Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34 + hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34 + grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.
Animal models that have been used to examine the regenerative capacity of cell-seeded scaffolds in a urinary bladder augmentation model have ultimately translated poorly in the clinical setting. This may be due to a number of factors including cell types used for regeneration and anatomical/ physiological differences between lower primate species and their human counterparts. We postulated that mesenchymal stem cells (MSCs) could provide a cell source for partial bladder regeneration in a newly described nonhuman primate bladder (baboon) augmentation model. Cell-sorted2 baboon MSCs transduced with green fluorescent protein (GFP) were seeded onto small intestinal submucosa (SIS) scaffolds. Baboons underwent an approximate 40%-50% cystectomy followed by augmentation cystoplasty with the aforementioned scaffolds or controls and finally enveloped with omentum. Bladders from sham, unseeded SIS, and MSC/SIS scaffolds were subjected to trichrome, H&E, and immunofluorescent staining 10 weeks postaugmentation. Immunofluorescence staining for muscle markers combined with an anti-GFP antibody revealed that >90% of the cells were GFP Disclosure of potential conflicts of interest is found at the end of this article.
We present an overview of current and emerging lasers for Urology. We begin with an overview of the Holmium:YAG laser. The Ho:YAG laser is the gold standard lithotripsy modality for endoscopic lithotripsy, and compares favorably to standard electrocautery transurethral resection of the prostate for benign prostatic hyperplasia (BPH). Available laser technologies currently being studied include the frequency doubled double-pulse Nd:Yag (FREDDY) and high-powered potassium-titanyl-phosphate (KTP) lasers. The FREDDY laser presents an affordable and safe option for intracorporeal lithotripsy, but it does not fragment all stone compositions, and does not have soft tissue applications. The high power KTP laser shows promise in the ablative treatment of BPH. Initial experiments with the Erbium:YAG laser show it has improved efficiency of lithotripsy and more precise ablative and incisional properties compared to Ho:YAG, but the lack of adequate optical fibers limits its use in Urology. Thulium:YAG fiber lasers have also demonstrated tissue ablative and incision properties comparable to Ho:YAG. Lastly, compact size, portability, and low maintenance schedules of fiber lasers may allow them to shape the way lasers are used by urologists in the future.
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