Skip to main content
SpringerLink
Log in

Erectile Function Restoration After Repair of Resected Cavernous Nerves by Adipose-Derived Stem Cells Combined with Autologous Vein Graft in Rats

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Cavernous nerve (CN) injury is the main cause of erectile dysfunction (ED) following radical prostatectomy. The recovery of erectile function following this procedure remains challenging. Here, we investigated the ability of adipose-derived stem cells (ADSCs) combined with autologous vein graft to improve erectile function in a rat model of bilateral long CN resection. Sprague–Dawley rats (n = 36) were randomized into four groups. Group A underwent sham operation. In Groups B, C, and D, an 8-mm segment of CN was excised bilaterally. In Group B and C, a 10-mm segment of autologous saphenous vein was interposed bilaterally at the site of injury, and the two nerve stumps were inserted into the vein lumen. 50 μL ADSCs were injected into each vein in Group B, and 50 μL of phosphate-buffered saline was injected in Group C. Group D underwent no repair. Erectile function assessed after 3 months by measuring intracavernosal pressure demonstrated significant recovery in erectile function in Group B with minimal recovery in Group C or D. Immunohistochemical staining showed that the nNOS-positive area was significantly larger in Group B than in Group D. ADSCs combined with autologous vein graft treatment had beneficial effects on the smooth muscle/collagen ratio in the corpus cavernosum. This procedure, therefore, provided a means of regenerating CN tissue and restoring autonomic erectile function after long bilateral CN resection (0.8 cm) in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin CS, Lue TF (2010) 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 7:3331–3340

    Article  PubMed  Google Scholar 

  • Bivalacqua TJ, Deng W, Kendirci M, Usta MF, Robinson C, Taylor BK, Murth SN, Champion HC, Hellstrom WJ, Kadowitz PJ (2007) Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol 292:1278–1290

    Article  Google Scholar 

  • Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin CS, Lue TF (2004) The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int 94:904–909

    Article  PubMed  Google Scholar 

  • Cai L, Johnstone BH, Cook TG, Tan J, Fishbein MC, Chen PS, March KL (2009) IFATS collection: human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 27:230–237

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Connolly S, Yoo J, Abouheba M, Soker S, Atala A (2008) Cavernous nerve regeneration using acellular nerve grafts. World J Urol 26:333–339

    Google Scholar 

  • Fandel T, Albersen M, Lin G, Qiu X, Ning H, Banie L, Lue TF, Lin CS (2012) 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 61:201–220

    Article  PubMed Central  PubMed  Google Scholar 

  • Hu WL, Hu LQ, Song J, Li SW, Zheng XM, Cheng B, Tian BC (2004) Fibrosis of corpus cavernosum in animals following cavernous nerve ablation. Asian J Androl 6:111–116

    CAS  PubMed  Google Scholar 

  • Hu W, Cheng B, Liu T, Li S, Tian Y (2010) Erectile function restoration after repair of excised cavernous nerves by autologous vein graft in rats. J Sex Med 7:3365–3372

    Article  PubMed  Google Scholar 

  • Jeon WJ, Kang JW, Park JH, Suh DH, Bae JH, Hong JY, Park JW (2011) Clinical application of inside-out vein grafts for the treatment of sensory nerve segmental defect. Microsurgery 31:268–273

    Article  PubMed  Google Scholar 

  • Kendirci M, Trost L, Bakondi B, Whitney MJ, Hellstrom WJ, Spees JL (2010) 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 184(4):1560–1566

    Article  PubMed Central  PubMed  Google Scholar 

  • Lin G, Albersen M, Harraz AM, Fandel TM, Garcia M, McGrath MH, Konety BR, Lue TF, Lin CS (2011) Cavernous nerve repair with allogenic adipose matrix and autologous adipose-derived stem cells. Urology 77(1509):e1–e8

    Google Scholar 

  • Lindroos B, Suuronen R, Miettinen S (2011) The potential of adipose stem cells in regenerative medicine. Stem Cell Rev 7:269–291

    Article  PubMed  Google Scholar 

  • May F, Matiasek K, Vroemen M, Caspers C, Mrva T, Arndt C, Schlenker B, Gais P, Brill T, Buchner A, Blesch A, Hartung R, Stief C, Gansbacher B, Weidner N (2008) GDNF-transduced Schwann cell grafts enhance regeneration of erectile nerves. Eur Urol 54:1179–1187

