Yağ doku kaynaklı mezenkimal kök hücrelerin ve koşullu besiyerinin deneysel prematür over yetmezliği modeli üzerine etkileri
Öz
Amaç: Kemoterapi kaynaklı prematür over yetmezliği (POY) tedavisi için önerilebilecek yağ doku mezenkimal kök hücreleri (YDMKH) ve bu hücrelerden elde edilmiş koşullu besiyerinin (KB) oksidatif stres ve apoptoz üzerine etkilerinin araştırılması amaçlandı.
Gereç ve Yöntem: Çalışmada Wistar albino cinsi erişkin dişi sıçanlar 4 gruba ayrıldı. Kontrol, POY, POY+YDMKH, POY+KB. Ovaryumda histopatolojik değerlendirmeler için H&E boyamaları yapıldı ve tüm ovaryum folilkülleri sayıldı. Oksidatif stres ve apoptoz belirteci olarak iNOS ve Caspase3 ekspresyonları immunohistokimyasal olarak gösterildi.
Bulgular: Analizler sonucu POY grubu ovaryumlarında foliküller hücre dejenerasyonları, vakuolizasyon, gibi dejenerasyonlar gözlenirken, YDMKH ve KB gruplarında bu dejenerasyonlarda anlamlı azalmalar görüldü. POY grubunda artmış olan iNOS ve Caspase3 ekspresyonları YDMKH ve KB gruplarının her ikisinde de istatistiksel olarak anlamlı şekilde azaldı.
Sonuç: Rejeneratif tıp alanında her geçen gün kullanımı artan mezenkimal kök hücrelerin ve hücresiz koşullu besiyerinin prematür over yetmezliğinde hastalığın temel mekanizmalarından olan apoptoz ve oksidatif stresin azaltılması yoluyla, POY için alternatif bir tedavi stratejisi olabileceği gösterildi.
Anahtar Kelimeler
prematür over yetmezliği mezenkimal kök hücre koşullu besiyeri apoptoz oksidatif stres
Destekleyen Kurum
Manisa Celal Bayar Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi
Proje Numarası
2019-021
Teşekkür
Bu çalışma, Manisa Celal Bayar Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından 2019-021 numaralı proje ile desteklenmiştir
Kaynakça
- 1. Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, van Wijnen AJ, Cool SM. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem cells translational medicine. 2017;6(12):2173-2185.
- 2. Esfandyari S, Chugh RM, Park H-s, Hobeika E, Ulin M, Al-Hendy A. Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility. Cells. 2020;9(10):2253.
- 3. Fazeli Z, Abedindo A, Omrani MD, Ghaderian SMH. Mesenchymal stem cells (MSCs) therapy for recovery of fertility: a systematic review. Stem Cell Reviews and Reports. 2018;14(1):1-12.
- 4. Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfusion Medicine and Hemotherapy. 2016;43(4):268-274.
- 5. Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15(6):641-648.
- 6. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends in biotechnology. 2006;24(4):150-154.
- 7. Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circulation research. 2007;100(9):1249-1260.
- 8. Zhu Y, Liu T, Song K, Fan X, Ma X, Cui Z. Adipose‐derived stem cell: a better stem cell than BMSC. Cell Biochemistry and Function: Cellular biochemistry and its modulation by active agents or disease. 2008;26(6):664-675.
- 9. Sun M, Wang S, Li Y, et al. Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure. Stem cell research & therapy. 2013;4(4):80.
- 10. Bogatcheva N, Coleman M. Conditioned Medium of Mesenchymal Stromal Cells: A New Class of Therapeutics. Biochemistry (Moscow). 2019;84(11):1375-1389.
- 11. Kim HO, Choi S-M, Kim H-S. Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders. Tissue Engineering and Regenerative Medicine. 2013;10(3):93-101.
- 12. Park B-S, Kim W-S, Choi J-S, et al. Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion. Biomedical Research. 2010;31(1):27-34.
- 13. Di Santo S, Yang Z, von Ballmoos MW, et al. Novel cell-free strategy for therapeutic angiogenesis: in vitro generated conditioned medium can replace progenitor cell transplantation. PLoS One. 2009;4(5):e5643.
- 14. Mirabella T, Cilli M, Carlone S, Cancedda R, Gentili C. Amniotic liquid derived stem cells as reservoir of secreted angiogenic factors capable of stimulating neo-arteriogenesis in an ischemic model. Biomaterials. 2011;32(15):3689-3699.
