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Purpose: Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) imaging significantly improved the detection of recurrent prostate cancer (PCa). However, the value of PSMA PET imaging in patients with advanced hormone-sensitive or hormone-resistant PCa is still largely unknown. The aim of this study was to analyze the detection rate and distribution of lesions using PSMA PET imaging in patients with advanced PCa and ongoing androgen deprivation therapy (ADT). Methods: A total of 84 patients diagnosed with hormone-sensitive or hormone-resistant PCa who underwent $^{68}$Ga-PSMA-11 PET/magnetic resonance imaging (MRI) or computer tomography (CT) under ongoing ADT were retrospectively analyzed. We assessed the detection of PSMA-positive lesions overall and for three PSA subgroups (0 to < 1 ng/mL, 1 to < 20 ng/mL and > 20 ng/mL). In addition, PSMA-positive findings were stratified by localization (prostatic fossa, pelvic, para-aortic, mediastinal/supraclavicular and axillary lymph nodes, bone lesions and visceral lesions) and hormone status (hormone-sensitive vs. hormone-resistant). Furthermore, we assessed how many patients would be classified as having oligometastatic disease (≤ 3 lesions) and theoretically qualify for metastasis-directed radiotherapy (MDRT) in a personalized patient management. Results: We detected PSMA-positive lesions in 94.0% (79 of 84) of all patients. In the three PSA subgroups detection rates of 85.2% (0 to < 1 ng/mL, n = 27), 97.3% (1 to < 20 ng/mL, n = 37) and 100% (> 20 ng/mL, n = 20) were observed, respectively. PSMA-positive visceral metastases were observed only in patients with a PSA > 1 ng/mL. Detection of PSMA-positive lesions did not significantly differ between patients with hormone-sensitive and hormone-resistant PCa. Oligometastatic PCa was detected in 19 of 84 patients (22.6%). Almost all patients, 94.7% (n = 18) would have been eligible for MDRT. Conclusions: In this study, we observed an overall ver

BACKGROUND: Dutasteride has been shown to increase expression of the prostate-specific membrane antigen (PSMA) in prostate cancer cells in previous in vitro studies. This 5-alpha-reductase inhibitor is commonly used for the treatment of symptomatic benign prostatic enlargement. The modulation of PSMA expression might affect PSMA-based prostate cancer imaging and therapy. AIM: The purpose of this work was to further analyze concentration-dependent effects of Dutasteride on PSMA expression in a mouse xenograft model. METHODS AND RESULTS: Four groups of mice bearing LNCaP xenografts were treated for 14 days with daily intraperitoneal injections of either vehicle control or different concentrations of Dutasteride (0.1, 1, 10 mg/kg). Total expression of PSMA, androgen receptor (AR), and caspase-3 protein was analyzed using immunoblotting (WES). In addition, PSMA, cleaved caspase-3 and Ki-67 expression was assessed and quantified by immunohistochemistry. Tumor size was measured by caliper on day 7 and 14, tumor weight was assessed following tissue harvesting. The mean PSMA protein expression in mice increased significantly after treatment with 1 mg/kg (10-fold) or 10 mg/kg (sixfold) of Dutasteride compared to vehicle control. The mean fluorescence intensity significantly increased by daily injections of 0.1 mg/kg Dutasteride (1.6-fold) as well as 1 and 10 mg/kg Dutasteride (twofold). While the reduction in tumor volume following treatment with high concentrations of 10 mg/kg Dutasteride was nonsignificant, no changes in AR, caspase-3, cleaved caspase-3, and Ki-67 expression were observed. CONCLUSION: Short-term Dutasteride treatments with concentrations of 1 and 10 mg/kg significantly increase the total PSMA protein expression in a mouse LNCaP xenograft model. PSMA fluorescence intensity increases significantly even using lower daily concentrations of 0.1 mg/kg Dutasteride. Further investigations are needed to elucidate the impact of Dutasteride treatment on PSMA expressi

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.

