Skip to content
2000
image of Insights into Endometriosis Organoids Based on Uterine Tissue Engineering: A Mini-review

Abstract

Endometriosis is a chronic condition where tissue similar to the endometrium grows outside the uterus, affecting 5-10% of women and causing pelvic pain, painful periods, and infertility. Diseases of the endometrium, the lining of the uterus, can lead to a variety of reproductive health issues, including infertility, irregular bleeding, and endometrial cancer. Researchers have developed advanced systems using uterine organoids and decellularized tissue scaffolds to understand and model these diseases. The main limitations of traditional 2D monolayer cultures include reduced biological activity, reduced hormone responsiveness, and lack of interaction with ECM. Researchers have investigated 3D culture approaches to address these shortcomings, such as scaffold-free organoids and decellularized tissue scaffolds. Organoid systems can better recapitulate the cellular heterogeneity and physiological functions of the native endometrium. Decellularization protocols have been optimized to generate intact uterine scaffolds that preserve the structural and compositional features of the ECM. Implantation of these bioscaffolds into animal models demonstrated their biocompatibility and regenerative potential. Further refinements of organoid and scaffold technologies, including chemically defined matrices and organ-on-a-chip platforms, will improve our ability to model the uterus. Integration of these advanced models with patient-derived cells will enable personalized disease modeling and the development of targeted therapies. The combination of organoids, decellularized scaffolds, and microfluidic technologies holds great potential for exploring reproductive biology, drug screening, and developing regenerative therapies for uterine diseases and infertility.

Loading

Article metrics loading...

/content/journals/cscr/10.2174/011574888X360426250529055140
2025-06-05
2025-09-15
Loading full text...

Full text loading...

