Volume 14 Issue 3
May  2023
Turn off MathJax
Article Contents
Article Navigation >  ORGAN TRANSPLANTATION  > 2023  >  14(3): 319-326
Mo Jiahui, Li Xinyu, Chen Zhihong, et al. Current status and reflections on stem cell transplantation in the treatment of testicular aging[J]. ORGAN TRANSPLANTATION, 2023, 14(3): 319-326. doi: 10.3969/j.issn.1674-7445.2023.03.001
Citation: Mo Jiahui, Li Xinyu, Chen Zhihong, et al. Current status and reflections on stem cell transplantation in the treatment of testicular aging[J]. ORGAN TRANSPLANTATION, 2023, 14(3): 319-326. doi: 10.3969/j.issn.1674-7445.2023.03.001
shu

Current status and reflections on stem cell transplantation in the treatment of testicular aging

doi: 10.3969/j.issn.1674-7445.2023.03.001

  • Department of Urology and Andrology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

More Information
  • Corresponding author: Deng Chunhua, Email: dengchh@mail.sysu.edu.cn
  • Received Date: 2023-02-20
  • Publish Date: 2023-05-15
    Abstract
  • Testicular aging is mainly characterized by a gradual decline in the capability of testosterone synthesis and spermatogenesis, which not only affects male fertility, but also correlates with aging-related chronic diseases intimately. Therefore, delaying testicular aging plays a significant role in improving the health and quality of life of middle-aged and elderly men. Stem cells are a cell group with potent self-renewal capability and multi-directional differentiation potential. In recent years, the research of stem cells in basic and clinical application has been carried out in-depth, which has accelerated the development of cell therapy. Currently, stem cell transplantation has been employed to treat multiple diseases, which has captivated widespread attention in the field of aging and regenerative medicine. Stem cell transplantation has demonstrated promising prospects in the treatment of testicular aging. In this article, research profile and progress of stem cell transplantation in the treatment of testicular aging were reviewed, and bottleneck issues encountered in clinical translation and strategies for optimizing clinical efficacy were discussed, aiming to provide novel ideas for the research and development and clinical translation of stem cell therapy for testicular aging.

     

    • FullText(HTML)
  • loading
    • References(57)
  • [1]
    ZHANG J, WEI L, DENG X, et al. Current status and reflections on fertility preservation in China[J]. J Assist Reprod Genet, 2022, 39(12): 2835-2845. DOI: 10.1007/s10815-022-02648-0.
    [2]
    MATZKIN ME, CALANDRA RS, ROSSI SP, et al. Hallmarks of testicular aging: the challenge of anti-inflammatory and antioxidant therapies using natural and/or pharmacological compounds to improve the physiopathological status of the aged male gonad[J]. Cells, 2021, 10(11): 3114. DOI: 10.3390/cells10113114.
    [3]
    FRUNGIERI MB, CALANDRA RS, BARTKE A, et al. Male and female gonadal ageing: its impact on health span and life span[J]. Mech Ageing Dev, 2021, 197: 111519. DOI: 10.1016/j.mad.2021.111519.
    [4]
    李湘平, 邓春华. 男性生殖衰老特征的多角度认识[J]. 中山大学学报(医学科学版), 2022, 43(06): 871-877. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0601.