- 15. Mishra PJ, Mishra PJ, Banerjee D. Cell-free derivatives from mesenchymal stem cells are effective in wound therapy. World Journal of Stem Cells. 2012;4(5):35.
- 16. ESHRE. Management of women with premature ovarian insufficiency, 2015.
- 17. Santoro NF, Cooper AR. Primary Ovarian Insufficiency: a Clinical Guide to Early Menopause: Springer, 2016.
- 18. Shelling AN. Premature ovarian failure. Reproduction. 2010.
- 19. Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Human reproduction update. 2001;7(6):535-543.
- 20. Byrne J, Fears TR, Gail MH, et al. Early menopause in long-term survivors of cancer during adolescence. American Journal of Obstetrics & Gynecology. 1992;166(3):788-793.
- 21. Hao X, Anastácio A, Liu K, Rodriguez-Wallberg KA. Ovarian Follicle Depletion Induced by Chemotherapy and the Investigational Stages of Potential Fertility-Protective Treatments-A Review. International journal of molecular sciences. 2019;20(19):4720.
- 22. Jeelani R, Khan SN, Shaeib F, et al. Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality. Free Radical Biology and Medicine. 2017;110:11-18.
- 23. Szymanska KJ, Tan X, Oktay K. Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging. Molecular Human Reproduction. 2020;26(8):553-566.
- 24. Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertility and sterility. 2016;106(7):1588-1599.
- 25. Chen L, Guo S, Wei C, Li H, Wang H, Xu Y. Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report. Experimental and therapeutic medicine. 2018;15(5):4105-4118.
- 26. Kasap B, Kasap Ş, Vatansever S, et al. Effects of adipose and bone marrow-derived mesenchymal stem cells on vaginal atrophy in a rat menopause model. Gene. 2019;711:143937.
- 27. Brini AT, Amodeo G, Ferreira LM, et al. Therapeutic effect of human adipose-derived stem cells and their secretome in experimental diabetic pain. Scientific Reports. 2017;7(1):9904.
- 28. Ntege EH, Sunami H, Shimizu Y. Advances in regenerative therapy: A review of the literature and future directions. Regenerative Therapy. 2020;14:136-153.
- 29. Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int. 2014;2014:965849.
- 30. Kichenbrand C, Velot E, Menu P, Moby V. Dental Pulp Stem Cell-Derived Conditioned Medium: An Attractive Alternative for Regenerative Therapy. Tissue engineering Part B, Reviews. 2019;25(1):78-88.
- 31. Vackovcá I, Kubinová S. Stem cell conditioned medium for cell-free therapies. Ceskoslovenska fysiologie. 2016;65(1):25-31.
- 32. Zhang Q, Huang Y, Sun J, Gu T, Shao X, Lai D. Immunomodulatory effect of human amniotic epithelial cells on restoration of ovarian function in mice with autoimmune ovarian disease. Acta biochimica et biophysica Sinica. 2019;51(8):845-855.
- 33. Mohamed SA, Shalaby S, Brakta S, Elam L, Elsharoud A, Al-Hendy A. Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency. Biomedicines. 2019;7(1):7.
- 34. Zhang Q, Bu S, Sun J, et al. Paracrine effects of human amniotic epithelial cells protect against chemotherapy-induced ovarian damage. Stem cell research & therapy. 2017;8(1):270.
- 35. Ding C, Zou Q, Wu Y, et al. EGF released from human placental mesenchymal stem cells improves premature ovarian insufficiency via NRF2/HO-1 activation. Aging (Albany NY). 2020;12(3):2992-3009.
- 36. Ivanova-Todorova E, Bochev I, Dimitrov R, et al. Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4+FOXP3+ cells and increases IL-10 secretion. J Biomed Biotechnol. 2012;2012:295167-295167.
- 37. Su J, Ding L, Cheng J, et al. Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency. Hum Reprod. 2016;31(5):1075-1086.
- 38. Huang B, Lu J, Ding C, Zou Q, Wang W, Li H. Exosomes derived from human adipose mesenchymal stem cells improve ovary function of premature ovarian insufficiency by targeting SMAD. Stem cell research & therapy. 2018;9(1):1-12.
- 39. Halıcıoğlu BŞ. Farkli deneysel prematür over yetmezlİğİ modellerİnde kök hücre tedavİsİnİn etkİnlİğİ [PhD thesis]. Manisa: Manisa Celal Bayar University; 2020.
