Histological and Urodynamic Effects of Autologous Stromal Vascular Fraction Extracted from Fat Tissue with Minimal Ex Vivo Manipulation in a Porcine Model of Intrinsic Sphincter Deficiency

Boissier, Romain; Magalon, Jérémy; Sabatier, Florence; Véran, Julie; Guy, Laurent; Giusiano, Sophie; García, Stéphane; Dignat-George, Françoise; Arnaud, Laurent; Magalon, G.; Lechevallier, É.; Berdah, Stéphane; Karsenty, G.

doi:10.1016/j.juro.2016.04.099

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…A recent large animal study confirmed that the SVF is a safe and effective treatment for SUI [20] . SVF contains substantial number of adipose derived stromal/stem cells (ADSCs) as well as leukocytes and endothelial cells [2] .…”

Section: Discussionmentioning

confidence: 90%

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

Inoue

Kishimoto

Kaga

et al. 2018

Regenerative Therapy

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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.

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Section: Discussionmentioning

confidence: 90%

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

Inoue

Kishimoto

Kaga

et al. 2018

Regenerative Therapy

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“…Adipose‐derived stromal vascular fraction (SVF) is a rich source of AdMSCs . Studies have reported that administration of uncultured SVF could attenuate injury and improve the function of various tissues and organs, such as the heart , kidney , urethral sphincter , etc. Recently, both our team and other groups have demonstrated that, compared with AdMSCs, uncultured SVF exhibited equal effect on attenuating acute renal I/R injury and recovering penile erection .…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Uncultured Adipose-Derived Stromal Vascular Fraction on Testicular Injury Induced by Torsion-Detorsion in Rats

Zhou

Song

et al. 2018

Stem Cells Translational Medicine

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Torsion‐detorsion (T/D)‐induced testicular injury may lead to male subfertility and even infertility. Stem cell therapy provides an alternative to attenuate testicular injury and promote spermatogenesis. Adipose‐derived stromal vascular fraction (SVF) can be acquired conveniently without in vitro expansion, which may avoid the potential risks of microbial contamination, xenogenic nutritional sources, etc., during cell culture. In this study, we investigate the protective effects of autologous uncultured SVF on testicular injury and spermatogenesis in a rat model of T/D. Animals were randomly divided into sham, T/D+ phosphate‐buffered saline, and T/D + SVF groups (18 rats in each group). SVF was isolated, labeled with lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine, and transplanted into T/D testis by local injection. At 3, 7, 14, and 28 days F surgery, testicular tissue and serum samples were harvested for histopathological, immunohistochemical, Western blot, and enzyme‐linked immunosorbent assays. Histopathological findings demonstrated severe injury in the testis with decreased Johnsen's score led by T/D, while uncultured SVF reduced testicular injury and elevated the decreased score. Injected SVF cells were mainly integrated into interstitial region and seminiferous tubules, enhanced the secretion of basic fibroblast growth factor and stem cell factor in the testis, contributed to the declining level of malondialdehyde and restoration of hormonal homeostasis, and then reduced the injury of Leydig cells and germ cells, as well as promoting spermatogenesis. Our findings demonstrated that autologous uncultured SVF could protect the testis from testicular ischemia‐reperfusion injury and promote spermatogenesis, which provide significant clinical implications for the prevention of infertility induced by testicular T/D. Stem Cells Translational Medicine 2019;8:383–391

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“…Boissier et al evaluated the healing abilities of autologous stromal vascular fraction prepared from adipose tissue in a porcine model of intrinsic sphincter deficiency. In this study, stromal vascular fraction injection was associated with a reduction of the urethral injury surface and increased maximum urethral pressure when compared to the respective controls …”

Section: Methodsmentioning

confidence: 62%

“…ADSCs have been tested in preclinical studies in murine, rabbits, and porcine SUI models. Silwal Gautam et al demonstrated that the implantation of ADSCs into cryoinjured female rabbit urethras promoted the recovery of urethral function by myogenic differentiation as well as neuroregeneration.…”

Section: Methodsmentioning

confidence: 99%

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Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients

Zambon

Williams

Bennington

et al. 2019

Neurourology and Urodynamics

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Stress urinary incontinence (SUI) is an age health‐related issue that generates interest due to its considerable public health burden and the controversies surrounding treatment. It is highly prevalent affecting 30–40% of all women during their lifetime. Midurethral slings are the standard of gold standard treatment for female patients with SUI. They have excellent short‐term cure rates; however, their efficacy tends to decrease over time and patients often report urinary incontinence recurrence. This paper addresses the applicability of regenerative medicine and tissue engineering for the treatment of SUI in female patients. Cell‐based treatment with periurethral injection of autologous adipose or muscle‐derived stem cells have been used for SUI; however, the cure rates and SUI recurrence at 1 year were 40% and 70%, respectively. Novel minimally invasive approaches, such as low‐intensity extracorporeal shock wave therapies have shown promising results in SUI animal models. In addition, local injection of growth factors, chemokines, and specific antibodies have shown histological evidence of neoangiogenesis, nerve, and sphincter regeneration in rodents and nonhuman primates with SUI. The use of bioactive factors and proteins secreted by cells, which is called secretomes, have been recognized as key regulators of various mechanisms, such as immunomodulation, angiogenesis, inflammation, apoptosis, and tissue repair. Emerging therapies aiming to replace or restore tissues and organ functionality may improve the long‐term efficacy and in the near future may represent the standard of care for the treatment of SUI.

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Histological and Urodynamic Effects of Autologous Stromal Vascular Fraction Extracted from Fat Tissue with Minimal Ex Vivo Manipulation in a Porcine Model of Intrinsic Sphincter Deficiency

Abstract: These data demonstrate the ability of an autologous stromal vascular fraction to improve the urethral healing process in a large animal model of intrinsic sphincteric deficiency.

Cited by 9 publications

References 32 publications

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

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

Protective Effects of Uncultured Adipose-Derived Stromal Vascular Fraction on Testicular Injury Induced by Torsion-Detorsion in Rats

Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients

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