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Noel N. Kim, Anita H. Clayton, Rachel N. Pauls, Hartmut Porst, Michael Krychman, Current Literature Review, The Journal of Sexual Medicine, Volume 10, Issue 1, January 2013, Pages 19–25, https://doi.org/10.1111/jsm.12073
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Effect of an adipose-derived stem cell and nerve growth factor-incorporated hydrogel on recovery of erectile function in a rat model of cavernous nerve injury. IG Kim, S Piao, JY Lee, SH Hong, TK Hwang, SW Kim, CS Kim, JC Ra, I Noh, JY Lee. Tissue Eng Part A 2012; E-pub ahead of print (doi: 10.1089/ten.tea.2011.0654).
Editorial Comment: Treatments to restore erectile function after radical prostatectomy have been actively investigated. One of the main therapeutic strategies has been to encourage nerve growth and repair through the local or systemic administration of growth factors. Recent experience with stem cell therapeutics has also sparked much interest in its potential to stimulate nerve regeneration and counteract adverse changes to cavernosal tissue health. Furthermore, the advent of stem cell isolation techniques from adult tissues (especially adipose tissue) has minimized the ethical dilemmas associated with embryonic stem cells and has made possible autologous cell donation protocols. Thus, growth factors and adipose-derived stem cells (ADSCs) have come to the forefront of research efforts. In this study, the investigators used a bilateral cavernous nerve crush injury rat model. Immediately after the nerve crush procedure, a preparation of human ADSC was applied over the area of injury and covered with hydrogel impregnated with nerve growth factor (NGF). The hydrogel consisted of biocompatible and biodegradable material with the added beneficial ability to bind proteins in the extracellular matrix and on the cell surface. In addition, pilot studies indicated that the hydrogel matrix released NGF for more than 30 days under tissue culture conditions. After 4 weeks, animals receiving combined treatment of ADSC and NGF exhibited statistically significant, but modestly higher, erectile activity than those treated with ADSC alone or NGF alone. All treatment groups had significantly better erectile responses when compared with untreated animals with nerve injury. In immunohistological studies, similar data trends were observed between treatment groups for endothelial nitric oxide synthase and α-smooth muscle actin staining. Fluorescently labeled ADSCs were associated with the cavernous nerve and colocalized to NGF staining. In comparison with animals treated with ADSCs alone, there was also an increased number of ADSCs localized to the cavernous nerve when NGF-incorporated hydrogel was applied. The authors postulated that these findings indicated engraftment of ADSCs to the cavernous nerve. This is only the second study to examine the effects of combined stem cell and growth factor therapy for cavernous nerve repair. A recently published study from the same group demonstrated similar findings when ADSC treatment was combined with brain-derived neurotrophic factor incorporated into a synthetic polysaccharide matrix. Given the fact that a significant portion of growth factors and stem cells administered by cavernous injection does not remain localized at the site of delivery, a biomatrix overlay to increase cell retention may be an advantageous strategy. In addition to translational research, future studies will be required to determine if there are additional real benefits to combined therapy vs. stem cells alone or growth factors alone.
