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Regenerative Medicine

Effects of transplantation of umbilical cord blood mononuclear cells into the scrotum on sexual function in elderly mice

    Jun Li

    Medical School, Ningde Normal University, Ningde, 352100, China

    Medical School, Kunming University, Kunming, 650214, China

    ,
    Yinghong Jiang

    *Author for correspondence:

    E-mail Address: yinghongjiang1@126.com

    Medical School, Kunming University, Kunming, 650214, China

    ,
    Wei Xue

    Medical School, Kunming University, Kunming, 650214, China

    ,
    Lejiang Liu

    Medical School, Kunming University, Kunming, 650214, China

    ,
    Hua Yu

    Medical School, Kunming University, Kunming, 650214, China

    ,
    Xuemei Zhang

    Medical School, Kunming University, Kunming, 650214, China

    ,
    Xiao Ye

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Jianrong Miao

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Jianling Liu

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Yueen Chen

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Xingbin Lan

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Xiaoqing Liu

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Wensong Yao

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Jianchuan Sun

    Medical School, Ningde Normal University, Ningde, 352100, China

    ,
    Jing Zheng

    Medical School, Ningde Normal University, Ningde, 352100, China

    &
    Jianzhong Xiao

    Medical School, Ningde Normal University, Ningde, 352100, China

    Published Online:https://doi.org/10.2217/rme-2022-0191

    Aim: This study investigated the effect of allografting umbilical cord blood mononuclear cells (UCBMCs) into the scrotum on sexual function in male elderly mice. Methods: UCBMCs were injected once into the scrotal sheath cavity of elderly mice. Results: The transplanted UCBMCs survived in the scrotal sheath cavity for 1 month. The mice had significantly increased blood testosterone concentrations, cyclic guanosine monophosphate (cGMP) levels and total nitric oxide synthase (T-NOS) activity in the corpus cavernosum and an increase in the number of mouse matings within 30 min (all p = 0.000). Conclusion: Scrotum-implanted UCBMCs improve the sexual function of male elderly mice through testosterone production and the NOS/cGMP pathway, which may provide an innovative transplantation approach for the treatment of erectile dysfunction.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Lin YC, Huang TJ, Yeh MH et al. Lung function impairment and cardiometabolic risks among rural adults: implication for an aging society. BMC Public Health 21, 960 (2021). https://doi.org/10.1186/s12889-021-10990-8
    • 2. Takatsuki S. Are we ready for the upcoming super-aging society? Circ. J. 85(8), 1263–1264 (2021).
    • 3. Zhou Y, Chen S, Zhang D et al. The efficacy and safety of acupuncture in the treatment of erectile dysfunction: a protocol for systematic review and meta-analysis. Medicine (Baltimore) 100, e25892 (2021).
    • 4. Burnett AL, Nehra A, Breau RH et al. Erectile dysfunction: AUA guideline. J. Urol. 200, 633–641 (2018). https://doi.org/10.1016/j.juro.2018.05.004
    • 5. de Oliveira PS, Ziegelmann MJ. Low-intensity shock wave therapy for the treatment of vasculogenic erectile dysfunction: a narrative review of technical considerations and treatment outcomes. Transl. Androl. Urol. 10(6), 2617–2628 (2021).
    • 6. Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17(1), 11–22 (2015).
    • 7. Song YS, Lee HJ, Park IH et al. Human neural crest stem cells transplanted in rat penile corpus cavernosum to repair erectile dysfunction. BJU Int. 102, 220–224 (2008).
    • 8. Nolazco G, Kovanecz I, Vernet D et al. Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat. BJU Int. 101, 1156–1164 (2008).