    LI XP, DENG CH. Male Reproductive aging characteristics: a multi-perspective understanding[J]. J Sun Yat-sen Univ (Med Sci), 2022, 43(06): 871-877. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0601.
    [5]
    KUES WA, KUMAR D, SELOKAR NL, et al. Applications of genome editing tools in stem cells towards regenerative medicine: an update[J]. Curr Stem Cell Res Ther, 2022, 17(3): 267-279. DOI: 10.2174/1574888X16666211124095527.
    [6]
    DE LUCA M, AIUTI A, COSSU G, et al. Advances in stem cell research and therapeutic development[J]. Nat Cell Biol, 2019, 21(7): 801-811. DOI: 10.1038/s41556-019-0344-z.
    [7]
    SAMADI P, SAKI S, MANOOCHEHRI H, et al. Therapeutic applications of mesenchymal stem cells: a comprehensive review[J]. Curr Stem Cell Res Ther, 2021, 16(3): 323-353. DOI: 10.2174/1574888X15666200914142709.
    [8]
    WENG Z, WANG Y, OUCHI T, et al. Mesenchymal stem/stromal cell senescence: hallmarks, mechanisms, and combating strategies[J]. Stem Cells Transl Med, 2022, 11(4): 356-371. DOI: 10.1093/stcltm/szac004.
    [9]
    GUL M, HILDORF S, DONG L, et al. Review of injection techniques for spermatogonial stem cell transplantation[J]. Hum Reprod Update, 2020, 26(3): 368-391. DOI: 10.1093/humupd/dmaa003.
    [10]
    EYNI H, GHORBANI S, NAZARI H, et al. Advanced bioengineering of male germ stem cells to preserve fertility[J]. J Tissue Eng, 2021, 12: 20417314211060590. DOI: 10.1177/20417314211060590.
    [11]
    IOACHIMESCU AG. Updates in male hypogonadism[J]. Endocrinol Metab Clin North Am, 2022, 51(1): xiii-xiv. DOI: 10.1016/j.ecl.2021.12.001.
    [12]
    SALVIO G, CIARLONI A, CUTINI M, et al. Metabolic syndrome and male fertility: beyond heart consequences of a complex cardiometabolic endocrinopathy[J]. Int J Mol Sci, 2022, 23(10): 5497. DOI: 10.3390/ijms23105497.
    [13]
    LEE TH, KIM DS, KIM DK, et al. Effect of male age on reproductive function: a comparison of young and middle-aged men[J]. Investig Clin Urol, 2023, 64(1): 51-55. DOI: 10.4111/icu.20220302.
    [14]
    JANECZKO D, HOŁOWCZUK M, ORZEŁ A, et al. Paternal age is affected by genetic abnormalities, perinatal complications and mental health of the offspring[J]. Biomed Rep, 2020, 12(3): 83-88. DOI: 10.3892/br.2019.1266.
    [15]
    TSAMETIS CP, ISIDORI AM. Testosterone replacement therapy: for whom, when and how?[J]. Metabolism, 2018, 86: 69-78. DOI: 10.1016/j.metabol.2018.03.007.
    [16]
    TWITCHELL DK, PASTUSZAK AW, KHERA M. Controversies in testosterone therapy[J]. Sex Med Rev, 2021, 9(1): 149-159. DOI: 10.1016/j.sxmr.2020.09.004.
    [17]
    CHONG YH, PANKHURST MW, MCLENNAN IS. The testicular hormones AMH, InhB, INSL3, and testosterone can be independently deficient in older men[J]. J Gerontol A Biol Sci Med Sci, 2017, 72(4): 548-553. DOI: 10.1093/gerona/glw143.
    [18]
    RODRIGUES DOS SANTOS M, BHASIN S. Benefits and risks of testosterone treatment in men with age-related decline in testosterone[J]. Annu Rev Med, 2021, 72: 75-91. DOI: 10.1146/annurev-med-050219-034711.
    [19]
    LEVIT GS, HOSSFELD U. Ernst Haeckel in the history of biology[J]. Curr Biol, 2019, 29(24): R1276-R1284. DOI: 10.1016/j.cub.2019.10.064.
    [20]
    LIU G, DAVID BT, TRAWCZYNSKI M, et al. Advances in pluripotent stem cells: history, mechanisms, technologies, and applications[J]. Stem Cell Rev Rep, 2020, 16(1): 3-32. DOI: 10.1007/s12015-019-09935-x.
    [21]
    DING L, YAN G, WANG B, et al. Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility[J]. Sci China Life Sci, 2018, 61(12): 1554-1565. DOI: 10.1007/s11427-017-9272-2.
    [22]
    DIAO L, TUREK PJ, JOHN CM, et al. Roles of spermatogonial stem cells in spermatogenesis and fertility restoration[J]. Front Endocrinol (Lausanne), 2022, 13: 895528. DOI: 10.3389/fendo.2022.895528.
    [23]
    BRINSTER RL, AVARBOCK MR. Germline transmission of donor haplotype following spermatogonial transplantation[J]. Proc Natl Acad Sci U S A, 1994, 91(24): 11303-11307. DOI: 10.1073/pnas.91.24.11303.