Effects of adipose tissue derived mesenchymal stem cells and conditioned medium on experimental premature ovarian insufficiency model
Öz
Purpose: The aim of this study was to investigate the effects of adipose tissue derived mesenchymal stem cells (ADMSC) and conditioned medium (CM), which can be recommended for the treatment of chemotherapy-induced premature ovarian insufficiency (POI), on oxidative stress and apoptosis.
Materials and Methods: In the study, adult female Wistar albino rats were divided into 4 groups; Control, POI, POI+ADMSC, POI+CM. H&E staining was performed for histopathological evaluations in the ovary and all ovarian follicles were counted. iNOS and Caspase3 expressions were shown immunohistochemically as markers of oxidative stress and apoptosis.
Results: Follicular cell degenerations and vacuolization were observed in the ovaries of the POI group, while significant decreases were observed in these degenerations in the ADMSC and CM groups. Increased iNOS and Caspase3 expressions in the POI group were statistically significant decreased in both the ADMSC and CM groups.
Conclusion: Mesenchymal stem cells and cell-free conditioned medium, which are increasingly used in the field of regenerative medicine, can be an alternative treatment strategy for POI by reducing apoptosis and oxidative stress, which are the main mechanisms of the disease.
Anahtar Kelimeler
premature ovarian insufficiency adipose derived mesenchymal stem cell conditioned medium apoptosis oxidative stress
Proje Numarası
2019-021
Kaynakça
- 1. Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, van Wijnen AJ, Cool SM. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem cells translational medicine. 2017;6(12):2173-2185.
- 2. Esfandyari S, Chugh RM, Park H-s, Hobeika E, Ulin M, Al-Hendy A. Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility. Cells. 2020;9(10):2253.
- 3. Fazeli Z, Abedindo A, Omrani MD, Ghaderian SMH. Mesenchymal stem cells (MSCs) therapy for recovery of fertility: a systematic review. Stem Cell Reviews and Reports. 2018;14(1):1-12.
- 4. Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfusion Medicine and Hemotherapy. 2016;43(4):268-274.
- 5. Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15(6):641-648.
- 6. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends in biotechnology. 2006;24(4):150-154.
- 7. Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circulation research. 2007;100(9):1249-1260.
- 8. Zhu Y, Liu T, Song K, Fan X, Ma X, Cui Z. Adipose‐derived stem cell: a better stem cell than BMSC. Cell Biochemistry and Function: Cellular biochemistry and its modulation by active agents or disease. 2008;26(6):664-675.
- 9. Sun M, Wang S, Li Y, et al. Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure. Stem cell research & therapy. 2013;4(4):80.
- 10. Bogatcheva N, Coleman M. Conditioned Medium of Mesenchymal Stromal Cells: A New Class of Therapeutics. Biochemistry (Moscow). 2019;84(11):1375-1389.
- 11. Kim HO, Choi S-M, Kim H-S. Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders. Tissue Engineering and Regenerative Medicine. 2013;10(3):93-101.
- 12. Park B-S, Kim W-S, Choi J-S, et al. Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion. Biomedical Research. 2010;31(1):27-34.
- 13. Di Santo S, Yang Z, von Ballmoos MW, et al. Novel cell-free strategy for therapeutic angiogenesis: in vitro generated conditioned medium can replace progenitor cell transplantation. PLoS One. 2009;4(5):e5643.
- 14. Mirabella T, Cilli M, Carlone S, Cancedda R, Gentili C. Amniotic liquid derived stem cells as reservoir of secreted angiogenic factors capable of stimulating neo-arteriogenesis in an ischemic model. Biomaterials. 2011;32(15):3689-3699.
- 15. Mishra PJ, Mishra PJ, Banerjee D. Cell-free derivatives from mesenchymal stem cells are effective in wound therapy. World Journal of Stem Cells. 2012;4(5):35.
- 16. ESHRE. Management of women with premature ovarian insufficiency, 2015.
- 17. Santoro NF, Cooper AR. Primary Ovarian Insufficiency: a Clinical Guide to Early Menopause: Springer, 2016.
- 18. Shelling AN. Premature ovarian failure. Reproduction. 2010.
- 19. Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Human reproduction update. 2001;7(6):535-543.
