Increased urethral resistance by periurethral injection of low serum cultured adipose‐derived mesenchymal stromal cells in rats

Abstract

Objectives:To evaluate the effects of a periurethral injection of low serum cultured adipose tissue-derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence. Methods: F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4 weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats. Results: At 2 weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4 weeks, the increase in LPP in the LASC group remained , whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4 weeks, most of the LASC were positive for myogenic antigens including a-smooth muscle actin, desmin and calponin I. Conclusions: Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.

Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells

“…Preliminary results demonstrated possible improvement of urine linkage in patients with SUI [52, 53], and we also confirmed myogenic differentiation of ADSC by periuretral injection in an SUI rat model [54]. In the present study, treatment of ADSC with exogenous FABP4, but not FABP5, was partially associated with myogenesis.…”

The Effect of Endoscopic Administration of Autologous Porcine Muscle-derived Cells Into the Urethral Sphincter

“…Previously, the functional evaluation was usually performed after the transplantation to the directly injured 9,14,15,25 or denervated urethra. 7 In the majority of these studies, the significant improvement of urethral closure in transplanted animals was noted when compared to the injured nontransplanted groups. [4][5][6]12,13,15 The reason for the inconsistency of results is probably the lack of fresh urethra injury in the presented study.…”

“…In the last decade, numerous studies have been performed in order to test the procedure of cellular transplantations into the urethral sphincter. It was shown that different cell types, such as myoblasts, 4 muscle derived stem cells, 5 bone marrow, or adipose tissue-derived mesenchymal stem cells 6,7 can survive after the injection into the urethral wall. However, although numerous different studies were performed to examine the procedure of intraurethral cell transfer, the graft has never been administered with the use of an endoscope in animal models.…”

“…However, although numerous different studies were performed to examine the procedure of intraurethral cell transfer, the graft has never been administered with the use of an endoscope in animal models. In previously published studies, the cell transplantations were performed after exposing the urethra during laparotomy [5][6][7][8][9][10][11][12][13][14] even in large animal models. 15 However, injection during laparotomy is rather an unacceptable method in cases of human patients as the low invasiveness is claimed to be an important advantage of cellular therapy for urinary incontinence.…”

Potential application of adipose tissue-derived stem cells for urological Disease

“…Implanted ADSCs were supposed to differentiate into skeletal muscle, smooth muscle, nerve, and endothelial cells according to their immunohistochemical analyses. Watanabe et al [70] and Wu et al [71] conducted similar experiments in a pelvic nerve injury-induced SUI model. According to their data, animals with ADSC treatment also showed significant myogenic differentiation or regeneration and improved LPP results.…”