Treatment of Erectile Dysfunction in the Obese Type 2 Diabetic ZDF Rat with Adipose Tissue-Derived Stem Cells

Abstract

Introduction Impotence, or erectile dysfunction (ED), is a major complication of type-II diabetes, and many diabetic men with ED are refractory to common ED therapies. Aim To determine whether autologous adipose tissue derived stem cells (ADSC) injected into the penis of impotent obese type-II diabetic rats survive and improve erectile function. Main outcome measures Intracorporal pressure (ICP) increase with cavernous nerve (CN) electrostimulation, immunohistochemistry, real-time PCR, and serum glucose and testosterone assays. Methods Twenty-two 10-week old male fatty type-II diabetic ZDF rats underwent weight and blood glucose measurement every 2 weeks. At age 22 weeks, all animals underwent unilateral CN electrostimulation and ICP measurement to confirm impotence, and paragonadal adipose tissue (5 grams) was harvested and digested to yield 1.5 million ADSC. Impotent animals were randomized to ADSC treatment and sham control groups. At age 23 weeks, treatment group animals underwent penile injection of 1.5 million ADSC; control group animals received only PBS. Erectile function studies were repeated at age 26 weeks, followed by harvest of tissue and serum. Results Pre- and post-treatment stimulation ICP increase was significantly different between groups (p<0.002). In the control group, mean (SD) pre- and post-treatment stimulation ICP increase was 33.8 (15.9) and 31.4 (24.3) cmH2O, respectively, whereas in the treatment group they were 27.4 (14.8) and 65.3 (15.4) cmH2O. BrdU-labeled ADSC were observed within corporal tissue of the treatment group. TUNEL staining (p<0.0001) and caspase-3 m-RNA expression (p<0.05) were significantly higher within corporal tissue of control group versus treatment group animals. Conclusion Autologous ADSCs injected into the penis appear to survive and improve erectile function. Autologous ADSC therapy is a promising approach to treat diabetic impotence.

Isolation and passage of muscle-derived stem cells from the rat penile corpora cavernosa and induction of differentiation into smooth muscle cells

“…Some studies confirmed that embryonic stem cells can be used for the treatment of neurogenic ED (Eglitis and Mezey 1997). Studies of the effect of mesenchymal (Bivalacqua et al 2007;Qiu et al 2012), human neural crest (Song et al 2008), and adipose tissue-derived stem cells (Albersen et al 2010;Garcia et al 2010;Huang et al 2010) on ED treatment have also been performed by other researchers using intracavernous injection of these cells in rats. The results indicated that ED could be improved to a certain extent when treated with these cells.…”

Stem Cell Therapy for Erectile Dysfunction: A Critical Review

“…In all of our published SC-for-ED studies we reported difficulties in finding the transplanted SCs in penile tissues even though the animals clearly demonstrated functional and structural improvements [13,22,23,26]. In studies published by others, intracavernously injected SCs were similarly difficult to find.…”

Stem cells: novel players in the treatment of erectile dysfunction

“…Investigation of the long-term fate of ADSCs is required before human trials could be considered, although the lack of ADSCs in tissue sections observed for a 28-day follow-up period implies that the potential of these cells to persist and undergo malignant transformation is limited. 124 Second, Garcia and co-workers 125 observed improved erectile function in type-2 diabetic rats after autologous ADSC injection. This observation was based on decreased numbers of apoptotic cells in the corpus cavernosum, increased numbers of sinusoid ECs and increased expression of nNOS in the penile nerves.…”