- 20. Byrne J, Fears TR, Gail MH, et al. Early menopause in long-term survivors of cancer during adolescence. American Journal of Obstetrics & Gynecology. 1992;166(3):788-793.
- 21. Hao X, Anastácio A, Liu K, Rodriguez-Wallberg KA. Ovarian Follicle Depletion Induced by Chemotherapy and the Investigational Stages of Potential Fertility-Protective Treatments-A Review. International journal of molecular sciences. 2019;20(19):4720.
- 22. Jeelani R, Khan SN, Shaeib F, et al. Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality. Free Radical Biology and Medicine. 2017;110:11-18.
- 23. Szymanska KJ, Tan X, Oktay K. Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging. Molecular Human Reproduction. 2020;26(8):553-566.
- 24. Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertility and sterility. 2016;106(7):1588-1599.
- 25. Chen L, Guo S, Wei C, Li H, Wang H, Xu Y. Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report. Experimental and therapeutic medicine. 2018;15(5):4105-4118.
- 26. Kasap B, Kasap Ş, Vatansever S, et al. Effects of adipose and bone marrow-derived mesenchymal stem cells on vaginal atrophy in a rat menopause model. Gene. 2019;711:143937.
- 27. Brini AT, Amodeo G, Ferreira LM, et al. Therapeutic effect of human adipose-derived stem cells and their secretome in experimental diabetic pain. Scientific Reports. 2017;7(1):9904.
- 28. Ntege EH, Sunami H, Shimizu Y. Advances in regenerative therapy: A review of the literature and future directions. Regenerative Therapy. 2020;14:136-153.
- 29. Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int. 2014;2014:965849.
- 30. Kichenbrand C, Velot E, Menu P, Moby V. Dental Pulp Stem Cell-Derived Conditioned Medium: An Attractive Alternative for Regenerative Therapy. Tissue engineering Part B, Reviews. 2019;25(1):78-88.
- 31. Vackovcá I, Kubinová S. Stem cell conditioned medium for cell-free therapies. Ceskoslovenska fysiologie. 2016;65(1):25-31.
- 32. Zhang Q, Huang Y, Sun J, Gu T, Shao X, Lai D. Immunomodulatory effect of human amniotic epithelial cells on restoration of ovarian function in mice with autoimmune ovarian disease. Acta biochimica et biophysica Sinica. 2019;51(8):845-855.
- 33. Mohamed SA, Shalaby S, Brakta S, Elam L, Elsharoud A, Al-Hendy A. Umbilical Cord Blood Mesenchymal Stem Cells as an Infertility Treatment for Chemotherapy Induced Premature Ovarian Insufficiency. Biomedicines. 2019;7(1):7.
- 34. Zhang Q, Bu S, Sun J, et al. Paracrine effects of human amniotic epithelial cells protect against chemotherapy-induced ovarian damage. Stem cell research & therapy. 2017;8(1):270.
- 35. Ding C, Zou Q, Wu Y, et al. EGF released from human placental mesenchymal stem cells improves premature ovarian insufficiency via NRF2/HO-1 activation. Aging (Albany NY). 2020;12(3):2992-3009.
- 36. Ivanova-Todorova E, Bochev I, Dimitrov R, et al. Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4+FOXP3+ cells and increases IL-10 secretion. J Biomed Biotechnol. 2012;2012:295167-295167.
- 37. Su J, Ding L, Cheng J, et al. Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency. Hum Reprod. 2016;31(5):1075-1086.
- 38. Huang B, Lu J, Ding C, Zou Q, Wang W, Li H. Exosomes derived from human adipose mesenchymal stem cells improve ovary function of premature ovarian insufficiency by targeting SMAD. Stem cell research & therapy. 2018;9(1):1-12.
- 39. Halıcıoğlu BŞ. Farkli deneysel prematür over yetmezlİğİ modellerİnde kök hücre tedavİsİnİn etkİnlİğİ [PhD thesis]. Manisa: Manisa Celal Bayar University; 2020.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Klinik Tıp Bilimleri, Klinik Tıp Bilimleri (Diğer) |
| Bölüm | Araştırma |
| Yazarlar | |
| Proje Numarası | 2019-021 |
| Yayımlanma Tarihi | 30 Haziran 2021 |
| Kabul Tarihi | 26 Şubat 2021 |
| Yayımlandığı Sayı | Yıl 2021 Cilt: 46 Sayı: 2 |
