Effect of Muscle Derived Stem Cells on the Restoration of Corpora Cavernosa Smooth Muscle and Erectile Function in the Aged Rat

Nolazco, Gaby; Kovanecz, Istvan; Vernet, Dolores; Ferrini, Mónica G.; Gelfand, R; Tsao, James; Magee, Thomas R.; Rajfer, Jacob; González‐Cadavid, Néstor F.

doi:10.1016/s0022-5347(08)60983-0

Cited by 30 publications

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“…Nolazco et al . [20] found that after 2 weeks of being injected with 0.5 × 10 6 to 1 × 10 6 MDSCs, the maximal intracavernosal pressure to mean arterial pressure ratio in aged rats was significantly increased to 1.13, a value above that usually seen in adult rats (0.8). When another series of rats were tested 4 weeks after MDSC transplantation, the mean maximal intracavernosal pressure/mean arterial pressure ratio had decreased to 0.72.…”

Section: Discussionmentioning

confidence: 81%

“…Based on immunocytohistology and SEM findings, MDSC are particularly attractive candidates for TECC tissue. In recent years, the development of erectile dysfunction therapy via adult stem cells [18–20] and the application of MDSCs in regenerative medicine [21,22] have expanded the therapeutic techniques that can be employed for penile reconstruction. Nolazco et al .…”

Section: Discussionmentioning

confidence: 99%

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Construction of tissue‐engineered corpus cavernosum with muscle‐derived stem cells and transplantationin vivo

Min

Liang

et al. 2010

BJU International

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Study Type – Therapy (case series)  Level of Evidence 4 What’s known on the subject? and What does the study add? The tissue‐engineered research of corpus cavernosum has been studied, but an ideal method was not carried out. In the study, muscle‐derived stem cells were used as seeding cells to construct tissue‐engineered corpus cavernosums. The result demonstrated MDSCs could be seeded on three‐dimensional scaffolds of acellular corporal collagen matrices and developed into tissues similar to native corpus cavernosum in vivo. OBJECTIVE To investigate the feasibility of tissue‐engineered corpus cavernosum (TECC) with muscle‐derived stem cells (MDSCs) as seed cells and determine the growth potential in vivo. MATERIALS AND METHODS Acellular corporal collagen matrices (ACCMs) were obtained from adult rabbit penis by a cell removal procedure. MDSCs were separated and purified using a digestion method and Preplate technique, then seeded on ACCMs at a concentration of 30 × 106 cells/mL to construct TECCs. After 5 days of culture, seeded ACCMs were implanted with albuginea of rabbits. The implants were retrieved at 2, 4 and 6 months after implantation. Histochemistry, immunohistochemisry and scanning electron microscopy were performed to analyse the morphological characteristics of the TECCs. RESULTS The decellularization process successfully extracted all cellular components while preserving the original collagen fibres. Histological analyses of the explants at all time points in the experimental group had more cells and better arranged growth than the control group. α‐Smooth muscle actin and endothelial nitric oxide synthase‐positive cells were more prevalent in the experimental group. CONCLUSION Our study showed that MDSCs can be seeded on three‐dimensional ACCM scaffolds and develop tissues that are similar to native normal corpus cavernosum.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Construction of tissue‐engineered corpus cavernosum with muscle‐derived stem cells and transplantationin vivo

Min

Liang

et al. 2010

BJU International

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“…Homogenates of frozen tissue (100 mg) were obtained in T‐PER (Pierce, Rockford, IL, USA) and protease inhibitors (3 µM leupeptin, 1 µM pepstatin A, 1 mM phenyl methyl sulphonyl fluoride), and centrifuging at 10 000 g for 5 min [42]. Equal amounts of supernatant protein (30 µg) were run on 7.5% and 10% (for αSMA) polyacrylamide gels, and submitted to Western blot immunodetection with a monoclonal antibody against PCNA (1:200 as described above), or a polyclonal against calponin (1:500; Santa Cruz, Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction

et al. 2009

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the pro-fibrotic transforming growth factor (TGF) β 1. The turnover of SMCs was assessed by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick-end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) assays. Quantitative Western blots determined calponin (SMC marker) and PCNA, and hydroxyproline was used for collagen. In vitro relaxation of corporal strips was measured. RESULTSIn vitro relaxation of corporal tissue from OZR was considerably less than in the LZR. In the media of the penile dorsal artery (PDA) of OZR, there was a considerable reduction in the SMC content and the SMC/collagen ratio, as well as an increase in apoptosis, but there were no changes in PCNA or TGF β 1 expression, or in the intima-media/lumen ratio. In the aorta of the OZR, in contrast to the PDA, there was a reduction in PCNA as well as a more pronounced decrease in the SMC/collagen ratio, mainly from an increase in collagen, but there were no changes in TGF β 1 or the wall/lumen morphometry. In the OZR, Western blots of aortic tissue confirmed the decrease in PCNA and a reduction in the SMC marker calponin. CONCLUSIONSThese data show that 5 months after the onset of hyperglycaemia in the OZR, the rats develop both abnormal corporal SMC relaxation and a generalized fibrosis of the arterial media of both the large and small diameter vessels. It is possible that this panfibrosis of the media of the arterial system might contribute to the diabetes-related ED that occurs during this period in this rat model.

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“…An emerging approach to treat corporal fibrosis is the replacement of the lost SMCs by implanted stem cells (Bivalacqua et al, 2007; Song et al, 2007). It was recently demonstrated that stem cells isolated from the skeletal muscle of mice can be implanted into the rat corpora cavernosa of old rats with ED and generate SMCs (Nolazco et al, 2008). By undergoing this conversion, the muscle‐derived stem cells corrected the ED in the aged rats.…”

Section: Proposed Amelioration and Reversal Of Penile Fibrosismentioning

confidence: 99%

Amelioration of Penile Fibrosis: Myth or Reality

El‐Sakka

Yassin

2010

Journal of Andrology

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Several changes have been reported to occur in the cavernosal tissue and tunica albuginea with aging. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction in the number of smooth muscle cells (SMCs) has been demonstrated in relation to this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance with aging. Chronic ischemia is therefore associated with fibrosis but also with nitric oxide-cGMP reduction. The sensitivity of the a-adrenoceptors on the SMCs increases with aging. Furthermore, androgen deprivation produces penile tissue atrophy, alterations in dorsal nerve structure, alterations in endothelial morphology, reductions in trabecular SM content, increases in deposition of extracellular matrix, and increases in accumulation of adipocytes in the subtunical region of the corpus cavernosum. All of these modifications can explain the prevalence of erectile dysfunction with aging. The aim of this review is to address the underlying etiology of corporal fibrosis, especially aging, cavernosal nerve damage, androgen deprivation, and tunical fibrosis. Finally, we will address the proposed amelioration and reversal of fibrosis in terms of correcting, at least partially, the relative SMC loss that occurs with aging, diabetes, or cavernosal nerve damage and its impact on prevention of erectile dysfunction-associated cavernosal fibrosis.

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Effect of Muscle Derived Stem Cells on the Restoration of Corpora Cavernosa Smooth Muscle and Erectile Function in the Aged Rat

Cited by 30 publications

References 0 publications

Construction of tissue‐engineered corpus cavernosum with muscle‐derived stem cells and transplantationin vivo

Construction of tissue‐engineered corpus cavernosum with muscle‐derived stem cells and transplantationin vivo

Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction

Amelioration of Penile Fibrosis: Myth or Reality

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