Scaffoldless Tissue Engineering of Stem Cell Derived Cavernous Tissue for Treatment of Erectile Function

摘要

Introduction. As one-third of erectile dysfunction (ED) patients do not respond to phosphodiesterase-5 inhibitors, there is great demand for new therapeutic options. Adipose tissue-derived stem cells (ADSCs) represent an ideal source for new ED treatment. Aim. To test if ADSCs can be differentiated into smooth muscle cells (SMCs) and endothelial cells (ECs), if these differentiated cells can be used to engineer cavernous tissue, and if this engineered tissue will remain for long time after implantation and integrate into corporal tissue. Method. Rat ADSCs were isolated and differentiated into SMC and ECs. The differentiated cells were labeled with 5-ethynyl-2-deoxyuridine (EdU) and used to construct cavernous tissue. This engineered tissue was implanted in penises of normal rats. The rats were sacrificed after 1 and 2 months; penis and bone marrow were collected to assess cell survival and inclusion in the penile tissues. Main Outcome Measures. The phenotype conversion was checked using morphology, immunocytochemistry (immunohistochemistry [IHC]), and Western blot for SMC and EC markers. The cavernous tissue formation was assessed using rat EC antibody (RECA), calponin, and collagen. The implanted cell survival and incorporation into penis were evaluated with hematoxylin and eosin, Masson's trichrome, and IHC (RECA, calponin, and EdU). Results. The phenotype conversion was confirmed with positive staining for SMC and EC markers and Western blot. The formed tissue exhibited architecture comparable to penile cavernous tissue with SMC and ECs and extracellular matrix formation. The implanted cells survived in significant numbers in the penis after 1 and 2 months. They showed proof of SMC and EC differentiation and incorporation into penile tissue. Conclusions. The results showed the ability of ADSCs to differentiate into SMC and ECs and form cavernous tissue. The implanted tissue can survive and integrate into the penile tissues. The cavernous tissue made of ADSCs forms new technology for improvement of in vivo stem cell survival and ED treatment.