OBJECTIVE To investigate the rate of erectile dysfunction (ED) after pelvic ring fracture (PRF). DESIGN Systematic review and meta-analysis. METHODS A systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus and Web of Science Library databases was conducted in January 2020. Included were original studies performed on humans assessing ED after PRF according to the 5-item International Index of Erectile Function (IIEF-5) questionnaire and fracture classification following Young and Burgess, Tile or Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association. Furthermore, interventional cohort studies assessing the effect of penile rehabilitation therapy with phosphodiesterase-5-inhibitors (PDE-5-I) on IIEF-5 scores compared before and after treatment were included. Results were presented as forest plots of proportions of patients with ED after PRF or mean changes on IIEF-5 questionnaires before and after penile rehabilitation. Studies not included in the quantitative analysis were narratively summarised. Risk of bias assessment was conducted using the revised tool for the Quality Assessment on Diagnostic Accuracy Studies. RESULTS The systematic literature search retrieved 617 articles. Seven articles were included in the qualitative analysis and the meta-analysis. Pooled proportions revealed 37% of patients with ED after suffering any form of PRF (result on probability scale pr=0.37, 95% CI: 0.26 to 0.50). Patients after 3 months of penile rehabilitation therapy reported a higher IIEF-5 score than before (change score=6.5 points, 95% CI: 2.54 to 10.46, p value=0.0013). CONCLUSION Despite some heterogeneity and limited high-quality research, this study concludes that patients suffering from any type of PRF have an increased risk of developing ED. Oral intake of PDE-5-I for the purpose of penile rehabilitation therapy increases IIEF-5 scores and may relevantly influence quality-of-life in these patients. PROSPERO REGISTRATION NUMBER CRD420201

Purpose: Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations. Methods: RPE specimens of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis. Results: All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. Conclusions: We describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach. Keywords: Glutamate carboxypeptidase II; Immunohistochemistry; Neoplas

Purpose: Ultrasound-guided biopsy (US biopsy) with 10-12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)-guided biopsy is recommended, despite a low specificity for lesions with score 3-5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with 68Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. Methods: Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. Results: SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. Conclusion: PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy. Trial registration: This trial was retrospectively registered under the name "Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in

BACKGROUND Positron emission tomography (PET) targeting the prostate-specific membrane antigen (PSMA) has superior sensitivity over conventional imaging (CI) to stage prostate cancer (PCa) and therefore is increasingly used in staging to stratify patients before radical therapy. Whether this improved diagnostic accuracy translates into improved outcome after radical prostatectomy (RPE) has not yet been shown. Therefore, the aim of this study was to compare the oncological outcome after RPE between patients that underwent preoperative staging with CI or PSMA-PET for intermediate and high-risk PCa. METHODS We retrospectively selected all patients that underwent RPE for intermediate- or high-risk PCa at our institution before PSMA-PET introduction (between March 2014 and September 2016) and compared the oncologic outcome of patients staged with PSMA-PET (between October 2016 and October 2018). Oncological pre-surgical risk parameters (age, PSA, D'Amico score, biopsy-ISUP, and cT stage) were compared between the groups. Oncological outcome was determined as PSA persistence, nerve-sparing rate, and surgical margin status. Wilcoxon rank-sum, Fisher's, and chi-square tests where used for statistical testing. RESULTS One hundred five patients were included, 53 in the CI group and 52 in the PSMA-group. Patients in the PSMA group had higher ISUP grade (p < 0.001) and D'Amico score (p < 0.05). The rate of free surgical margins and PSA persistence after RPE was 64% and 17% for the CI and 77% and 6% for the PSMA group (p = 0.15 and 0.13, respectively). Subgroup analysis with high-risk patients revealed PSA persistence in 7% (3/44) in the PSMA group and 25% (7/28) in the CI group (p = 0.04). Limitations include the retrospective design and choline-PET for some patients in the CI group. CONCLUSION Immediate outcome after RPE was not worse in the PSMA group compared with the CI group, despite a higher-risk cohort. In a comparison of only high-risk patients, PSMA-PET staging was ass