    [24]
    HERMANN BP, SUKHWANI M, WINKLER F, et al. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm[J]. Cell Stem Cell, 2012, 11(5): 715-726. DOI: 10.1016/j.stem.2012.07.017.
    [25]
    SANOU I, VAN MAAREN J, ELIVELD J, et al. Spermatogonial stem cell-based therapies: taking preclinical research to the next level[J]. Front Endocrinol (Lausanne), 2022, 13: 850219. DOI: 10.3389/fendo.2022.850219.
    [26]
    CHEN P, ZIRKIN BR, CHEN H. Stem Leydig cells in the adult testis: characterization, regulation and potential applications[J]. Endocr Rev, 2020, 41(1): 22-32. DOI: 10.1210/endrev/bnz013.
    [27]
    SANTIAGO J, SILVA JV, ALVES MG, et al. Testicular aging: an overview of ultrastructural, cellular, and molecular alterations[J]. J Gerontol A Biol Sci Med Sci, 2019, 74(6): 860-871. DOI: 10.1093/gerona/gly082.
    [28]
    GE RS, DONG Q, SOTTAS CM, et al. In search of rat stem Leydig cells: identification, isolation, and lineage-specific development[J]. Proc Natl Acad Sci U S A, 2006, 103(8): 2719-2724. DOI: 10.1073/pnas.0507692103.
    [29]
    KUANG S, HE F, LIU G, et al. CCR2-engineered mesenchymal stromal cells accelerate diabetic wound healing by restoring immunological homeostasis[J]. Biomaterials, 2021, 275: 120963. DOI: 10.1016/j.biomaterials.2021.120963.
    [30]
    AITKEN RJ, BAKER MA. Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development[J]. Int J Dev Biol, 2013, 57(2/3/4): 265-272. DOI: 10.1387/ijdb.130146ja.
    [31]
    HSIAO CH, JI AT, CHANG CC, et al. Local injection of mesenchymal stem cells protects testicular torsion-induced germ cell injury[J]. Stem Cell Res Ther, 2015, 6(1): 113. DOI: 10.1186/s13287-015-0079-0.
    [32]
    SHERIF IO, SABRY D, ABDEL-AZIZ A, et al. The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity[J]. Stem Cell Res Ther, 2018, 9(1): 196. DOI: 10.1186/s13287-018-0946-6.
    [33]
    GE RS, LI X, WANG Y. Leydig cell and spermatogenesis[J]. Adv Exp Med Biol, 2021, 1288: 111-129. DOI: 10.1007/978-3-030-77779-1_6.
    [34]
    LI L, PAPADOPOULOS V. Advances in stem cell research for the treatment of primary hypogonadism[J]. Nat Rev Urol, 2021, 18(8): 487-507. DOI: 10.1038/s41585-021-00480-2.
    [35]
    LO KC, LEI Z, RAO CHV, et al. De novo testosterone production in luteinizing hormone receptor knockout mice after transplantation of Leydig stem cells[J]. Endocrinology, 2004, 145(9): 4011-4015. DOI: 10.1210/en.2003-1729.
    [36]
    ZANG ZJ, WANG J, CHEN Z, et al Transplantation of CD51+ stem Leydig cells: a new strategy for the treatment of testosterone deficiency[J]. Stem Cells, 2017, 35(5): 1222-1232. DOI: 10.1002/stem.2569.
    [37]
    JIANG MH, CAI B, TUO Y, et al. Characterization of nestin-positive stem Leydig cells as a potential source for the treatment of testicular Leydig cell dysfunction[J]. Cell Res, 2014, 24(12): 1466-1485. DOI: 10.1038/cr.2014.149.
    [38]
    ZHANG M, WANG J, DENG C, et al. Transplanted human p75-positive stem Leydig cells replace disrupted Leydig cells for testosterone production[J]. Cell Death Dis, 2017, 8(10): e3123. DOI: 10.1038/cddis.2017.531.
    [39]
    XIA K, MA Y, FENG X, et al. Endosialin defines human stem Leydig cells with regenerative potential[J]. Hum Reprod, 2020, 35(10): 2197-2212. DOI: 10.1093/humrep/deaa174.
    [40]
    XIA K, CHEN H, WANG J, et al. Restorative functions of autologous stem Leydig cell transplantation in a testosterone-deficient non-human primate model[J]. Theranostics, 2020, 10(19): 8705-8720. DOI: 10.7150/thno.46854.
    [41]
    ALFANO M, TASCINI AS, PEDERZOLI F, et al. Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia[J]. Nat Commun, 2021, 12(1): 5205. DOI: 10.1038/s41467-021-25544-0.
    [42]
    YAZAWA T, MIZUTANI T, YAMADA K, et al. Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells[J]. Endocrinology, 2006, 147(9): 4104-4111. DOI: 10.1210/en.2006-0162.
