Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections

TİRYAKİ, MERAL; Kabalcı, Mehmet; Cirpar, Meric; Canbeyli, Ibrahim Deniz; Oktas, Birhan

doi:10.5606/ehc.2019.66162

Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections

İbrahim Deniz CANBEYLİ, (Kırıkkale Üniversitesi, Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kırıkkale, Türkiye)

Mehmet KABALCI, (Kırıkkale Üniversitesi, Tıp Fakültesi, Kalp Damar Cerrahisi Anabilim Dalı, Kırıkkale, Türkiye)

Meriç ÇIRPAR, (Kırıkkale Üniversitesi, Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kırıkkale, Türkiye)

Meral TİRYAKİ, (Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Patoloji Anabilim Dalı, Ankara, Türkiye)

Birhan OKTAŞ (Kırıkkale Üniversitesi, Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kırıkkale, Türkiye)

Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.)

1 0

Yıl: 2019 Cilt: 30 Sayı: 3 Sayfa Aralığı: 201 - 211 Metin Dili: İngilizce DOI: 10.5606/ehc.2019.66162 İndeks Tarihi: 20-11-2020

Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections

Öz:

Objectives: This study aims to evaluate the effects of mesenchymal stemcell (MSC) implantation on vascular graft infections caused by methicillinresistantStaphylococcus epidermidis (MRSE) and compare with antibiotictreatment.Materials and methods: Healthy adult 56 Wistar rats (age, over5 months; weighing, 300-350 g) were divided into eight groups. Group 1was defined as the control group and group 2 was defined as the infectedcontrol group. Groups 3 and 4 were defined as Dacron grafted and MRSEinfected groups, treated with tigecycline and MSCs, respectively. Groups 5and 6 were performed polytetrafluoroethylene (PTFE) graft and infectedwith MRSE. These groups were also administered tigecycline and MSCtreatment, respectively. Groups 7 and 8 were infected with MRSE withoutgraft administration and were also performed tigecycline and MSCtreatment, respectively. Grafts and soft tissue specimens were collected at13 days postoperatively. Colony counts of peri-graft tissue were performed.All samples were evaluated by enzyme-linked immunosorbent assay(ELISA) for the markers that determine stem cell activity.Results: The overall success of the treatments was assessed by thenumber of rats with MRSE recurrence, regardless of graft used. Thedifference between the untreated group 2, tigecycline groups (3, 5 and 7)and MSCs groups (4, 6 and 8) were statistically significant. Success of MSCand tigecycline treatments was similar in Dacron, PTFE, and non-graftedgroups. There was a resistance of MRSE infection in Dacron groups toMSC and tigecycline treatments. This was considered to be indicative ofthe susceptibility of the Dacron grafts to infection. However, there wasno significant difference between group 2 and Dacron groups in terms ofbacterial colonization. ELISA results were significant in three cytokines.Conclusion: Mesenchymal stem cells can be considered as an alternativetreatment option on its own or part of a combination therapy for control ofvascular graft infections.

Anahtar Kelime:

Mezenkimal kök hücreler metisiline dirençli Stafilokokus epidermidis vasküler greft enfeksiyonları üzerinde önemli anti-enfektif etkiye sahiptir

Öz:

