Kemik iliği kaynaklı mezenkimal kök hücrelerin deneysel Asherman modeli üzerine antiapoptotik ve proliferatif etkisi

Yıl 2019, Cilt: 44 Sayı: Ek 1, 434 - 446, 29.12.2019

Şamil Öztürk Pınar Kılıçaslan Sönmez İlhan Özdemir Yunus Emre Topdağı Mehmet İbrahim Tuğlu

https://doi.org/10.17826/cumj.573200

Cited By: 3

Öz

Amaç: Bu çalışmada Asherman sendromundaki (AS)endometriyal hasarlarda cerrahi yöntemlere ve medikal tedavilere alternatif olarak kök hücre tedavisinin etkileri araştırılmıştır.  

Gereç ve Yöntem: Bu çalışmada sıçanlarda AS modeli kimyasal olarak oluşturuldu. Aynı türün erkek bireylerinin tibia ve femur kemiğinden izole edilen kemik iliği kaynaklı mezenkimal kök hücreler (KİMKH) AS oluşturulan dişi sıçanlara verilerek endometriyumda meydana gelen değişiklikler histopatolojik parametrelerle değerlendirildi. Asherman+ besiyeri, Asherman+ niş, Asherman+ KİMKH, Asherman+ KİMKH+ niş olmak üzere toplam dört grup oluşturuldu.

Bulgular: Tedavi gruplarında epitel ve lamina propriyadaki rejenerasyonla birilkte endometriyal kalınlığın, bez sayısının ve vaskülarizasyonun arttığı, fibröz alanların ve apoptotik hücre ölümünün azaldığı  gözlenmiştir. Kontrol grubu olarak değerlendirilen sağ uterin hornlarda ise her hangi bir histopatolojik değişiklik görülmemiştir.

Sonuç: KİMKH ve Niş uygulamalarının, infertiliteye neden olan mekanizmaların içerisinde yer alan adezyon oluşumunu azaltarakedavi ile kliniğe katkı sağlayabileceği gösterildi. Bu olumlu sonuçlar Asherman çalışmalarının kliniğe taşınabilmesi açısından ümit vericidir.

Anahtar Kelimeler

Mezenkimal kök hücre, Asherman sendromu, Apoptozis, İnfertilite, , Histoloji

Destekleyen Kurum

Kurum veya şahıs desteği alınmamıştır.

Antiapoptotic and proliferative effect of bone marrow-derived mesenchymal stem cells on experimental Asherman model

Öz

Purpose: We investigated the effects of stem cell therapy as an alternative to surgical methods and medical treatments in endometrial injuries in Asherman syndrome (AS).

Materials and Methods: In this study, AS model was created chemically in rats. The bone marrow-derived mesenchymal stem cells isolated from the tibia and femoral bone of male individuals of the same species (BMDSC) were given to female rats with asherman syndrome and the changes in the endometrium were evaluated by histopathological parameters. Asherman + medium, Asherman + niche, Asherman + BMDSCs, Asherman + BMDSCs + niche were formed in four groups.

Results: It was observed that increased endometrial thickness, gland count and vascularization and decreased fibrous areas and apoptotic cell death with regeneration in epithelium and lamina propria in treatment groups. No histopathologic changes were observed in the right uterine horns, which were evaluated as control group. . 

Conclusion: BMDSCs and Niche applications can contribute to the clinic by reducing the formation of adhesion within the mechanisms causing infertility. These positive results are promising in terms of transporting Asherman studies to the clinic.It has been shown that BMDSCs and Niche may contribute to the clinic by treatment with adhesion molecules in mechanisms that cause infertility.

