RETRACTED ARTICLE: Transurethral ultrasonography-guided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence

In the last years preclinical studies have paved the way for the use of adult muscle derived stem cells for reconstruction of the lower urinary tract. Between September 2002 and October 2004, 42 women and 21 men suffering from urinary stress incontinence (age 36–84 years) were recruited and subsequently treated with transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. In parallel, 7 men and 21 women (age 39–83 years) also diagnosed with urinary stress incontinence were treated with standard transurethral endoscopic injections of collagen. Patients were randomly assigned to both groups. After a follow-up of 12 months incontinence was cured in 39 women and 11 men after injection of autologous myoblasts and fibroblasts. Mean quality of life score (51.38 preoperatively, 104.06 postoperatively), thickness of urethra and rhabdosphincter (2.103 mm preoperatively, 3.303 mm postoperatively) as well as contractility of the rhabdosphincter (0.56 mm preoperatively, 1.462 mm postoperatively) were improved postoperatively. Only in two patients treated with injections of collagen incontinence was cured. The present clinical results demonstrate that, in contrast to injections of collagen, urinary incontinence can be treated effectively with ultrasonography-guided injections of autologous myo- and fibroblasts.     

Adult stem cell therapy of female stress urinary incontinence

OBJECTIVES: To investigate the efficacy of transurethral ultrasound (TUUS)-guided injections of autologous myoblasts and fibroblasts in women with incontinence. METHODS: Between January and June 2005, 20 female patients suffering from stress urinary incontinence (SUI) were included. Skeletal muscle biopsies were taken from the left arm to obtain cultures from autologous fibroblasts and myoblasts. By TUUS guidance the fibroblasts were injected into the urethral submucosa and the myoblasts were injected into the rhabdosphincter. A defined incontinence score, quality-of-life score and urodynamic, electromyographic, and laboratory parameters, as well as morphology and function of urethra and rhabdosphincter were evaluated before and up to 2 yr after therapy. RESULTS: Eighteen of 20 patients were cured 1 yr after injection of autologous stem cells and in 2 patients SUI was improved. Two years after therapy 16 of the 18 patients presented as cured, 2 others were improved, and 2 were lost to follow-up. Incontinence and quality-of-life scores were significantly improved postoperatively. The thickness of urethra and rhabdosphincter as well as activity and contractility of the rhabdosphincter were also statistically significantly increased after therapy. CONCLUSIONS: Clinical results demonstrate that SUI can be treated effectively with autologous stem cells. The present data support the conclusion that this therapeutic concept represents an elegant and minimally invasive treatment modality to treat SUI.     

Autologous myoblasts and fibroblasts for female stress incontinence: a 1-year follow-up in 123 patients

OBJECTIVE: To assess the efficacy and safety of the application of autologous myoblasts and fibroblasts for treating female stress urinary incontinence (SUI) after a follow-up of >/=1 year. PATIENTS AND METHODS: In all, 123 women with SUI (aged 36-84 years) were treated with transurethral ultrasonography-guided injections with autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were suspended in a small amount of collagen as carrier material and injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. All patients were evaluated before and 12 months after the injection using the Incontinence and Quality of Life Instrument (I-QOL) scores, urodynamic variables, and morphology and function of the urethra and rhabdosphincter. RESULTS: At 1 year after implanting the cells, 94 of the 119 women (79%) were completely continent, 16 (13%) had a substantial improvement and nine (8%) a slight improvement. Four patients were lost to follow-up.The incontinence and I-QOL scores, and the thickness, contractility and electromyographic activity of the rhabdosphincter were significantly improved after treatment. CONCLUSIONS: These results show the efficacy and safety of transferring autologous myoblasts and fibroblasts in the treatment of female SUI, after a follow-up of 1 year.     

Células madre derivadas de músculo para la incontinencia urinaria de esfuerzo

The knowledge of the urinary effort incontinence (UEI) has increased, giving like result an ample range of different therapeutic options available. The middle urethra and external urethral sphincter are the focus in management of UEI. Stem cells therapy for the regenerative repair of the deficient sphincter has been the leading research of incontinence. Obtaining autologous myoblasts and fibroblasts of skeletal muscle-biopsies, cultivating them and transplanting them after its differentiation, into the external urethral sphincter it warns a new concept in the treatment of the incontinence. Instead of using heterologous materials such as synthetic mesh (slings) or bulking agents (collagen, silicone, etc); we now have the potential to restore function with the use of autologous stem cells.     

