Overexpression of ATF3 enhanced the therapeutic effects of human adipose-derived stem cells on erectile dysfunction associated with cavernous nerve injury

AbstractBackground Erectile dysfunction (ED) frequently arises as a prevalent complication following prostatectomy. Local administration of stem cells via penile injection has shown effectiveness in addressing erectile dysfunction stemming from bilateral cavernous nerve injury (BCNI-ED). Moreover, stem cell therapy, incorporating targeted genetic alterations, has the capacity to improve therapeutic results. This investigation involved the utilization of human Adipose-Derived Stem Cells (hASCs) that were genetically modified to overexpress activating transcription factor 3 (ATF3) and subsequently injected into the cavernous bodies of rat penises to enhance the therapeutic efficacy in cases of BCNI-ED. Methods Human adipose-derived stem cells (hASCs) were isolated, cultured, and characterized using flow cytometry, as well as subjected to osteogenic and adipogenic induction. Subsequently, the hASCs were transfected with lentivirus and assessed for the expression of nerve-associated growth factors. Following this, the treated hASCs were administered into the penises of rats with bilateral cavernous nerve injury-induced erectile dysfunction (BCNI-ED) to assess their therapeutic efficacy. The intracorporeal pressure/mean arterial pressure ratio (ΔICP/MAP) was utilized as a measure of erectile function. In vivo small animal imaging was conducted to monitor the distribution of the hASCs. Results hASCs showed increased expression of CD90, CD73, CD105 and decreased expression of CD45. ATF3-modified hASCs expressed nerve growth-related factors and had improved therapeutic potential in improving ΔICP/MAP ratio and α-SMA content while decreasing Collagen I content. In vivo imaging of small animals showed hASCs residing within the cavernous, with no group differences. Conclusions ATF3 enhanced neural-related trophic factor expression in hASCs, boosting their therapeutic potential of adipose stem cells on erectile dysfunction associated with cavernous nerve injury.