A first analysis of simultaneous Ga-PSMA-11 PET/MRI showed some improvement in the detection of recurrent disease at low serum prostate specific antigen (PSA) values below 0.5 ng/ml compared to the already high detection rate of Ga-PSMA-11 PET/CT. We therefore focused on all patients with biochemical recurrence (BR) and PSA values ≤ 0.5 ng/ml to assess the detection rate for Ga-PSMA-11 PET/MRI. We retrospectively analyzed a cohort of 66 consecutive patients who underwent a Ga-PSMA-11 PET/MRI for BR with a PSA value ≤ 0.5 ng/ml at our institution. Median PSA level was 0.23 ng/ml (range: 0.03 - 0.5 ng/ml). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones or visceral organs was recorded. In addition, all scans with Ga-PSMA-11 PET/MRI positive lesions were retrospectively assessed to analyze if lesions were detected inside or outside of a standard salvage radiotherapy volume. Overall, in 36 of 66 patients (54.5%) PSMA-positive lesions were detected; in 26 of 40 (65%) patients with a PSA between 0.2 - 0.5 ng/ml and in 10 of 26 (38.5%) patients with a PSA < 0.2 ng/ml. Even at those low PSA values, only 8 of 66 (12.1%) patients had exclusive local recurrence. In 23 patients lymph nodes and in 5 patients bone metastases were detected on Ga-PSMA-11 PET/MRI. In 26 of 66 patients (39.4%) PSMA-positive lesions were located outside a standard salvage radiotherapy volume. Our data confirm that Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer, even at low PSA levels ≤ 0.5 ng/ml. In addition, we show that Ga-PSMA-11 PET/MRI detected PSMA-positive lesions outside a standard salvage radiotherapy volume in 39.4% of all patients.

PURPOSE: To externally validate recently published prostate cancer risk calculators (PCa-RCs) incorporating multiparametric magnetic resonance imaging (mpMRI) for the prediction of clinically significant prostate cancer (csPCa) and compare their performance to mpMRI-naïve PCa-RCs. MATERIAL AND METHODS: Men without previous PCa diagnosis undergoing transperineal template saturation prostate biopsy with fusion-guided targeted biopsy between 11/2014 and 03/2018 in our academic tertiary referral center were identified. Any Gleason pattern ≥4 was defined to be csPCa. Predictors (age, PSA, DRE, prostate volume, family history, previous prostate biopsy and highest region of interest according to PIRADS) were retrospectively collected. Four mpMRI-PCa-RCs and two mpMRI-naïve PCa-RCs were evaluated for their discrimination, calibration and clinical net benefit using a ROC analysis, calibration plots and a decision curve analysis, respectively. RESULTS: Out of 468 men, 193 (41%) were diagnosed with csPCa. Three mpMRI-PCa-RCs showed similar discrimination with area-underneath-the-receiver-operating-characteristic-curves (AUC) from 0.83 to 0.85, which was significantly higher than the other PCa-RCs (AUCs: 0.69-0.74). Calibration-in-the-large showed minimal deviation from the true amount of csPCa by 2% for two mpMRI-PCa-RCs, while the other PCa-RCs showed worse calibration (11-27%). A clinical net benefit could only be observed for three mpMRI-PCa-RCs at biopsy thresholds ≥15%, while none of the six investigated PCa-RCs demonstrated clinical utility against a biopsy all strategy at thresholds <15%. CONCLUSIONS: Performance of the mpMRI-PCa-RCs varies, but they generally outperform mpMRI-naïve PCa-RCs in regard to discrimination, calibration and clinical usefulness. External validation in other biopsy settings is highly encouraged.

PURPOSE To evaluate the role of preoperative multiparametric magnetic resonance imaging (MRI) as predictor of post-prostatectomy incontinence (PPI). METHODS We analyzed patients who underwent robot-assisted radical prostatectomy for localized prostate cancer at our institution between July 2015 and April 2017. In these patients, we measured the perfusion quality of the pelvic floor with contrast media kinetics in the preoperative MRI of the prostate and compared the levator ani muscle (region of interest) to the surrounding pelvic muscle structures (reference). Prospectively collected questionnaires regarding urinary incontinence were then evaluated 1 year postoperatively. Outcomes were dichotomized into "continent" (ICIQ-Score = 0-5) and "incontinent" (ICIQ-Score ≥ 6). In each patient, we determined the perfusion ratio of the levator ani muscle divided by the surrounding pelvic muscle structures and compared them among the groups. RESULTS Forty-two patients were included in the study (n = 22 in "continent", n = 20 in "incontinent" group). The median perfusion ratio from the continent group was significantly higher compared to the incontinent group (1.61 vs. 1.15; 95% CI 0.09-0.81, p = 0.015). The median perfusion ratio in "excellent" (ICIQ-Score = 0) was significantly higher than in "poor" (ICIQ-Score ≥ 11) outcomes (1.48 vs. 0.94; 95% CI 0.04-1.03, p = 0.036). Further, a higher perfusion ratio was negatively correlated with ICIQ-Score (r = - 0.33; 95% CI - 0.58 to 0.03; p = 0.031). CONCLUSIONS Our data demonstrate a promising new strategy to predict PPI through the perfusion quality of pelvic muscle structures with contrast media kinetics. This may facilitate preoperative patient consulting and decision-making.

Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa. Our objective was to investigate whether PSMA-expression patterns of the primary tumour on immunohistochemistry (IHC) are associated with PSMA-PET detection rate of recurrent PCa. Methods: Retrospective institutional review board approved single-centre analysis of patients who had undergone 68Ga-PSMA-11-PET for BCR after radical prostatectomy (RPE) between 04/2016 and 07/2019, with tumour specimens available for PSMA-IHC. Clinical information (age, PSA-level, ongoing androgen deprivation therapy (ADT), Gleason score) and PSMA-IHC of the primary tumour were collected and their relationship to results from PSMA-PET (positive/negative) was investigated using a multiple logistic regression analysis. Results: 120 PSMA-PET scans in 74 patients were available for this analysis. Overall detection rate was 62% (74/120 scans), with a mean PSA value at scan time of 0.99 ng/ml (IQR 0.32-4.27). Of the clinical factors, only PSA-level and ADT were associated with PSMA-PET positivity. The percentage of PSMA-negative tumour area on IHC (PSMA%neg) had a significant association to PSMA-PET negativity (OR = 2.88, p < 0.001), while membranous PSMA-expression showed no association (p = 0.73). The positive predictive value of PSMA%neg ≥ 50% for a negative PSMA-PET was 85% (13/11) and for a PSMA%neg of 80% or more, 100% (9/9). Conclusions: PSMA-negative tumour area on IHC exhibited the strongest association with negative PSMA-PET scans, beside PSA-level and ADT. Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA%neg ≥ 50%.

PURPOSE: To assess the value of the PI-RADS 2.1 scoring system in the detection of prostate cancer on multiparametric MRI in comparison to the standard PI-RADS 2.0 system and to assess its inter-reader variability. MATERIALS AND METHODS: This IRB-approved study included 229 patients undergoing multiparametric prostate MRI prior to MRI-guided TRUS-based biopsy, which were retrospectively recruited from our prospectively maintained institutional database. Two readers with high (reader 1, 6 years) and low (reader 2, 2 years) level of expertise identified the lesion with the highest PI-RADS score for both version 2.0 and 2.1 for each patient. Inter-reader agreement was estimated, and diagnostic accuracy analysis was performed. RESULTS: Inter-reader agreement on PI-RADS scores was fair for both version 2.0 (kappa: 0.57) and 2.1 (kappa: 0.51). Detection rates for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) were almost identical for both PI-RADS versions and higher for the more experienced reader (AUC, Reader 1: PCa, 0.881-0.887, csPCa, 0.874-0.879; Reader 2: PCa, 0.765, csPCa, 0.746-0.747; both p > 0.05), both when using a PI-RADS score of ≥ 4 and ≥3 as indicators for positivity for cancer. CONCLUSIONS: The new PI-RADS 2.1 scoring system showed comparable diagnostic performance and inter-reader variability compared to version 2.0. The introduced changes in the version 2.1 seem only to take effect in a very small number of patients.