Persistence and survival of autologous muscle derived cells versus bovine collagen as potential treatment of stress urinary incontinence

PURPOSE: We explored the use of autologous muscle derived cells as a method of treating stress urinary incontinence. We determined whether urethral muscle derived cell injection is feasible and compared it with bovine collagen injection. MATERIALS AND METHODS: Muscle derived cells isolated from female Sprague-Dawley rats were first transduced with retrovirus carrying the transgene for beta-galactosidase. We injected approximately 1 to 1.5 x 106 cells into the bladder wall and proximal urethra of 6 autologous animals. Tissue was harvested after 3 and 30 days, sectioned, stained for fast myosin heavy chain and assayed for beta-galactosidase. To compare muscle derived cell and bovine collagen injections 100 microl. of commercially available bovine collagen were also injected in Sprague-Dawley female rats. Tissue was harvested in 3 animals each after 3 and 30 days, sectioned and stained for trichrome. Subsequently, 3 adult SCID mice were used to compare the level of transgene expression at each time point after injecting 1.5 x 106 cells per injection, which were transduced with adenovirus carrying the transgene for beta-galactosidase. RESULTS: A large number of cells expressing beta-galactosidase were observed in the bladder and urethral wall 3 and 30 days after autologous cell injection in Sprague-Dawley rats. The persistence of primary muscle derived cells at 3 days was similar to that of collagen. However, at 30 days there was significant cell persistence while only a minimal amount of injected bovine collagen was detectable. Approximately 88% of the beta-galactosidase expression at day 3 remained at day 30 in SCID mice. CONCLUSIONS: We present 2 new findings important for the emerging field of urological tissue engineering, including the feasibility of injecting autologous skeletal muscle derived cells into the lower urinary tract and the greater persistence of such injected cells versus injected bovine collagen. Therefore, autologous muscle derived cell injection may be an attractive alternative treatment option for stress urinary incontinence.     

Functional and histological changes after myoblast injections in the porcine rhabdosphincter

OBJECTIVE: Transurethral ultrasound-guided injection of autologous myoblasts has recently been shown to cure urinary stress incontinence. In the present study, the dose-dependent changes in maximal urethral closure pressures after application of myoblasts were investigated in a porcine animal model. METHODS: Myoblast cultures were grown from a porcine muscle biopsy. The biopsy was enzymatically dissociated by using a modified cell dispersion technique. Single myoblasts in suspension were manually collected with a micropipette under microscopic control. Next a clonal myoblast culture was prepared. Before the cells were applied, fluorescence labelling (PKH) was used to assess integration of the injected myoblasts into the rhabdosphincter. With the help of a transurethral ultrasound probe (23 F, 11 MHz) and a special injection system, the myoblasts were injected into the rhabdosphincter of five pigs under direct sonographic control. Into two different areas of the rhabdosphincter, increasing different cell counts were injected (total volume 1.5 ml). At each area, 10 depots of 150 microl volume were injected all along the rhabdosphincter. The following cell counts were used: 1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6) (low range) 5.69 x 10(6), 8.1 x 10(6), 1.13 x 10(7), 1.6 x 10(7) (mid range) 2.26 x 10(7), 4.4 x 10(7), and 7.8 x 10(7) (high range). To avoid possible cell rejection, we immunosuppressed the pigs with daily cortisone (1g Solu Dacortin) because allogenic myoblasts were used. Urethral pressure profiles (UPPs) were measured before and 3 wk postoperatively before the pigs were put to sleep. The lower urinary tract was removed in all pigs for histological analysis. RESULTS: Histological examination of the specimens revealed that the injected cells had survived at the injection site and had formed new myofibres. Overall the UPP curves revealed dose-dependent changes. Statistically significant increased pressure values of up to more than 300% could be observed in all cases in which higher concentrations of cells had been applied. Increases were also noted in mid range concentrations although not to such a high extent (approximately 150%). Pressure values had even diminished (approximately 50%) after injecting the three lowest concentrations (1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6)). CONCLUSIONS: The present results show that the effects after application of myoblasts into the rhabdosphincter are dose-dependent.     

Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility

The purpose of this study is to explore the feasibility of myoblasts, the precursors of muscle fibers, injected periurethrally as a potential treatment of stress urinary incontinence. We also studied myoblast injection into the bladder wall to potentially improve detrusor contractility. A myoblast cell line was transduced with adenovirus carrying the expression of the beta-galactosidase reporter gene while in culture. The cells were incubated with fluorescent latex microspheres (FLMs) to follow the outcome of the injected cells. The tissue was harvested 3-4 days after injection; sectioned, fixed, assayed for beta-galactosidase expression, and counterstained with H+E. Photographs of the slides were taken under light and fluorescence microscopy. We have noted a large number of cells expressing beta-galactosidase and containing FLMs in the urethral and bladder walls under fluorescent microscopy (8 animals). Many regenerative myofibers expressing beta-galactosidase were also seen in the urethral and bladder walls. The fusion of injected myoblasts to form myotubes was seen in both the urethral and bladder walls. The introduction of myoblasts into the urethral and bladder wall is feasible and results in formation of myotubes and myofibers in the smooth muscle layers of the lower urinary tract. We hypothesize that myoblast injections can be used as a non-allergenic agent to enhance urethral closure and bladder function.     

State of the art of where we are at using stem cells for stress urinary incontinence

AIMS: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors. METHODS: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory. RESULTS: In anatomical and functional studies of human and animal urethra, the middle urethra containing rhabdosphincter, is critical for maintaining continence. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as MDSCs and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. Not all cellular therapies are the same, as demonstrated by the differences in safety and efficacy from muscle-sourced MDSCs versus myoblasts versus fibroblasts. CONCLUSIONS: Transplanted stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. The dawn of a new paradigm in the treatment of SUI may be near.     

Improvement of urethral sphincter deficiency in female rats following autologous skeletal muscle myoblasts grafting

Sphincteric deficiency is the most common cause of urinary incontinence in humans. Various treatments have lead to disappointing results due to a temporary benefit. Recent studies raised the possibility that sphincteric deficiency could be treated by implanting skeletal myoblasts. In the present study, we developed in the female rat a model of chronic sphincteric defect to assess the benefit of myoblast injection. Sphincter deficiency was induced by freezing, longitudinal sphincterotomy, and notexin injection, respectively, to obtain a reproducible and irreversible incontinence. Autologous tibialis anteriors were cultured to be injected in the best model. Functional results were evaluated by measuring the urethral pressure with an open catheter. Histology was performed in the excised urethras. Of the three techniques, only longitudinal sphincterotomy caused definitive incontinence by irreversibly destroying the striated sphincter muscle fibers: a 45% decrease of the closure pressure was observed 21 days after the sphincterotomy. At this time, we injected myoblasts at the sphincterotomy site. In the sham-injected group (n = 18), the closure pressure decrease was not significantly modified 21 days after injection. By comparison, a return to near normal value was observed after cell grafting (n = 21). These results and those obtained by others strongly suggest that the use of myoblasts could be a potential innovative therapy for urethral deficiencies leading to incontinence.     

肌源细胞自体移植治疗前列腺术后尿失禁可行性的实验研究

目的:探讨自体骨骼肌肌源细胞(MDC)自体移植在前列腺术后尿失禁治疗中的可行性。方法:采用差速贴壁法分离、纯化培养6只雌性SD大鼠的MDC,然后用携带LacZ基因的腺病毒载体转染MDC,待转染成功后将约5×106携带LacZ基因的MDC自体注射于膀胱颈周围,注射后5、15d处死大鼠,取出膀胱及后尿道,注射部位组织行组织学检查及Xgal染色。结果:在注射后5、15d时注射部位无明显炎症改变及炎性细胞浸润,局部细胞层数增多。经Xgal染色显示各时间点均可见大量的细胞被蓝染,提示移植细胞在体内成活。结论:MDC自体膀胱尿道周围注射可长期存活,提示自体MDC移植有可能成为前列腺术后尿失禁治疗的一种有效方法。     

Can autologous myoblasts be used as a potential bulking agent?