    • 9. Gur S, Kadowitz PJ, Hellstrom WJ. A review of current progress in gene and stem cell therapy for erectile dysfunction. Expert Opin. Biol. Ther. 8, 1521–1538 (2008).
    • 10. Albayrak O, Sener TE, Ersahin M et al. Mesenchymal stem cell therapy improves erectile dysfunction in experimental spinal cord injury. Int. J. Impot. Res. 32(3), 308–316 (2019).
    • 11. Bivalacqua TJ, Deng W, Kendirci M et al. 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(3), H1278–1290 (2007).
    • 12. Liu Y, Zhao S, Luo L et al. Mesenchymal stem cell-derived exosomes ameliorate erection by reducing oxidative stress damage of corpus cavernosum in a rat model of artery injury. J. Cell. Mol. Med. 23(11), 7462–7473 (2019).
    • 13. Al Demour S, Jafar H, Adwan S et al. Safety and potential therapeutic effect of two intracavernous autologous bone marrow derived mesenchymal stem cells injections in diabetic patients with erectile dysfunction: an open label phase I clinical trial. Urol. Int. 101, 358–365 (2018).
    • 14. Hutton JF, Gargett T, Sadlon TJ et al. Development of CD4 + CD25 + FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells. J. Leukoc. Biol. 85, 445–451 (2009).
    • 15. Bachstetter AD, Pabon MM, Cole MJ et al. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain. BMC Neurosci. 9, 22 (2008). https://doi.org/10.1186/1471-2202-9-22
    • 16. Li J, Mao Q, He J et al. Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem Cell Res. Ther. 8(1), 55 (2017).
    • 17. Nguyen Thanh L, Dam PTM, Nguyen HP et al. Can autologous adipose-derived mesenchymal stem cell transplantation improve sexual function in people with sexual functional deficiency? Stem Cell Rev. Rep. 17(6), 2153–2163 (2021). •• Autologous mesenchymal stem cells infusion is a potential therapeutic option for male patients with reduced sexual activity.
    • 18. Oztekin CV, Yilmaz-Oral D, Kaya-Sezginer E et al. Beneficial effects of human umbilical cord blood mononuclear cells on persistent erectile dysfunction after treatment of 5-alpha reductase inhibitor in rats. J. Sex. Med. 18, 889–899 (2021). https://doi.org/10.1016/j.jsxm.2021.02.005
    • 19. Bahk JY, Jung JH, Han H et al. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp. Clin. Transplant. 8, 150–160 (2010). • Creates the basis for the study described in the authors' article.
    • 20. Schulz TC, Young HY, Agulnick AD et al. A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS ONE 7, e37004 (2012).
    • 21. Neves J, Sousa-Victor P, Jasper H. Rejuvenating strategies for stem cell-based therapies in aging. Cell Stem Cell 20(2), 161–175 (2017).
    • 22. Kamelska-Sadowska AM, Wojtkiewicz J, Kowalski IM. Review of the current knowledge on the role of stem cell transplantation in neurorehabilitation. Biomed Res. Int. 2019, 3290894 (2019). https://doi.org/10.1155/2019/3290894 • Implants of exogenous neural stem cells may promote regeneration in aging organisms through stimulation of endogenous neurogenesis.
    • 23. Li J, Chen H, Lv YB et al. Intraperitoneal injection of multiplacentas pooled cells treatment on a mouse model with aplastic anemia. Stem Cells Int. 2016, 3279793 (2016).
    • 24. Li J, Wei Y, Yan L et al. Multiplacenta derived stem cell/cytokine treatment increases survival time in a mouse model with radiation-induced bone marrow damage. Cytotechnology 68, 2677–2686 (2016).
    • 25. Zhao XH, Qiu JH, Cai WQ et al. Preparation of infertile male rabbits by local electron beam irradiation for intratesticular transplantation of autologous bone marrow stem cells. Acta Cir. Bras. 28, 148–153 (2013).
    • 26. Kajbafzadeh AM, Abbasioun R, Sabetkish N et al. In vivo human corpus cavernosum regeneration: fabrication of tissue-engineered corpus cavernosum in rat using the body as a natural bioreactor. Int. Urol. Nephrol. 49, 1193–1199 (2017).