    Article  PubMed  Google Scholar 

  • Mikos AG, Bao Y, Cima LG, Ingber DE, Vacanti JP, Langer R (1993) Preparation of poly(glycolic) acid bonded fiber structures for cell attachment and transplantation. J Biomed Mater Res 27:183–189

    Article  CAS  PubMed  Google Scholar 

  • Molander H, Olsson Y, Engkvist O, Bowald S, Eriksson I (1982) Regeneration of peripheral nerve through a polyglactin tube. Muscle Nerve 5:54–57

    Article  CAS  PubMed  Google Scholar 

  • Muneuchi G, Kuwata Y, Taketa S, Inui M, Tsukuda F, Shimada O, Igawa HH, Kakehi Y (2005) Cavernous nerve reconstruction during radical prostatectomy by sural nerve grafting: surgical technique in nerve harvesting and grafting. J Reconstr Microsurg 21:525–532

    Article  PubMed  Google Scholar 

  • Qiu X, Lin H, Wang Y, Yu W, Chen Y, Wang R, Dai Y (2011) Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med 8:427–436

    Article  PubMed  Google Scholar 

  • Qiu X, Fandel T, Ferretti L, Albersen M, Zhang H, Lin G, Lin CS, Schroeder T, Lue TF (2012) Both immediate and delayed intracavernous injection of autologous adipose-derived stromal vascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury. Eur Urol 62:720–727

    Article  PubMed Central  PubMed  Google Scholar 

  • Quinlan DM, Nelson RJ, Walsh PC (1991) Cavernous nerve grafts restore erectile function in denervated rats. J Urol 145:380–383

    CAS  PubMed  Google Scholar 

  • Scardino PT, Kim ED (2001) Rationale for and results of nerve grafting during radical prostatectomy. Urology 57:1016–1019

    Article  CAS  PubMed  Google Scholar 

  • Williams LR (1987) Rat aorta isografts process nerve regeneration-promoting properties in silicon Ychambers. Exer Neuro 93:555–563

    Article  Google Scholar 

  • Wolford LM, Rodrigues DB (2011) Autogenous grafts/allografts/conduits for bridging peripheral trigeminal nerve gaps. Atlas Oral Maxillofac Surg Clin N Am 19:91–107

    Article  Google Scholar 

  • Ying C, Hu W, Cheng B, Zheng X, Li S (2012) Neural differentiation of rat adipose-derived stem cells in vitro. Cell Mol Neurobiol 32:1255–1263

    Article  CAS  PubMed  Google Scholar 

  • You D, Jang MJ, Lee J, Jeong IG, Kim HS, Moon KH, Suh N, Kim CS (2013) Periprostatic implantation of human bone marrow-derived mesenchymal stem cells potentiates recovery erectile function by intracavernosal injection in a rat model of cavernous nerve injury. Urology 81:104–110

    Article  PubMed  Google Scholar 

  • Zhang H, Yang R, Wang Z, Lin G, Lue TF, Lin CS (2011) Adipose tissue-derived stem cells secrete CXCL5 cytokine with neurotrophic effects on cavernous nerve regeneration. J Sex Med 8:437–446

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zuk PA (2010) The adipose-derived stem cell: looking back and looking ahead. Mol Biol Cell 21:1783–1787

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the grant from the National Natural Science Foundation of China (No. 81070483).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

    Chengcheng Ying, Wanli Hu, Xinmin Zheng & Xinghuan Wang

  2. Department of Anatomy and Embryology, School of Medicine, Wuhan University, Wuhan, China

    Bei Cheng

  3. Department of Endocrinology, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China

    Mei Yang

Authors
  1. Chengcheng Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanli Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xinmin Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xinghuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wanli Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ying, C., Hu, W., Cheng, B. et al. Erectile Function Restoration After Repair of Resected Cavernous Nerves by Adipose-Derived Stem Cells Combined with Autologous Vein Graft in Rats. Cell Mol Neurobiol 34, 393–402 (2014). https://doi.org/10.1007/s10571-013-0024-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-013-0024-7

Keywords

Search

Navigation