BACKGROUND ARN-509 (Apalutamide) is a unique androgen receptor (AR) antagonist for the treatment of castration-resistant (CR) prostate cancer (PC). It inhibits AR nuclear translocation, DNA binding and transcription of AR gene targets. As dysregulation of autophagy has been detected in PC, the targeting of autophagy is a potential approach to overcome early therapeutic resistance. Therefore, we investigated the characteristics of autophagic response to ARN-509 treatment and evaluated the potential effect of a combination with autophagy inhibition. METHODS Human prostate cancer cells (LNCaP) were cultivated in a steroid-free medium. Cells were treated with ARN-509 (50 µM) alone or in combination with the autophagy inhibitors 3-methyladenine (3MA, 5 mM) or chloroquine (Chl, 20 µM) or with ATG5 siRNA knock-down. Cell viability and apoptosis were measured by flow cytometry and fluorescence microscopy. Autophagy was monitored by immunohistochemistry, AUTOdot and immunoblotting (WES). RESULTS Treatment with ARN-509 led to cell death of up to 37% with 50 µM and 60% with 100 µM by day 7. The combination of 50 µM ARN-509 with autophagy inhibitors produced a further increase in cell death by day 7. Immunostaining results showed that ARN-509 induced autophagy in LNCaP cells as evidenced by elevated levels of ATG5, Beclin 1 and LC3 punctuation and by an increase in the LC3-II band detected by WES. Autophagic flux was restored by the treatment of cells with Chl, intensifying the LC3-II band. These findings were further supported by an enhanced autophagosome punctuation observed by Autodot staining. CONCLUSIONS These data demonstrate that treatment with ARN-509 leads to increased autophagy levels in LNCaP cells. Furthermore, in combination with autophagy inhibitors, ARN-509 provided a significantly elevated antitumor effect, thus providing a new therapeutic approach potentially translatable to patients.

BACKGROUND: The injection of muscle precursor cells (MPC) into the external urinary sphincter muscle (EUS) is a promising therapeutic option for regenerative treatment of stress urinary incontinence (SUI). The objective of the present project was to conduct a pre-clinical trial to investigate the feasibility and accuracy of ultrasound (US) guided, transurethral injections into the EUS of female cadavers. METHODS: This is a prospective, anatomical, interventional and radiological cadaveric laboratory investigation. Two urologists performed transurethral US-guided injections to deliver nano-iron particles into the EUS. The intervention was performed in three unfixed, fresh female cadavers. Each cadaver received MRI before and CT as well as MRI of the pelvis after the injections. RESULTS: The precision and accumulation of nano-iron particles in the EUS was compared using a rating scale to evaluate left versus right and anterior versus posterior distribution in axial and sagittal orientation with US, MRI and CT. The accuracy of our US-guided injections into the anterior target region yielded 4 points on the rating scale. Adequate precision and accumulation of particles in the left versus right EUS were also demonstrated (3 vs. 3.33 points, respectively). Signal intensity in MRI revealed a mean ratio of 0.33 before and after injection. CT scans showed no relevant artefacts impairing the assessment. CONCLUSION: US-guided, transurethral injection into the EUS is feasible and imaging reveals a precise accumulation in the target region. Our method provides an appropriate approach to deliver MPC in the EUS muscle for a regenerative treatment of SUI in the near future.

Introduction: All organs of human body are a conglomerate of various cell types with multidirectional interplay between the different cells and the surrounding microenvironment, leading to a stable tissue formation, homeostasis, and function. To develop a functional smooth muscle tissue, we need to simulate and create a multicellular microenvironment. The multilineage adipose-derived stem cells (ADSCs), which can be easily harvested in large numbers, may provide an alternative cell source for the replacement of smooth muscle cells (SMCs) in cell-based detrusor bioengineering therapeutic approaches. The aim of this study was to investigate whether predifferentiated smooth muscle-like ADSC (pADSC) can support SMCs to generate stable smooth muscle tissue through remodeling of extracellular matrix (ECM) and factor secretion. Methods: Rat SMC and pADSC were mono- and cocultured in the cell ratios 1:1, 1:2, 1:3, and 1:5 (SMC-pADSC) and grown for up to 2 weeks in vitro. The expression of the SMC-specific markers alpha-smooth muscle actin, calponin, myosin heavy chain 11 (MyH11), and smoothelin was assessed, and cell proliferation and contractility were analyzed. Proteomic analysis of the secretome (cell-cell contact was compared with a noncontact transwell 1:1 coculture) and the cell pellets was performed, with the focus on ECM deposition and remodeling, integrin expression and growth factor secretion. Results: SMC and pADSC were strongly positive for all smooth muscle markers. After 1 and 2 weeks of culture, the 1:1 cell ratio developed a significantly higher number of smooth muscle organoids and improved contractility. These organoids were highly structured, consisting of an SMC core surrounded by a pADSC layer. The deposition of various EMC proteins, such as collagens 1a1, 1a2, 2a1, 3a1, 5a2, 6a2, 12a1, and fibrillin 1, was significantly increased. A decreased matrix metalloproteinase 3 (MMP3), MMP9 and MMP13 secretion, as well as increased tissue inhibitors of metallop