Amaç: Bu çalışmada, mezenkimal kök hücre (MKH) implantasyonunun metisiline dirençli Stafilokokus epidermidis (MDSE)’in neden olduğu vasküler greft enfeksiyonları üzerindeki etkileri değerlendirildi ve antibiyotik tedavisi ile karşılaştırıldı. Gereç ve yöntemler: Sağlıklı erişkin 56 Wistar sıçanı (yaş, 5 ay üzeri; ağırlık, 300-350 g) sekiz gruba ayrıldı. Grup 1 kontrol grubu, grup 2 enfekte kontrol grubu olarak tanımlandı. Grup 3 ve 4 Dakron grefti uygulanan, MDSE ile enfekte olan, sırasıyla tigesiklin ve MKH tedavisi uygulanan gruplar olarak tanımlandı. Grup 5 ve 6 politetrafloroetilen (PTFE) greft uygulanarak MDSE ile enfekte edildi. Bu gruplara da sırasıyla tigesiklin ve MKH tedavisi uygulandı. Grup 7 ve 8 greft uygulanmadan, MDSE ile enfekte edildi ve sırasıyla bu gruplara da tigesiklin ve MKH tedavisi uygulandı. Greftler ve yumuşak doku örnekleri ameliyattan 13 gün sonra alındı. Greft çevresi dokuda koloni sayımı yapıldı. Tüm numuneler, kök hücre aktivitesini gösteren belirteçler açısından enzime bağlı bağışıklık deneyi (ELISA) ile değerlendirildi. Bulgular: Tedavilerin genel başarısı, kullanılan greftten bağımsız olarak, MDSE rekürrensi olan sıçanların sayısı ile değerlendirildi. Tedavi edilmeyen grup 2, tigesiklin grupları (3, 5 ve 7) ile MKH grupları (4, 6 ve 8) arasındaki farklılık istatistiksel olarak anlamlıydı. Mezenkimal kök hücre ve tigesiklin tedavilerinin başarısı Dakron, PTFE ve greft uygulanmayan gruplarda benzerdi. Dakron gruplarında MDSE enfeksiyonunun hem MKH hem de tigesiklin tedavisine karşı bir direnci vardı. Bu, Dakron greftlerinin enfeksiyona duyarlılığının bir göstergesi olarak kabul edildi. Ancak, grup 2 ve Dakron grupları arasında bakteriyel kolonizasyon açısından anlamlı farklılık yoktu. ELISA sonuçları üç sitokinde anlamlıydı. Sonuç: Mezenkimal kök hücreler, tek başına alternatif bir tedavi seçeneği veya vasküler greft enfeksiyonlarının kontrolü için kombine terapinin bir parçası olarak kabul edilebilir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Caudle RJ, Stern PJ. Severe open fractures of the tibia. J Bone Joint Surg [Am] 1987;69:801-7.
2. Howe HR Jr, Poole GV Jr, Hansen KJ, Clark T, Plonk GW, Koman LA, et al. alvage of lower extremities following combined orthopedic and vascular trauma. A predictive salvage index. Am Surg 1987;53:205-8.
3. Frisvoll C, Clarke-Jenssen J, Madsen JE, Flugsrud G, Frihagen F, Andreassen GS, et al. Long-term outcomes after high-energy open tibial fractures: Is a salvaged limb superior to prosthesis in terms of physical function and quality of life? Eur J Orthop Surg Traumatol 2019;29:899-906.
4. Legout L, D'Elia PV, Sarraz-Bournet B, Haulon S, Meybeck A, Senneville E, et al. Diagnosis and management of prosthetic vascular graft infections. Med Mal Infect. 2012;42:102-9.
5. Erb S1, Sidler JA1, Elzi L1, Gurke L2, Battegay M1, Widmer AF, et al. Surgical and antimicrobial treatment of prosthetic vascular graft infections at different surgical sites: a retrospective study of treatment outcomes. PLoS One 2014;9:e112947.
6. Halvorson JJ, Anz A, Langfitt M, Deonanan JK, Scott A, Teasdall RD, et al. Vascular injury associated with extremity trauma: initial diagnosis and management. J Am Acad Orthop Surg 2011;19:495-504.
7. Herscu G, Wilson SE. Prosthetic infection: lessons from treatment of the infected vascular graft. Surg Clin North Am 2009;89:391-401
8. Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med 2004;350:1422-9
9. Bergamini TM, Corpus RA Jr, Brittian KR, Peyton JC, Cheadle WG. The natural history of bacterial biofilm graft infection. J Surg Res 1994;56:393-6.
10. Sacar S, Sacar M, Kaleli I, Toprak S, Cevahir N, Teke Z, et al. Linezolid compared with vancomycin for the prevention of methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis vascular graft infection in rats: A randomized, controlled, experimental study. Curr Ther Res Clin Exp 2007;68:23-31.
11. Elens M, Dusoruth M, Astarci P, Mastrobuoni S, Bosiers MJ, Nardella J, et al. Management and Outcome of Prosthetic Vascular Graft Infections: A Single Center Experience. Vasc Endovascular Surg 2018;52:181-87.
12. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006;107:367-72.
13. Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther 2016;7:125.
14. Matthay MA, Pati S, Lee JW. Concise review: Mesenchymal stem (Stromal) cells: Biology and preclinical evidence for therapeutic potential for organ dysfunction following trauma or sepsis. Stem Cells 2017;35:316-324.
15. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 2009;5:54-63.
16. Kota DJ, Wiggins LL, Yoon N, Lee RH. TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity. Diabetes 2013;62:2048-58.
17. Baron F, Storb R. Mesenchymal stromal cells: a new tool against graft-versus-host disease? Biol Blood Marrow Transplant 2012;18:822-40.
18. Devaney J, Horie S, Masterson C, Elliman S, Barry F, O’Brien T, et al. Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax 2015;70:625-35.
19. Horák J, Nalos L, Martínková V, Beneš J, Štengl M, Matějovič M. Mesenchymal stem cells in sepsis and associated organ dysfunction: A promising future or blind alley? Stem Cells Int 2017;2017:7304121.
20. Asano K, Yoshimura S, Nakane A. Adipose tissuederived mesenchymal stem cells attenuate staphylococcal enterotoxin a-induced toxic shock. Infect Immun 2015;83:3490-6.
21. Pedrazza L, Lunardelli A, Luft C, Cruz CU, de Mesquita FC, Bitencourt S, et al. Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model. Inflamm Res 2014;63:719-28.
22. Eren Y, Adanır O, Dinçel YM, Genç E, Arslan YZ, Çağlar A. Effects of low molecular weight heparin and rivaroxaban on rat Achilles tendon healing. Eklem Hastalik Cerrahisi 2018;29:13-9.
23. Seguin JC, Walker RD, Caron JP, Kloos WE, George CG, Hollis RJ, et al. Methicillin-resistant Staphylococcus aureus outbreak in a veterinary teaching hospital: potential human-to-animal transmission. J Clin Microbiol 1999;37:1459-63.
24. Goessens WH, Mouton JW, Ten Kate MT, Sörgel F, Kinzig M, Bakker-Woudenberg IA. The therapeutic effect of tigecycline, unlike that of Ceftazidime, is not influenced by whether the Klebsiella pneumoniae strain produces extendedspectrum beta-lactamases in experimental pneumonia in rats. Antimicrob Agents Chemother 2013;57:643-6.
25. Schneider S, Unger M, van Griensven M, Balmayor ER. Adipose-derived mesenchymal stem cells from liposuction and resected fat are feasible sources for regenerative medicine. Eur J Med Res 2017;22:17.
26. Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018;93:19-31.
27. Mori Y, Ohshimo J, Shimazu T, He H, Takahashi A, Yamamoto Y, et al. Improved explant method to isolate umbilical cord-derived mesenchymal stem cells and their immunosuppressive properties. Tissue Eng Part C Methods 2015;21:367-72.
28. Talaei-Khozani T, Borhani-Haghighi M, Ayatollahi M, Vojdani Z. An in vitro model for hepatocyte-like cell differentiation from Wharton’s jelly derived-mesenchymal stem cells by cell-base aggregates. Gastroenterol Hepatol Bed Bench 2015;8:188-99.
29. Hernández-Richter T, Schardey HM, Wittmann F, Mayr S, Schmitt-Sody M, Blasenbreu S, et al. Rifampin and Triclosan but not silver is effective in preventing bacterial infection of vascular dacron graft material. Eur J Vasc Endovasc Surg 2003;26:550-7.
30. Takahashi H, Sakata N, Yoshimatsu G, Hasegawa S, Kodama S. Regenerative and Transplantation Medicine: Cellular Therapy Using Adipose Tissue-Derived Mesenchymal Stromal Cells for Type 1 Diabetes Mellitus. J Clin Med 2019;8. pii: E249.
31. Sarıkaya B, Yumuşak N, Yigin A, Sipahioğlu S, Yavuz Ü, Altay MA. Comparison of the effects of human recombinant epidermal growth factor and platelet-rich plasma on healing of rabbit patellar tendon. Eklem Hastalik Cerrahisi 2017;28:92-9.
32. Chiswick EL, Duffy E, Japp B, Remick D. Detection and quantification of cytokines and other biomarkers. Methods Mol Biol 2012;844:15-30.
33. O’Connor S, Andrew P, Batt M, Becquemin JP. A systematic review and meta-analysis of treatments for aortic graft infection. J Vasc Surg 2006;44:38-45.
34. Legout L, Sarraz-Bournet B, D’Elia PV, Devos P, Pasquet A, Caillaux M, et al. Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective observational cohort study. Clin Microbiol Infect 2012;18:352-8.
35. Lee JYH, Monk IR, Gonçalves da Silva A, Seemann T, Chua KYL, Kearns A, et al. Global spread of three multidrugresistant lineages of Staphylococcus epidermidis. Nat Microbiol 2018;3:1175-85.
36. Bhattacharya M, Parakh A, Narang M. Tigecycline. J Postgrad Med 2009;55:65-8.
37. Cai Y, Li R, Liang B, Bai N, Liu Y, Wang R. In vitro antimicrobial activity and mutant prevention concentration of colistin against Acinetobacter baumannii. Antimicrob Agents Chemother 2010;54:3998-9.
38. Shen F, Han Q, Xie D, Fang M, Zeng H, Deng Y. Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs. Int J Infect Dis 2015;39:25-33.
39. Moresco EM, LaVine D, Beutler B. Toll-like receptors. Curr Biol 2011;21:R488-93.
40. Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009;15:42-9.
41. Furie MB, Randolph GJ. Chemokines and tissue injury. Am J Pathol 1995;146:1287-301.
42. Kaneider NC, Leger AJ, Kuliopulos A. Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions. FEBS J 2006;273:4416-24.
43. Bartosh TJ, Ylöstalo JH, Bazhanov N, Kuhlman J, Prockop DJ. Dynamic compaction of human mesenchymal stem/ precursor cells into spheres self-activates caspasedependent IL1 signaling to enhance secretion of modulators of inflammation and immunity (PGE2, TSG6, and STC1). Stem Cells 2013;31:2443-56.
44. Schmitt DD, Bandyk DF, Pequet AJ, Towne JB. Bacterial adherence to vascular prostheses. A determinant of graft infectivity. J Vasc Surg 1986;3:732-40.