    • 27. Li J, Jiang Y, Yu H et al. Effects of UCMSCs delivered through different transplantation approaches on acute radiation enteritis in rats. Cell Transplant. 30, 9636897211025230 (2021). https://doi.org/10.1177/09636897211025230 • The scrotum is a continuation of the abdominal cavity. The study results indicated that umbilical cord mesenchymal stem cells with intraperitoneal injection approach are more likely to implant in the body.
    • 28. Huang SL, Huang WG, Xu HG et al. Establishment of a murine model for allogeneic umbilical cord blood transplantation. Zhongguo Shi Yan Xue Ye Xue Za Zhi 10(6), 564–567 (2002).
    • 29. Cai Y, Huang SL, Huang K et al. Comparison of efficacies of allogeneic hematopoietic stem cell transplantations between different routes of administration in mice. Zhongguo Shi Yan Xue Ye Xue Za Zhi 15(5), 998–1004 (2007).
    • 30. Zhang Y, Zhou F, Ge F. Effects of combined extracts of Lepidium meyenii and Allium tuberosum Rottl. on erectile dysfunction. BMC Complement. Altern. Med. 19, 135 (2019).
    • 31. Ratnasooriya WD, Wadsworth RM. Impairment of fertility of male rats with prazosin. Contraception 41(4), 441–447 (1990).
    • 32. Yoshimura H, Kimura N, Sugiura K. Preventive effects of various ginseng saponins on the development of copulatory disorder induced by prolonged individual housing in male mice. Methods Find. Exp. Clin. Pharmacol. 20(1), 59–64 (1998).
    • 33. Wang XY, Zhang JT. Effect of Ginsenoside Rb1 on mouse sexual function and its mechanism. Acta Pharmaceutica Sinica 35(7), 492–495 (2000).
    • 34. Priviero F, Calmasini F, Dela Justina V et al. Macrophage-specific Toll like receptor 9 (TLR9) causes corpus cavernosum dysfunction in mice fed a high fat diet. J. Sex. Med. 18(4), 723–731 (2021).
    • 35. Piao S, Kim IG, Lee JY et al. Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury. J. Sex. Med. 9(8), 1968–1979 (2012).
    • 36. Wang X, Chu S, Qian T et al. Ginsenoside Rg1 improves male copulatory behavior via NO/cGMP pathway. J. Sex. Med. 7, 743–750 (2010).
    • 37. Li D, Ren J, He L et al. Combined effects of oligopeptides isolated from Panax ginseng C.A. Meyer and Ostrea gigas Thunberg on sexual function in male mice. Int. J. Env. Res. Pub. He. 18, 2349 (2021).
    • 38. Hiremath DS, Priviero FBM, Webb RC et al. Constitutive LH receptor activity impairs NO-mediated penile smooth muscle relaxation. Reproduction 161, 31–41 (2021).
    • 39. Yu WM, Cheng F, Zhang XB et al. Buried penis decreases nitric oxide synthase of the corpus cavernosum. Zhonghua Nan Ke Xue 14(5), 411–413 (2008).
    • 40. Li J, Wang G, Qin W et al. Effect of aging on the endothelial function of the penile corpus cavernosum in rats. Zhonghua Nan Ke Xue 10(11), 824–826; 829 (2004).
    • 41. Zhang W, Wei Y, Cao X et al. Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production. J. Ethnopharmacol. 264, 113382 (2021). https://doi.org/10.1016/j.jep.2020.113382
    • 42. Qian C, Meng Q, Lu J et al. Human amnion mesenchymal stem cells restore spermatogenesis in mice with busulfan-induced testis toxicity by inhibiting apoptosis and oxidative stress. Stem Cell Res. Ther. 11, 290 (2020). https://doi.org/10.1186/s13287-020-01803-7
    • 43. Hassan AI, Alam SS. Evaluation of mesenchymal stem cells in treatment of infertility in male rats. Stem Cell Res. Ther. 5(6), 131 (2014).
    • 44. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol. Rev. 63, 811–859 (2011). https://doi.org/10.1124/pr.111.004515
    • 45. Qu X, Liu X, Cheng K et al. Mesenchymal stem cells inhibit Th17 cell differentiation by IL-10 secretion. Exp. Hematol. 40, 761–770 (2012). www.exphem.org/article/S0301-472X(12)00181-6/fulltext
    • 46. Li N, Sarojini H, An J et al. Prosaposin in the secretome of marrow stroma-derived neural progenitor cells protects neural cells from apoptotic death. J. Neurochem. 112, 1527–1538 (2010). https://doi.org/10.1111/j.1471-4159.2009.06565.x
    • 47. Estrada R, Li N, Sarojini H et al. Secretome from mesenchymal stem cells induces angiogenesis via Cyr61. J. Cell. Physiol. 219, 563–571 (2009). https://doi.org/10.1002/jcp.21701