OBJECTIVE

To investigate the behaviour of donor myoblasts at the vesico‐ureteric junction (VUJ) and to evaluate their potential as an autologous bulking agent, as myoblast transplantation has been shown to regenerate damaged or degenerated tissue, and it was postulated that they could be used to treat vesico‐ureteric reflux.

MATERIALS AND METHODS

Muscle biopsies were obtained from the lower limb muscles of 10 pigs. The quality of the cells was evaluated by electrophysiological and immunohistochemical tests. The cell membranes of myoblasts were labelled with PKH26, a fluorescent dye. Six weeks after taking of the muscle biopsies all pigs underwent cell transplantation; 30 × 10⁶ cells suspended in transplantation medium (in 1‐mL syringes) were injected at the VUJ, into the proximal urethra and the rhabdosphincter. At the VUJ volumes of 1 mL were injected, whereas in the urethra and rhabdosphincter small cell depots (0.1 mL) were injected. All the pigs were killed 8 weeks later, and the myoblasts and newly formed myofibres were identified using fluorescence microscopy, with a histological evaluation and investigation of potential local inflammatory reaction.

RESULTS

Two to three intact layers of autologous myoblasts were found in the outer aspects of the large cell depots in the VUJ. Immunohistochemistry further showed that the myoblasts were only viable at these outermost borders of the large bulking areas, whereas necrosis with red fluorescent cell detritus was visible in the remaining central aspects of the large bulk of cells. By contrast, cells survived and formed myotubes in the wall of the proximal urethra and the rhabdosphincter where the small cell depots had been injected.

CONCLUSIONS

In small depots, transplanted autologous myoblasts can survive and differentiate into myofibres, while in a large bulk of cells the vast majority of cells become necrotic. The present results show that myoblasts cannot be used for augmentation of large volumes of tissue or as a bulking agent.     

Membrane properties of single muscle cells of the rhabdosphincter of the male urethra

BACKGROUND: The electrophysiological properties of myoblast cultures established from the human and porcine rhabdosphincter (RS) and porcine lower limb muscle (LLSKM) were studied to elucidate their potential for tissue engineering applications in the lower urinary tract. METHODS: Muscle biopsies were collected from the prostatic part of the RS, the RS of male pigs, and the porcine LLSKM. Ion channels were studied by means of the patch-clamp technique. RESULTS: Only one subtype each of voltage gated Na+ and Ca2+ channels was observed in porcine RS and LLSKM. Two types of voltage gated Ca2+ channels were identified in human RS cells. The porcine RS and LLSKM myoblasts displayed similar fusion competence. CONCLUSIONS: Porcine RS and LLSKM myoblasts and human RS and human skeletal muscle cells show a high degree of similarity. Injection of autologous skeletal muscle myoboblasts in the lower urinary tract might, therefore, represent a promising approach to treat stress incontinence after radical prostatectomy.     

肌源干细胞自体移植治疗压力性尿失禁的可行性研究

目的探讨鼠骨骼肌肌源干细胞(MDC)自体移植在压力性尿失禁治疗中的可行性。方法采用差速贴壁法分离、纯化培养6只雌性大鼠的MDC,体外脂质体介导法转染pEGFP-N1质粒入MDC,转染成功后将筛选的MDC注射于自体膀胱颈和尿道周围,5、15 d处死大鼠切取膀胱及后尿道,组织学检查观察注射组织形态学改善,免疫组化检测GFP蛋白的表达,观察MDC存活情况。结果5、15 d注射部位组织未见明显炎症改变及炎性细胞浸润,局部细胞层数增多,免疫组化显示各时间点大量细胞细胞质内可见棕黄色GFP蛋白表达,且在5、15 d两个时间点GFP阳性细胞数量和染色强度没有明显改变。结论MDC自体膀胱尿道周围注射可持续存活,自体MDC有可能成为治疗压力性尿失禁的一种理想材料。     

Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ

BACKGROUND: Adult heart lacks stem cells and cannot effectively regenerate. In contrast, skeletal muscle is constantly undergoing repair. We proposed to transplant immature skeletal myoblasts into injured myocardium. METHODS: Approximately 7x10(6) soleus skeletal myoblasts were expanded in vitro from adult New Zealand White rabbits (n = 23) whose posterior left ventricle was cryoinjured to create a transmural lesion. Autologous myoblasts (n = 18) or saline (n = 5) was transplanted into the central cryolesion at the time of injury (n = 6) or 1 week later (n = 12). Hearts were harvested 2 weeks after injection. RESULTS: Myoblast transfer did not incur further morbidity. After cryolesion, grossly, a 1.6-cm epicardial hemorrhagic lesion could be seen. Histologically, the transmural lesion contained inflammatory cells and active scarring but no viable cardiomyocytes. Electron microscopy demonstrated a predominance of collagen and fibroblasts. Nine hearts contained multinucleated cells within the cryolesion that covered approximately 75% of the central cryolesion in 17% of animals. Immunohistochemical analysis confirmed their skeletal muscle origin. At the periphery of the lesion, isolated clusters of nonskeletal muscle cells could be visualized (n = 12) that resembled immature cardiocytes. CONCLUSIONS: Autologous skeletal myoblasts can regenerate viable striated tissue within damaged myocardium. Myoblast transfer warrants further investigation as a new method for improving myocardial performance within infarcted myocardium.     

Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: Report of two initial cases

Objectives:   To report a novel cell therapy using autologous adipose tissue-derived stem cells (ADSC) for stress urinary incontinence caused by urethral sphincteric deficiency and the outcomes in two initial cases undergoing periurethral injection of stem cells for the treatment of urinary incontinence after radical prostatectomy.
Methods:   Two patients with moderate stress incontinence after radical prostatectomy were enrolled. After liposuction of 250 mL of adipose tissue from the abdomen, we isolated ADSC from this tissue by using the Celution system. Subsequently, the isolated ADSC and a mixture of stem cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 12-week follow-up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography, and magnetic resonance imaging.
Results:   Urinary incontinence progressively improved after 2 weeks of injection up to 12 weeks in terms of decreased leakage volume in a 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life as per the questionnaire. In urethral pressure profile, both maximum urethral closing pressure and functional profile length increased. Ultrasonography and magnetic resonance imaging showed sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively.
Conclusion:   This preliminary study showed that periurethral injection of the autologous ADSC is a safe and feasible treatment modality for stress urinary incontinence.     

Pubovaginal slings for stress urinary incontinence following radical cystectomy and orthotopic neobladder reconstruction in women

PURPOSE: We evaluated the clinical efficacy of pubovaginal slings for new onset stress urinary incontinence following radical cystectomy and orthotopic lower urinary tract reconstruction in women. MATERIALS AND METHODS: Between June 1990 and July 2002, 101 female patients with primary transitional cell carcinoma of the bladder were treated with radical cystectomy and orthotopic ileal neobladder reconstruction. Four patients 61 to 73 years old underwent pubovaginal slings (autologous rectus fascia in 2 and dermal graft in 2) for stress urinary incontinence persisting 9 to 20 months following reconstruction with a Studer (2) or T pouch (2) ileal neobladder. Pre-cystectomy continence was excellent in 3 patients, while 1 had mild stress incontinence. All patients had high grade, muscle invasive transitional cell carcinoma and/or carcinoma in situ with negative urethral margins and 3 of the 4 had lymph node negative disease on pathological examination. Two patients were treated with transurethral bulking material 4 to 5 months prior to the sling procedure without noticeable improvement. RESULTS: Two patients who underwent autologous pubovaginal slings had significant complications arising from dissection in the retropubic space, including 1 entero-pouch fistula and 1 enterotomy resulting in an enterocutaneous fistula, sepsis and subsequent death. These 2 patients had persistent stress incontinence despite the sling procedures and they ultimately underwent conversion to continent cutaneous urinary diversions. Two patients were treated with a dermal graft sling using infrapubic bone anchors through a transvaginal approach, obviating the need to enter the pelvis. These patients had uneventful postoperative courses and they are currently hypercontinent, performing intermittent catheterization with complete daytime continence and only occasional nighttime leakage 3 and 9 months following sling surgery. CONCLUSIONS: Pubovaginal sling procedures for incontinence following orthotopic neobladder reconstruction in women may be complicated due to extensive pelvic surgery. Dissection in the retropubic space should be avoided because potentially fatal complications may occur. Slings using infrapubic bone anchors may provide the best option in such patients in whom conservative management has failed because the pelvis need not be violated.     