APA	Canbeyli I, Kabalcı M, Cirpar M, TİRYAKİ M, Oktas B (2019). Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. , 201 - 211. 10.5606/ehc.2019.66162
Chicago	Canbeyli Ibrahim Deniz,Kabalcı Mehmet,Cirpar Meric,TİRYAKİ MERAL,Oktas Birhan Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. (2019): 201 - 211. 10.5606/ehc.2019.66162
MLA	Canbeyli Ibrahim Deniz,Kabalcı Mehmet,Cirpar Meric,TİRYAKİ MERAL,Oktas Birhan Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. , 2019, ss.201 - 211. 10.5606/ehc.2019.66162
AMA	Canbeyli I,Kabalcı M,Cirpar M,TİRYAKİ M,Oktas B Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. . 2019; 201 - 211. 10.5606/ehc.2019.66162
Vancouver	Canbeyli I,Kabalcı M,Cirpar M,TİRYAKİ M,Oktas B Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. . 2019; 201 - 211. 10.5606/ehc.2019.66162
IEEE	Canbeyli I,Kabalcı M,Cirpar M,TİRYAKİ M,Oktas B "Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections." , ss.201 - 211, 2019. 10.5606/ehc.2019.66162
ISNAD	Canbeyli, Ibrahim Deniz vd. "Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections". (2019), 201-211. https://doi.org/10.5606/ehc.2019.66162

