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Reply: potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells

International Journal of Impotence Research volume 19, page 530 (2007)Cite this article

The recent article by Song et al. is scientifically sound and a welcome contribution to the innovative approach of employing cell-based therapy to treat erectile dysfunction (ED). In addition, this study underscores the particular benefits of using multi-potent mesenchymal stem cells (MSCs) as a donor graft.1 The intent of this study was to ascertain whether human MSCs (hMSCs) could engraft within the corporal tissue and differentiate into endothelial and smooth muscle cells. Fetal hMSCs were immortalized and injected into the corpora cavernosa of young rats. Following transplantation, the authors noted that the engrafted hMSCs began expressing endothelial and smooth muscle antigens. They concluded that immortalized hMSCs are able to differentiate into both endothelial and smooth muscle appearing cells. In addition, they advocated further research into whether hMSCs will respond similarly in the presence of cavernosal injury or in pathological disease states known to cause ED, such as diabetes and vascular disease.

In their discussion, the authors state, ‘It is not known whether the in vivo transplanted MSCs act completely as a mature ECs or SMCs in the early phase following transplantation’. Furthermore, they write, ‘…we do not know whether cellular therapy may help or hurt penile erectile function’. However, the authors fail to recognize earlier work using MSCs as a novel cell-based therapy for the treatment of vasculogenic-associated ED in an animal model of aging.2, 3, 4 Our laboratory using an animal model of aging demonstrated that rat MSCs (rMSCs) alone or when ex vivo gene-modified with endothelial nitric oxide synthase (eNOS) not only adopt the phenotype of ECs or SMCs in vivo, but also functionally improve erectile physiology and reverse age-associated ED.2, 3, 4 Following intracavernous injection of rMSCs alone or when transduced with eNOS, several physiological measures of erectile quality increased in accordance with upregulation of eNOS protein, calcium-dependent NOS activity and tissue cGMP levels. For the first time, these data demonstrated that eNOS-transduced and wild-type syngeneic rMSCs can be used to improve erectile function via mechanisms involving improved endothelial-derived NO biosynthesis and point out the clinical potential of using adult stem cell-based therapy for the treatment of ED.

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References

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Authors and Affiliations

  1. Johns Hopkins Hospital, Brady Urological Institute, Baltimore, MD, USA

    T D Strong & T J Bivalacqua

  2. Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD, USA

    H C Champion

  3. Department of Pharmacology, Tulane Health Sciences Center, New Orleans, LA, USA

    P J Kadowitz

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  1. T D Strong
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  2. H C Champion
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  3. P J Kadowitz
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  4. T J Bivalacqua
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Correspondence to T J Bivalacqua.

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Strong, T., Champion, H., Kadowitz, P. et al. Reply: potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells. Int J Impot Res 19, 530 (2007). https://doi.org/10.1038/sj.ijir.3901585

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