Abstract
The intracavernous (i.c.) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked i.c.-injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by i.c. injection of 1 million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received i.c. injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of i.c. injection and migrated preferentially to bone marrow. Allogenicity did not affect the bone marrow appearance of ADSCs at either 2 or 7 days, whereas CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed.
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References
Huang YC, Shindel AW, Ning H, Lin G, Harraz AM, Wang G et al. Adipose derived stem cells ameliorate hyperlipidemia associated detrusor overactivity in a rat model. J Urol 2010; 183: 1232–1240.
Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM et al. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy 2010; 12: 88–95.
Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 2011 (in press).
Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin CS et al. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int 2004; 94: 904–909.
Lin CS . Advances in stem cell therapy for the lower urinary tract. World J Stem Cells 2010; 2: 1–4.
Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin CS et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med 2010; 7: 3331–3340.
Garcia MM, Fandel TM, Lin G, Shindel AW, Banie L, Lin CS et al. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. J Sex Med 2010; 7 (1 Pt 1): 89–98.
Huang YC, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM et al. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med 2010; 7 (4 Pt 1): 1391–1400.
Abdel Aziz MT, El-Haggar S, Mostafa T, Atta H, Fouad H, Mahfouz S et al. Effect of mesenchymal stem cell penile transplantation on erectile signaling of aged rats. Andrologia 2010; 42: 187–192.
Bahk JY, Jung JH, Han H, Min SK, Lee YS . Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant 2010; 8: 150–160.
Qiu X, Lin H, Wang Y, Yu W, Chen Y, Wang R et al. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 2011; 8: 427–436.
Kendirci M, Trost L, Bakondi B, Whitney MJ, Hellstrom WJ, Spees JL . Transplantation of nonhematopoietic adult bone marrow stem/progenitor cells isolated by p75 nerve growth factor receptor into the penis rescues erectile function in a rat model of cavernous nerve injury. J Urol 2010; 184: 1560–1566.
Lin G, Bella AJ, Lue TF, Lin CS . Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part 2. J Sex Med 2006; 3: 821–827, discussion 828-829.
Christ GJ . The penis as a vascular organ. The importance of corporal smooth muscle tone in the control of erection. Urol Clin North Am 1995; 22: 727–745.
Lin G, Huang YC, Shindel AW, Banie L, Wang G, Lue TF et al. Labelling and tracking of mesenchymal stromal cells with EdU. Cytotherapy 2009; 11: 864–873.
Zhang H, Ning H, Banie L, Wang G, Lin G, Lue TF et al. Adipose tissue-derived stem cells secrete CXCL5 cytokine with chemoattractant and angiogenic properties. Biochem Biophys Res Commun 2010; 402: 560–564.
Zhang H, Yang R, Wang Z, Lin G, Lue TF, Lin CS . Adipose tissue-derived stem cells secrete CXCL5 cytokine with neurotrophic effects on cavernous nerve regeneration. J Sex Med 2011; 8: 437–446.
Fandel TM, Albersen M, Lin G, Qiu X, Ning H, Banie L et al. Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury. Eur Urol (submitted).
Han J, Koh YJ, Moon HR, Ryoo HG, Cho CH, Kim I et al. Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood 2010; 115: 957–964.
Massollo M, Podesta M, Marini C, Morbelli S, Cassanelli C, Pinto V et al. Contact with the bone marrow microenvironment readdresses the fate of transplanted hematopoietic stem cells. Exp Hematol 2010; 38: 968–977.
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This work was supported by grants from the Arthur Rock Foundation and the National Institutes of Health (DK045370).
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Lin, G., Qiu, X., Fandel, T. et al. Tracking intracavernously injected adipose-derived stem cells to bone marrow. Int J Impot Res 23, 268–275 (2011). https://doi.org/10.1038/ijir.2011.38
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DOI: https://doi.org/10.1038/ijir.2011.38
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