    • 48. Wang P, Gao Q, Suo Z et al. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines. PLoS One 8, e57020 (2013).
    • 49. Kobayashi CI, Suda T. Regulation of reactive oxygen species in stem cells and cancer stem cells. J. Cell. Physiol. 227, 421–430 (2012).
    • 50. Shyh-Chang N, Daley GQ, Cantley LC. Stem cell metabolism in tissue development and aging. Development 140, 2535–2547 (2013).
    • 51. Falana BA, Oyeyipo IP. Selenium and zinc attenuate lead-induced reproductive toxicity in male sprague-dawley rats. Res. J. Med. Sci. 6, 66–70 (2012).
    • 52. Cai YT, Xiong CL, Shen SL et al. Mesenchymal stem cell-secreted factors delayed spermatogenesis injuries induced by busulfan involving intercellular adhesion molecule regulation. Andrologia 51(6), e13285 (2019). •• The results suggest mesenchymal stem cell-secreted factors protect spermatogenesis impairment.
    • 53. Hsiao CH, Ji AT, Chang CC et al. Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury. Stem Cell Res. Ther. 6(1), 113 (2015). •• Local injection of human mesenchymal stem cells into the testes of rats rescues torsion-induced infertility.
    • 54. Vahdati A, Fathi A, Hajihoseini M et al. The Regenerative effect of bone marrow-derived stem cells in spermatogenesis of infertile hamster. World J. Plast. Surgery 6, 18–25 (2017).
    • 55. Wang F, Liu C, Zhang SS et al. Transplantation of goat bone marrow mesenchymal stem cells (gMSCs) help restore spermatogenesis in endogenous germ cells-depleted mouse models. J. Integr. Agr. 12, 483–494 (2013). https://doi.org/10.1016/S2095-3119(13)60249-X
    • 56. Wang C, Cunningham G, Dobs A et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J. Clin. Endocr. Metab. 89(5), 2085–2098 (2004).
    • 57. Reilly CM, Stopper VS, Mills TM. Androgens modulate the alphaadrenergic responsiveness of vascular smooth muscle in the corpus cavernosum. J. Androl. 18(1), 26–31 (1997).
    • 58. Zvara P, Sioufi R, Schipper HM et al. Nitric oxide mediated erectile activity is a testosterone dependent event: a rat erection model. Int. J. Impot. Res. 7, 209–219 (1995).
    • 59. Lugg JA, Rajfer J, Gonzalez-Cadavid NF. Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology 136, 1495–1501 (1995).
    • 60. Penson DF, Ng C, Cai L et al. Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol. Reprod. 55, 567–574 (1996).
    • 61. Traish AM, Goldstein I, Kim NN. Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur. Urol. 52, 54–70 (2007).
    • 62. Marin R, Escrig A, Abreu P et al. Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol. Reprod. 61, 1012–1016 (1999).
    • 63. Park KH, Kim SW, Kim KD et al. Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum. BJU Int. 83, 327–333 (1999).
    • 64. Seo SI, Kim SW, Paick JS. The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat. Asian J. Androl. 1, 169–174 (1999).
    • 65. Li R, Meng X, Zhang Y et al. Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated rats. PeerJ 4, e2000 (2016).
    • 66. de Deus JL, Dagostin ALA, Varanda WA. Nitric oxide modulates ATP-evoked currents in mouse Leydig cells. Braz. J. Med. Biol. Res. 51, e6693 (2018).
    • 67. Goswami SK, Inamdar MN, Jamwal R et al. Effect of Cinnamomum cassia methanol extract and sildenafil on arginase and sexual function of young male Wistar rats. J. Sex. Med. 11, 1475–1483 (2014).
    • 68. Lagoda G, Muschamp JW, Vigdorchik A et al. A nitric oxide synthesis inhibitor in the medial preoptic area inhibits copulation and stimulus sensitization in male rats. Behav. Neurosci. 118, 1317–1323 (2004).
    • 69. Musicki B, Burnett AL. Mechanisms underlying priapism in sickle cell disease: targeting and key innovations on the preclinical landscape. Expert Opin. Ther. Tar. 24, 439–450 (2020).
    • 70. Henesy MB, Britain AL, Zhu B et al. Calcineurin regulates homologous desensitization of natriuretic peptide receptor-A and inhibits ANP-induced testosterone production in MA-10 cells. PLOS ONE 7, e41711 (2012).