Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma

Abstract

IntroductionAutologous transplantation of adipose stromal vascular fraction (SVF) is a cost-effective and technically accessible option for cell therapy. Clinical study of SVF transplantation for male stress urinary incontinence (SUI) is underway, but the effectiveness remains unknown for female SUI, majority of which is caused by childbirth trauma.MethodsVaginal Distension (VD) rats were generated as in vivo model for female SUI. To quantitate the severity of SUI, leak point pressure (LPP) was measured by placing a bladder catheter. There was a characteristic waveform of LPP with two-peaks, and we counted the second peak as an LPP value. Adipose SVF was separated from inguinal fat and delivered into external urethral sphincter (EUS) through transperineal injection. LPP was measured 7 or 14 days after SVF transplantation. Tissue damage and collagen synthesis around the EUS were visualized by Masson's trichrome and eosin staining. Antibody against α-smooth muscle actin (α-SMA) was used to stain smooth muscle or activated stromal cells. Donor SVF cells were distinguished from recipient EUS tissue by tracking with GFP transgene.ResultsVD procedure decreased the frequency at which the normal LPP waveform appeared and lowered the LPP value. SVF injection normalized the waveform as well as the level of LPP. VD disrupted histological structure of EUS and SVF failed to differentiate into striatal muscles. Instead, SVF increased α-SMA positive cells and collagen synthesis but the phenomena depended on VD stimulus. GFP tracking indicated that the transplanted SVF cells persisted for four weeks and synthesized α-SMA protein simultaneously.ConclusionsAutologous transplantation of adipose SVF displayed bulking effects through collagen synthesis. However, such heterotopic activation was dependent on tissue damage.

Treatment of male stress urinary incontinence using autologous adipose‐derived regenerative cells: Long‐term efficacy and safety

“…ADRCs isolated with the Celution system were composed of a heterogeneous cell population including adipose stem cells, and were also reported to show pluripotency and secretion of cytokines . Based on preclinical experimental injection of adipose stem cells or ADRCs into the rat urethra, it was suggested that the mechanisms involved in the improvement of sphincter function included a bulking effect, regeneration of smooth muscle and increased blood flow caused by adipose stem cells or ADRC injection, as also confirmed by our previous clinical study . We are carrying out further analysis of cell characteristics using human ADRCs isolated with the Celution system.…”

Regenerative treatment for male stress urinary incontinence by periurethral injection of adipose‐derived regenerative cells: Outcome of the ADRESU study

“…The previous basic and exploratory clinical study suggested that the mechanisms of action of this treatment are differentiation of the injected cells to smooth muscle cells, an increase in blood flow caused by an increase in vascularization as a result of cytokine production by the injected cells and maintenance of the bulking effect by the injected adipose tissue combined with ADRCs 17,18 . Inoue et al also reported that injection of uncultured autologous stromal vascular fractions to the external urethral sphincter improves the urethral sphincteric function, and increases anti‐smooth muscle antibody positive cells and collagen synthesis in a rat SUI model 22 . This hypothesis was partly confirmed in the secondary outcomes of this study; evaluation of blood flow by the transrectal enhanced ultrasonography in this study showed the progressive increase of blood flow at the injection site, MUCP increased and also magnetic resonance imaging analysis showed the injected adipose tissue around the urethra was maintained with minimal absorption at 52 weeks.…”

The Effect of Mesenchymal Stem Cells, Adipose Tissue Derived Stem Cells, and Cellular Stromal Vascular Fraction on the Repair of Acute Anal Sphincter Injury in Rats

“…Compared to ADSC, the preparation of SVF is even simpler, with single protease digestion yielding 2–6 × 10 6 SVF cells (CSVF) per 1 mL of fat with ≥90% cell viability. Many studies have shown that ADSC and CSVF can promote tissue repairs, such as skeletal tissue [ 28 , 29 , 30 , 31 ], muscle tissue [ 32 , 33 , 34 ], nerve damage [ 35 , 36 , 37 , 38 ], and cardiovascular injury [ 39 , 40 , 41 ]. Meanwhile, the tissue source of ADSC and CSVF is widely available, and a large amount of adipose tissue can be obtained for ADSC and CSVF extraction during liposuction, manual liposuction, etc., while the invasive procedure in obtaining bone marrow MSC and muscle-derived stem cells have limited their application in clinic.…”