References

  1. Parasar P. Ozcan P. Terry K.L. Endometriosis: Epidemiology, diagnosis and clinical management. Curr. Obstet. Gynecol. Rep. 2017 6 1 34 41 10.1007/s13669‑017‑0187‑1 29276652
    [Google Scholar]
  2. Wu J. Lin S. Kong S. Psychological stress and functional endometrial disorders: Update of mechanism insights. Front. Endocrinol. (Lausanne) 2021 12 690255 10.3389/fendo.2021.690255 34413829
    [Google Scholar]
  3. Nijkang N.P. Anderson L. Markham R. Manconi F. Endometrial polyps: Pathogenesis, sequelae and treatment. SAGE Open Med. 2019 7 2050312119848247 10.1177/2050312119848247 31105939
    [Google Scholar]
  4. Ring K.L. Mills A.M. Modesitt S.C. Endometrial hyperplasia. Obstet. Gynecol. 2022 140 6 1061 1075 [PMID: 36357974
    [Google Scholar]
  5. Mills A.M. Longacre T.A. Endometrial hyperplasia Seminars in Diagnostic Pathology. Elsevier 2010
    [Google Scholar]
  6. Morice P. Leary A. Creutzberg C. Abu-Rustum N. Darai E. Endometrial cancer. Lancet 2016 387 10023 1094 1108 10.1016/S0140‑6736(15)00130‑0 26354523
    [Google Scholar]
  7. Ikhena D.E. Bulun S.E. Literature review on the role of uterine fibroids in endometrial function. Reprod. Sci. 2018 25 5 635 643 10.1177/1933719117725827 28826369
    [Google Scholar]
  8. Sommers S.C. Defining the pathology of endometrial hyperplasia, dysplasia and carcinoma. Pathol. Res. Pract. 1982 174 3 175 197 10.1016/S0344‑0338(82)80066‑6 6292884
    [Google Scholar]
  9. Stringfellow H.F. Elliot V.J. Endometrial metaplasia. Diagn. Histopathol. 2017 23 7 303 310 10.1016/j.mpdhp.2017.05.006
    [Google Scholar]
  10. Rafique S. Decherney A.H. Medical management of endometriosis. Clin. Obstet. Gynecol. 2017 60 3 485 496 10.1097/GRF.0000000000000292 28590310
    [Google Scholar]
  11. Filby C.E. Wyatt K.A. Mortlock S. Comparison of organoids from menstrual fluid and hormone-treated endometrium: Novel tools for gynecological research. J. Pers. Med. 2021 11 12 1314 10.3390/jpm11121314 34945786
    [Google Scholar]
  12. Kovina M.V. Krasheninnikov M.E. Dyuzheva T.G. Human endometrial stem cells: High-yield isolation and characterization. Cytotherapy 2018 20 3 361 374 10.1016/j.jcyt.2017.12.012 29397307
    [Google Scholar]
  13. Wang F. Qualls A.E. Marques-Fernandez L. Colucci F. Biology and pathology of the uterine microenvironment and its natural killer cells. Cell. Mol. Immunol. 2021 18 9 2101 2113 10.1038/s41423‑021‑00739‑z 34426671
    [Google Scholar]
  14. Cousins F.L. Pandoy R. Jin S. Gargett C.E. The elusive endometrial epithelial stem/progenitor cells. Front. Cell Dev. Biol. 2021 9 640319 10.3389/fcell.2021.640319 33898428
    [Google Scholar]
  15. Liu M. Ji M. Cheng J. Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution. Nat. Commun. 2023 14 1 7356 10.1038/s41467‑023‑43102‑8 37963860
    [Google Scholar]
  16. Arnold J.T. Kaufman D.G. Seppälä M. Lessey B.A. Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model. Hum. Reprod. 2001 16 5 836 845 10.1093/humrep/16.5.836 11331626
    [Google Scholar]
  17. Gargett C.E. Uterine stem cells: What is the evidence? Hum. Reprod. Update 2007 13 1 87 101 10.1093/humupd/dml045 16960017
    [Google Scholar]
  18. Schutte S.C. Taylor R.N. A tissue-engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization, and menstruation. Fertil. Steril. 2012 97 4 997 1003 10.1016/j.fertnstert.2012.01.098 22306710
    [Google Scholar]
  19. Shved N. Egorova A. Osinovskaya N. Kiselev A. Development of primary monolayer cell model and organotypic model of uterine leiomyoma. Methods Protoc. 2022 5 1 16 10.3390/mps5010016 35200532
    [Google Scholar]
  20. Chitcholtan K. Asselin E. Parent S. Sykes P.H. Evans J.J. Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Exp. Cell Res. 2013 319 1 75 87 10.1016/j.yexcr.2012.09.012 23022396
    [Google Scholar]
  21. Xu J. Zhang L. Ye Z. A 3D “sandwich” co-culture system with vascular niche supports mouse embryo development from E3.5 to E7.5 in vitro. Stem Cell Res. Ther. 2023 14 1 349 10.1186/s13287‑023‑03583‑2 38072932
    [Google Scholar]
  22. Cheng Y.H. Huang C.W. Lien H.T. A preliminary investigation of the roles of endometrial cells in endometriosis development via in vitro and in vivo analyses. Int. J. Mol. Sci. 2024 25 7 3873 10.3390/ijms25073873 38612685
    [Google Scholar]
  23. Muruganandan S. Fan X. Dhal S. Nayak N.R. Development of a 3D tissue slice culture model for the study of human endometrial repair and regeneration. Biomolecules 2020 10 1 136 10.3390/biom10010136 31947662
    [Google Scholar]
  24. Hellström M. El-Akouri R.R. Sihlbom C. Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization. Acta Biomater. 2014 10 12 5034 5042 10.1016/j.actbio.2014.08.018 25169258
    [Google Scholar]
  25. Sehic E. de Miguel Gómez L. Rabe H. Transplantation of a bioengineered tissue patch promotes uterine repair in the sheep. Biomater. Sci. 2024 12 8 2136 2148 10.1039/D3BM01912H 38482883
    [Google Scholar]
  26. Daryabari S.S. Fendereski K. Ghorbani F. Whole-organ decellularization of the human uterus and in vivo application of the bio-scaffolds in animal models. J. Assist. Reprod. Genet. 2022 39 6 1237 1247 10.1007/s10815‑022‑02492‑2 35513746
    [Google Scholar]
  27. Wiwatpanit T. Murphy A.R. Lu Z. Scaffold-free endometrial organoids respond to excess androgens associated with polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 2020 105 3 769 780 10.1210/clinem/dgz100 31614364
    [Google Scholar]
  28. Li W-X. Liang G-T. Yan W. Artificial uterus on a microfluidic chip. Chin. J. Anal. Chem. 2013 41 4 467 472 10.1016/S1872‑2040(13)60639‑8
    [Google Scholar]
  29. Xiao S. Coppeta J.R. Rogers H.B. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat. Commun. 2017 8 1 14584 10.1038/ncomms14584 28350383
    [Google Scholar]
  30. Young R.E. Huh D.D. Organ-on-a-chip technology for the study of the female reproductive system. Adv. Drug Deliv. Rev. 2021 173 461 478 10.1016/j.addr.2021.03.010 33831478
    [Google Scholar]
  31. Li Y. Tang P. Cai S. Peng J. Hua G. Organoid based personalized medicine: from bench to bedside. Cell Regen. (Lond.) 2020 9 1 21 10.1186/s13619‑020‑00059‑z 33135109
    [Google Scholar]
  32. Heidari-Khoei H. Esfandiari F. Hajari M.A. Ghorbaninejad Z. Piryaei A. Baharvand H. Organoid technology in female reproductive biomedicine. Reprod. Biol. Endocrinol. 2020 18 1 64 10.1186/s12958‑020‑00621‑z 32552764
    [Google Scholar]
  33. Arjmand B. Rabbani Z. Soveyzi F. Advancement of organoid technology in regenerative medicine. Regen. Eng. Transl. Med. 2023 9 1 83 96 10.1007/s40883‑022‑00271‑0 35968268
    [Google Scholar]
  34. Yang S. Hu H. Kung H. Organoids: The current status and biomedical applications. MedComm 2023 4 3 e274 10.1002/mco2.274 37215622
    [Google Scholar]
  35. Alzamil L. Nikolakopoulou K. Turco M.Y. Organoid systems to study the human female reproductive tract and pregnancy. Cell Death Differ. 2021 28 1 35 51 10.1038/s41418‑020‑0565‑5 32494027
    [Google Scholar]
  36. Rawlings T.M. Makwana K. Tryfonos M. Lucas E.S. Organoids to model the endometrium: Implantation and beyond. Reprod Fertility 2021 2 3 R85 R101 10.1530/RAF‑21‑0023 35118399
    [Google Scholar]
  37. Chumduri C. Turco M.Y. Organoids of the female reproductive tract. J. Mol. Med. (Berl.) 2021 99 4 531 553 10.1007/s00109‑020‑02028‑0 33580825
    [Google Scholar]
  38. Gu Z.Y. Jia S.Z. Liu S. Leng J.H. Endometrial organoids: A new model for the research of endometrial-related diseases. Biol. Reprod. 2020 103 5 918 926 10.1093/biolre/ioaa124 32697306
    [Google Scholar]
/content/journals/cscr/10.2174/011574888X360426250529055140
Loading
/content/journals/cscr/10.2174/011574888X360426250529055140
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: ondometer ; Endometriosis ; tissue engineering ; cell culture ; uterus ; organoid
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test