Stromal derived factor-1 treatment results in stem cell pathway activation in penile tissues and increased neurotrophins in major pelvic ganglion
Sopko, N1; Matsui, H2; Joice, G3; Bell, M3; Yoshida, T3; Liu, X3; Kates, M3; Bivalacqua, T3
1: The Johns Hopkins School of Medicine, United States; 2: The University of Tokyo; 3: The Johns Hopkins School of Medicine
Objective: Stromal derived factor-1 (SDF1) penile injections improve erectile physiology following bilateral cavernous nerve injury (BCNI). SDF1 activates and recruits stem cells. We investigated penile tissue stem cell activation and neurotrophin expression in the major pelvic ganglion (MPG) as possible mechanisms of SDF1 treatment.
Materials and Methods: Sprague Dawley (350g) male rats underwent sham procedure or BCNI (n=4/group). Starting on the day of surgery, BCNI animals received penile injections with 1ug of SDF1 or saline QOD for 5 injections. Sham animals received saline penile injections. 2 weeks after surgery, RNA was isolated from penile tissues and analyzed using a stem cell pathway expression array and normalized to sham animals (Qiagen, Germany). MPGs were isolated from male Sprague-Dawley rats (350g) and cultured in matrigel with serum free media for 72 hours with and without SDF1 treatment (500ng/mL, 4/group). Protein expression of 27 growth factors, cytokines, and neurotrophins were assessed using a protein array (Neuromics Edina, MN, USA).
Results: BCNI resulted in a 2.48 (p<0.0001) fold global increase in stem cell associated gene expression compared to sham animals, which was significantly increased compared to sham and saline animals with SDF1 treatment 4.80 fold (p<0.0001, respectively). SDF1 treatment resulted in upregulated gene expression in gene families of cell cycle regulators; cytokines and growth factors; cell communication; mesenchymal stem cell markers; notch pathway; and Wnt pathway. MPGs treated with SDF1 demonstrated increased protein levels in 9 growth factors including BDNF, IGF-1, bFGF, epidermal growth factor receptor, FGF7, growth hormone, bone morphogenetic protein 4, endocrine gland-derived vascular endothelial growth factor, and insulin-like growth factor binding protein 2 on protein array (n=4/group).
Conclusions: SDF1 increases stem cell activation in penile tissues and neurotrophin protein expression in the MPG suggesting its mechanisms may involve both stem cell activation and local beneficial effects of target tissues.
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