    [43]
    HOU L, DONG Q, WU YJ, et al. Gonadotropins facilitate potential differentiation of human bone marrow mesenchymal stem cells into Leydig cells in vitro[J]. Kaohsiung J Med Sci, 2016, 32(1): 1-9. DOI: 10.1016/j.kjms.2015.10.008.
    [44]
    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?[J]. Stem Cell Rev Rep, 2021, 17(6): 2153-2163. DOI: 10.1007/s12015-021-10196-w.
    [45]
    LI L, LI Y, SOTTAS C, et al. Directing differentiation of human induced pluripotent stem cells toward androgen-producing Leydig cells rather than adrenal cells[J]. Proc Natl Acad Sci U S A, 2019, 116(46): 23274-23283. DOI: 10.1073/pnas.1908207116.
    [46]
    CHEN X, LI C, CHEN Y, et al. Differentiation of human induced pluripotent stem cells into Leydig-like cells with molecular compounds[J]. Cell Death Dis, 2019, 10(3): 220. DOI: 10.1038/s41419-019-1461-0.
    [47]
    ZHAO X, WAN W, ZHANG X, et al. Spermatogonial stem cell transplantation in large animals[J]. Animals (Basel), 2021, 11(4): 918. DOI: 10.3390/ani11040918.
    [48]
    KADAM P, NTEMOU E, BAERT Y, et al. Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice[J]. Stem Cell Res Ther, 2018, 9(1): 317. DOI: 10.1186/s13287-018-1065-0.
    [49]
    LI X, TIAN E, WANG Y, et al. Stem Leydig cells: current research and future prospects of regenerative medicine of male reproductive health[J]. Semin Cell Dev Biol, 2022, 121: 63-70. DOI: 10.1016/j.semcdb.2021.05.007.
    [50]
    MOEINABADI-BIDGOLI K, BABAJANI A, YAZDANPANAH G, et al. Translational insights into stem cell preconditioning: from molecular mechanisms to preclinical applications[J]. Biomed Pharmacother, 2021, 142: 112026. DOI: 10.1016/j.biopha.2021.112026.
    [51]
    HUANG ML, MICHALAK AL, FISHER CJ, et al. Small molecule antagonist of cell surface glycosaminoglycans restricts mouse embryonic stem cells in a pluripotent state[J]. Stem Cells, 2018, 36(1): 45-54. DOI: 10.1002/stem.2714.
    [52]
    LIU H, ZHU X, CAO X, et al. IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate chronic prostatitis/chronic pelvic pain syndrome through systemic immunity[J]. Stem Cell Res Ther, 2021, 12(1): 514. DOI: 10.1186/s13287-021-02579-0.
    [53]
    KARPOVA T, RAVICHANDIRAN K, INSISIENMAY L, et al. Steroidogenic factor 1 differentially regulates fetal and adult Leydig cell development in male mice[J]. Biol Reprod, 2015, 93(4): 83. DOI: 10.1095/biolreprod.115.131193.
    [54]
    SHEN YC, SHAMI AN, MORITZ L, et al. TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice[J]. Nat Commun, 2021, 12(1): 3876. DOI: 10.1038/s41467-021-24130-8.
    [55]
    PIPREK RP, KOLASA M, PODKOWA D, et al. Transcriptional profiling validates involvement of extracellular matrix and proteinases genes in mouse gonad development[J]. Mech Dev, 2018, 149: 9-19. DOI: 10.1016/j.mod.2017.11.001.
    [56]
    KHAYAMBASHI P, IYER J, PILLAI S, et al. Hydrogel encapsulation of mesenchymal stem cells and their derived exosomes for tissue engineering[J]. Int J Mol Sci, 2021, 22(2): 684. DOI: 10.3390/ijms22020684.
    [57]
    BAERT Y, DE KOCK J, ALVES-LOPES JP, et al. Primary human testicular cells self-organize into organoids with testicular properties[J]. Stem Cell Reports, 2017, 8(1): 30-38. DOI: 10.1016/j.stemcr.2016.11.012.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(2)  / Tables(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (1026) PDF downloads(85) Cited by()
    Proportional views
    Related

    WeChat Subscription Account

    Wechat Service Account

    Contact Us
    • Tel：020-38736410
    • Email: organtranspl@163.com
    • Address：The Third Affiliated Hospital of Sun Yat-sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou
    • Editorial Office of Organ Transplantation  粤ICP备2021030844号
    Links

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return