Abstract
Erectile dysfunction is a common complication associated with type 2 diabetes mellitus (T2DM) and after prostatectomy in relation to cancer. The regenerative effect of cultured adipose-derived stem cells (ASCs) for ED therapy has been documented in multiple preclinical trials as well as in recent Pase 1 trials in humans. However, some studies indicate that diabetes negatively affects the mesenchymal stem cell pool, implying that ASCs from T2DM patients could have impaired regenerative capacity. Here, we directly compared ASCs from age-matched diabetic Goto–Kakizaki (ASCGK) and non-diabetic wild type rats (ASCWT) with regard to their phenotypes, proteomes and ability to rescue ED in normal rats. Despite ASCGK exhibiting a slightly lower proliferation rate, ASCGK and ASCWT proteomes were more or less identical, and after injections to corpus cavernosum they were equally efficient in restoring erectile function in a rat ED model entailing bilateral nerve crush injury. Moreover, molecular analysis of the corpus cavernosum tissue revealed that both ASCGK and ASCWT treated rats had increased induction of genes involved in recovering endothelial function. Thus, our finding argues that T2DM does not appear to be a limiting factor for autologous adipose stem cell therapy when correcting for ED.
Highlights
The epidemic-like increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with numerous complications and reduced life quality for the patients, in addition to substantial societal economic costs related to treatment [1,2]
To determine whether the type 2 diabetic state has an effect on the regenerative potential of adiposederived stem cells (ASCs), we used the non-obese type 2 diabetic (GK) rats along with normal age-matched WT rats for isolation of donor ASCs
We obtained ASCs from GK- (ASCGK) and WT- (ASCWT) rats by harvesting SAT followed by stromal vascular fraction (SVF) isolation as established above
Summary
The epidemic-like increasing prevalence of type 2 diabetes mellitus (T2DM) is associated with numerous complications and reduced life quality for the patients, in addition to substantial societal economic costs related to treatment [1,2]. Diabetics experience ED earlier in life and in a more severe form than otherwise seen in the healthy male population [6]. It has profound negative effects on the life quality of the patients and their partners. We have previously demonstrated safety and potential therapeutic efficacy of freshly isolated SVF in a Phase I clinical trial treating ED patients following radical prostatectomy [19]. This underscores the potential benefit of ASCs for correcting ED.
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