Anahtar Kelimeler

Mesenchymal stem cell, Asherman syndrome, Apoptosis, Infertility, Histology

Kaynakça

• 1. March CM. Management of Asherman’s syndrome. Reproductive BioMedicine Online. 2010; 23:63– 76.
• 2. Deans R, Abbott J. Review of intrauterine adhesions. J.Minim inv.surg. 2010;17(5): 555-569.
• 3. Yuksel B, Kılıc S, Boztok B, Albayrak A. An Experimental Asherman Syndrome, Rat Model. Turkiye Klinikleri J Gynecol Obst. 2014;24(4):195-7.
• 4. Yu D, Wong YM, Cheong Y, et al. Asherman syndrome-one century later. Fertil Steril. 2008;89:759-79.
• 5. Roman H, Sentilhes L, Cingotti M, et al. Uterine devascularization and subsequent major intrauterine synechiae and ovarian failure. Fertil Steril. 2005;83:755–7.6. Weissman IL. Stem cells:units of development, units of regeneration, and units in evolution. Cell. 2000;100:157-168.
• 7. Zhang J, Li L. Stem cell niche: microenvironment and beyond. J Biol Chem. 2008; 283(15):9499-503. doi: 10.1074/jbc.R700043200.
• 8. Conway A, Schaffer DV. Biophysical regulation of stem cell behavior within the niche. Stem Cell Res Ther. 2012; 3(6):50. doi: 10.1186/scrt141.
• 9. Krause DS, Scadden DT, Preffer FI. The hematopoietic stem cell niche--home for friend and foe? Cytometry B Clin Cytom. 2013;84(1):7-20. doi:10.1002/cyto.b.21066.
• 10. Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J. Cell. Physiol. 1999;181(1): 67-73.11. Alhadlaq A, Mao JJ. Mesenchymal stem cells: isolation and therapeutics. Stem. Cells and Dev. 2004;13(4):436-448.
• 12. Kilic S, Yuksel B, Pinarli F, et al. Effect of stem cell application on Asherman syndrome, an experimental rat model. J Assist Reprod Genet. 2014; 31(8): 975–982. doi: 10.1007/s10815-014-0268-2.
• 13. Niemeyer P, Fechner K, Milz S, et al. Comparison of mesenchymal stem cells from bone marrow and adiposetissue for bone regeneration in a critical size defect of the sheep tibia and theinfluence of platelet-rich plasma. Biomaterials 2010; 31(13):3572-9.
• 14. Karaoz E, Aksoy A, Ayhan S, et al. Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol. 2009;132:533-46.
• 15. Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman’s syndrome). Fertil Steril. 2008;90(2):409–14.16. Abbott J, Thomson A, Vancaillie T. SprayGel following surgery for Asherman’s syndrome may improve pregnancy outcome. J Obstet Gynaecol. 2004;24(6):710–1.
• 17. Amer MI, Abd-El-Maeboud KH. Amnion graft following hysteroscopic lysis of intrauterine adhesions. J Obstet Gynaecol Res. 2006;32: 559–66.
• 18. Tsapanos VS, StathopoulouLP, Papathanassopoulou VS, Tzingounis VA. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. J Biomed Mater Res. 2002;63: 10–4.
• 19. Orhue AA, Aziken ME, Igbefoh JO. A comparison of two adjunctive treatments for intrauterine adhesions following lysis. Int J Gynaecol Obstet. 2003;82:49–56.
• 20. Lin X, Wei M, Li TC, Huang Q, et al. A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study. Eur J Obstet Gynecol Reprod Biol. 2013;S0301-2115(13): 00325–4.
• 21. Nagori CB, Panchal SY, Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman’s syndrome. J Hum Reprod Sci. 2011;4:43–8.
• 22. Cervello´ I, Gil-Sanchis C, Mas A, et al. Bone marrowderived cells from male donors do not contribute to the endometrial side population of the recipient. PLoS One. 2012;7(1):e30260. doi: 10.1371/journal.pone.0030260.
• 23. Curley GF, Hayes M, Ansari B, et al. Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax. 2012;67:496–501.
• 24. Wang N, Li Q, Zhang L, et al. Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6. PLoS One. 2012;7:e43768.25. Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: the first 10 years. Hum Reprod. 2016;22:137–63.
• 26. Tan J, Li P, Wang Q, Li Y, et al. Autologous menstrual blood-derived stromal cells transplantation for severe Asherman’s syndrome. Hum Reprod. 2016;31:2723–9.
• 27. Jing Z, Qiong Z, Yonggang W, Yanping L. Rat bone marrow mesenchymal stem cells improve regeneration of thin endometriyum in rat. Fertil Steril. 2014; 101(2):587-94.
• 28. Kuramoto G, Takagi S, Ishitani K, et al. Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions. Hum Reprod. 2015;30:406–16.
• 29. Song T, Zhao X, Sun H, et al. Regeneration of uterine horns in rats using collagen scaffolds loaded with human embryonic stem cell-derived endometrium-like cells. Tissue Eng Part A. 2015;21:353–61.
• 30. Asherman sendromu şematik görünüm. http://planbwellness.com/adhesion. (Erişim; 20.05.2019).