加速康复外科理念下针刺治疗腹腔镜下前列腺癌根治术后尿失禁的疗效观察

目的基于加速康复外科理念下观察针刺治疗腹腔镜下前列腺癌根治术后尿失禁的临床疗效。方法将2018年1月至2019年11月青岛市市立医院收治的48例腹腔镜下前列腺癌根治术后尿失禁患者,分为试验组和对照组(每组24例),试验组采用针刺联合盆底肌训练疗法,对照组采用盆底肌训练法。观察两组患者在治疗前后控尿的变化。结果两组组内治疗前后相比1 h尿垫试验漏尿量(g)、ICIQ-SF评分、24 h尿失禁次数均有改善;试验组治疗后各项观察指标均显著低于对照组,总有效率、治愈率均显著高于对照组;两组未见明显不良反应。结论针刺能够有效改善腹腔镜下前列腺癌根治术后患者尿失禁症状,促进尿控功能的恢复,符合加速外科康复理念,值得推广。     

Periurethral injection of autologous adipose‐derived regenerative cells for the treatment of male stress urinary incontinence: Report of three initial cases

Objectives: To report a novel cell therapy using autologous adipose tissue‐derived regenerative cells for male stress urinary incontinence caused by urethral sphincteric deficiency, and the outcomes in the initial cases undergoing periurethral injection of adipose tissue‐derived regenerative cells. Methods: Three patients with moderate stress incontinence after radical prostatectomy and holmium laser enucleation of the prostate were enrolled. Adipose tissue‐derived regenerative cells were isolated from the abdominal adipose tissue by using the Celution system. Subsequently, the isolated adipose tissue‐derived regenerative cells, and a mixture of adipose tissue‐derived regenerative cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short‐term outcomes during a 6‐month follow up were assessed by a 24‐h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography and magnetic resonance imaging. Results: Urinary incontinence progressively improved after 2 weeks of injection up to 6 months in terms of decreased leakage volume, decreased frequency and amount of incontinence, and improved quality of life. Both maximum urethral closing pressure and functional profile length increased. Magnetic resonance imaging suggested a sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri‐ and postoperatively. Conclusion: These preliminary findings suggest that periurethral injection of the autologous adipose tissue‐derived regenerative cells is a safe and feasible treatment modality for male stress urinary incontinence.     

Human myoblast engraftment is improved in laminin-enriched microenvironment

BACKGROUND: One major challenge in developing cell therapy for muscle diseases is to define the best condition for the recipient's muscle to niche donor cells. We have examined the efficiency of human myoblast transplantation in an immunodeficient animal model, after local irradiation, as well as the potential impact of laminin on myoblast behavior. METHODS: Human myoblasts were injected into preirradiated tibialis anterior muscles from immunodeficient mice. The donor cell engraftment, proliferation, and laminin content within the transplanted muscles were evaluated by immunocytochemistry. Additionally, the effect of laminin upon myoblast proliferation, migration, and survival was ascertained in vitro. RESULTS: Engraftment of human myoblasts into the skeletal muscle of immunodeficient Rag2-/gammac-/C5- mice presubjected to local irradiation provided the best niche for myoblast engraftment, as demonstrated by the number of viable and proliferating donor cells found in the host muscle. Local irradiation significantly enhanced laminin deposition within the recipient's muscle and donor cells were preferentially located in laminin-enriched areas. The same batch of myoblasts used for in vivo injections also responded to laminin in vitro with increased proliferation and cell survival, as well as an improved migratory response. CONCLUSIONS: We show that local irradiation enhances the laminin content in the host muscle microenvironment and provides a better engraftment of human myoblasts. In addition, laminin increases myoblast proliferation, survival, and migration in vitro. These data provide combined in vivo and in vitro evidence that laminin status should be taken into account when designing experimental and clinical cell therapy strategies for muscle disease.