelium-like cells can be generated from almost all stem cell types using urothelial cell-conditioned culture media, with the best results obtained when cells of urothelial origin are being used as a source.

• ADSC and MSC are ideal cells to generate high numbers of phenotypically stable, functional SMCs via direct co-culture, using conditional media or by induction with TGF-β1 and BMP4 or heparin.

• Fast and stable vascularization of the transplanted graft may be achieved using a combination of endothelial progenitor cells to form a vascular network in the scaffold prior to implantation, oxygen-releasing biomaterials, and tightly regulated pro-angiogenic growth factor presentation.

• The use of NGF and other signaling cues, in combination with conductive electrospun biomaterials and stem cell-based Schwann-like cells, may help to promote stable bladder reinnervation during regeneration.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper has been funded by the Erich Fromm Research Fellowship and the Helmut Horten Foundation.