Aerosol transfer of bladder urothelial and smooth muscle cells onto demucosalized colonic segments for bladder augmentation: In vivo, long term, and functional pilot study

Abstract

Summary Background Bladder augmentation technique has changed over the years and the current practice has significant adverse health effects and long-term sequelae. Previously, we reported a novel cell transfer technology for covering demucosalized colonic segments with bladder urothelium and smooth muscle cells through an aerosol spraying of these cells and a fibrin glue mixture. Objective To determine the long-term durability and functional characteristics of demucosalized segments of colon repopulated with urothelial cells in the bladder of swine for use in augmentation cystoplasty. Study design Nine swine were divided into three groups. The first group (control) underwent standard colocystoplasty; the second group underwent colocystoplasty with colonic demucosalization and aerosol application of fibrin glue and urothelial cell mixture; in the third group detrusor cells were added to the mixture described in group two. The animals were kept for 6 months. Absorptive and secretory function was assessed. Bladders were harvested for histological and immunohistochemical evaluation. Results All animals but one in the experimental groups showed confluent urothelial coverage of the colonic segment in the bladder without any evidence of fibrosis, inflammation, or regrowth of colonic epithelial cells. Ten percent of the instilled water in the bladder was absorbed within an hour in the control group, but none in experimental groups(p=0.02). The total urine sediment and protein contents were higher in the control group compared with experimental groups (p<0.05). Discussion Both study groups developed a uniform urothelial lining. Histologically, the group with smooth muscle had an added layer of submucosal smooth muscle. Six months after bladder augmentation the new lining was durable. We were also able to demonstrate that the reconstituted augmented segments secrete and absorb significantly less than the control colocystoplasty group. We used a non-validated simple method to evaluate permeability of the new urothelial lining to water. To determine if the aerosol transfer of bladder cells would have behaved differently in the neurogenic bladder population, this experiment should have been performed in animals with neuropathic bladders. Conclusion Aerosol spraying of single cell suspension of urothelial and muscular cells with fibrin glue resulted in coverage of the demucosalized intestinal segment with a uniform urothelial layer. This new lining segment was durable without regrowth of colonic mucosa after 6 months. The new reconstituted segment absorbs and secretes significantly less than control colocystoplasty.

Smooth Muscle Precursor Cells Derived from Human Pluripotent Stem Cells for Treatment of Stress Urinary Incontinence

“…Bladder SMCs as a source of SMCs for bladder tissue regeneration has been studied [38][39][40][41]. The bladder SMCs and urothelial cells were reported to contribute to the development of bladder smooth muscle [42].…”

Auto Micro Atomization Delivery of Human Epidermal Organoids Improves Therapeutic Effects for Skin Wound Healing

“…Cell spraying, by means of aerosolization of cell suspensions in air, has been used previously to spray keratinocytes on skin wounds to accelerate healing (Kirsner et al, 2012;Esteban-Vives et al, 2016b), melanocytes to restore skin color (Iman et al, 2013), and bladder urothelial and smooth muscle cells to reconstitute segments of colon used in bladder augmentation (Hidas et al, 2015). However, there is an urgent need to develop improved methods of spraying considering large and irregular wounds and cutaneous injuries.…”

Cystoplasty Combined Autologous Peritoneum with Ileal Seromuscular segment: a new model study

“…The reasons are as follows: rstly, sigmoid colon is closer to anus than ileum; secondly, the lumen of sigmoid colon is bigger than that of ileum; thirdly, the ileal well is thinner than that of sigmoid colon. Hafez et al [9] also used this distending technique, but under the help of hydrodistension. They had the colonic segment lled with water, hence striping the seromuscular ap.…”