APA	Canbeyli I, Kabalcı M, Cirpar M, TİRYAKİ M, Oktas B (2019). Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.), 30(3), 201 - 211. 10.5606/ehc.2019.66162
Chicago	Canbeyli Ibrahim Deniz,Kabalcı Mehmet,Cirpar Meric,TİRYAKİ MERAL,Oktas Birhan Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.) 30, no.3 (2019): 201 - 211. 10.5606/ehc.2019.66162
MLA	Canbeyli Ibrahim Deniz,Kabalcı Mehmet,Cirpar Meric,TİRYAKİ MERAL,Oktas Birhan Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.), vol.30, no.3, 2019, ss.201 - 211. 10.5606/ehc.2019.66162
AMA	Canbeyli I,Kabalcı M,Cirpar M,TİRYAKİ M,Oktas B Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.). 2019; 30(3): 201 - 211. 10.5606/ehc.2019.66162
Vancouver	Canbeyli I,Kabalcı M,Cirpar M,TİRYAKİ M,Oktas B Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections. Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.). 2019; 30(3): 201 - 211. 10.5606/ehc.2019.66162
IEEE	Canbeyli I,Kabalcı M,Cirpar M,TİRYAKİ M,Oktas B "Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections." Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.), 30, ss.201 - 211, 2019. 10.5606/ehc.2019.66162
ISNAD	Canbeyli, Ibrahim Deniz vd. "Mesenchymal stem cells have significant anti-infective effect on methicillin-resistant Staphylococcus epidermidis vascular graft infections". Eklem Hastalıkları ve Cerrahisi Dergisi (Eski Adı: Artroplasti Artroskopik Cerrahi Derg.) 30/3 (2019), 201-211. https://doi.org/10.5606/ehc.2019.66162