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Dental Folikül Mezenkimal Kök Hücreleri Amyotrofik Lateral Skleroz Hastalarının Lenfositlerinde CD4+Foxp3+ T-Regülatör Hücreleri Arttırdı

Year 2017, Volume: 7 Issue: 3, 85 - 90, 15.09.2017

Abstract

Amaç: Amyotrofik lateral skleroz (ALS) motor nöronların dejenerasyonuna sebep olan bir hastalıktır. Günümüzde ALS tedavisinde kullanılan tek ilaç riluzoldür; ancak bu ilacın faydası sınırlıdır. Kök hücre temelli tedaviler ALS için yeni bir tedavi seçeneğidir ve bu hastalık üzerin anti-inflamatuar etkisi olduğu gösterilmiştir. Bu çalışmada dental folikül mezenkimal kök hücrelerin (DFSCs) ALS hastalarından izole edilen periferal kan mononükleer hücreler (PBMC) üzerindeki immün baskılayıcı etkisi araştırılmıştır.

 

Yöntemler: Sağlıklı bireylerin molar dişlerinden izole edilen DFSCs’ler PBMC izolasyonundan 48 saat önce 48 kuyulu hücre kültür plaklarına ekildi. ALS hastalarının ve sağlıklı bireylerin venöz kan örneklerinden PBMC izolasyonu yapıldı ve DFSCs’nin varlığında ve yokluğunda kültürü yapıldı. 72 saatlik kültür süresinin sonunda lenfosit proliferasyonu, apoptoz ve CD4+FoxP3+ regulator T hücre oranları analiz edildi.

 

Bulgular: DFSCs ile birlikte kültürü yapılan ALS hastalarının lenfositlerinde CD4+FoxP3+ regulator T hücre oranlarının arttığı ve lenfosit proliferasyonunda azalma olduğu gösterilmiştir. Bunun yanı sıra DFSCs’ler ALS hastalarının lenfositlerinde apoptotik etkiyi arttırırken sağlıklı bireylerin lenfositlerinde hücre canlılığını koruduğu gözlemlenmiştir.

 

Sonuç: Çalışmamızda DFSCs’in ALS hastalarının lenfositlerinde inflamatuar yanıt üzerinde baskılayıcı etkisi olduğu gösterilmiştir ve ALS dahil diğer nöroinflamatuar hastalıkların tedavisinde yeni bir seçenek olarak kullanılabilir.

References

  • 1. Mao Z, Zhang S, Chen H. Stem cell therapy for amyotrophic lateral sclerosis. Cell Regen (Lond) 2015; 4: 11. [CrossRef] 2. Chio A, Mora G, Calvo A, Mazzini L, Bottacchi E, Mutani R. Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology 2009; 72: 725-31. [CrossRef] 3. Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 2013; 14: 248-64. [CrossRef] 4. Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 2015; 347: 1436-41. [CrossRef] 5. Boillee S, Vande Velde C, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 2006; 52: 39-59. [CrossRef] 6. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet 2011; 377: 942-55. [CrossRef] 7. Giunti D, Parodi B, Usai C, Vergani L, Casazza S, Bruzzone S, et al. Mesenchymal stem cells shape microglia effector functions through the release of CX3CL1. Stem Cells 2012; 30: 2044-53. [CrossRef] 8. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood 2005; 106: 1755-61. [CrossRef] 9. Zhang J, Li Y, Lu M, Cui Y, Chen J, Noffsinger L, et al. Bone marrow stromal cells reduce axonal loss in experimental autoimmune encephalomyelitis mice. J Neurosci Res 2006; 84: 587-95. [CrossRef] 10. Lanza C, Morando S, Voci A, Canesi L, Principato MC, Serpero LD, et al. Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo. J Neurochem 2009; 110: 1674-84. [CrossRef] 11. Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 2006; 198: 54-64. [CrossRef] 12. Mao Z, Zhang S, Chen H. Stem cell therapy for amyotrophic lateral sclerosis. Cell Regeneration 2015; 4: 11. [CrossRef] 13. Vollner F, Ernst W, Driemel O, Morsczeck C. A two-step strategy for neuronal differentiation in vitro of human dental follicle cells. Differentiation 2009; 77: 433-41. [CrossRef] 14. Yildirim S, Zibandeh N, Genc D, Ozcan EM, Goker K, Akkoc T. The Comparison of the Immunologic Properties of Stem Cells Isolated from Human Exfoliated Deciduous Teeth, Dental Pulp, and Dental Follicles. Stem Cells International, July, 2015. 15. Lewis CA, Manning J, Rossi F, Krieger C. The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells. Neurol Res Int 2012; 2012: 803701. [CrossRef] 16. Troost D, Van den Oord JJ, Vianney de Jong JM. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 1990; 16: 401-10. [CrossRef] 17. Engelhardt JI, Tajti J, Appel SH. Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch Neurol 1993; 50: 30-6. [CrossRef] 18. Holmøy T. T cells in amyotrophic lateral sclerosis. Eur J Neurol 2008; 15: 360-6. [CrossRef] 19. Engelhardt B, Ransohoff RM. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 2005; 26: 485-95. [CrossRef] 20. McMahon EJ, Bailey SL, Miller SD. CNS dendritic cells: critical participants in CNS inflammation? Neurochem Int 2006; 49: 195-203. [CrossRef] 21. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-7. [CrossRef] 22. Weydt P, Yuen EC, Ransom BR, Möller T. Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 2004; 48: 179-82. [CrossRef] 23. Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, et al. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 2011; 134: 1293-314. [CrossRef] 24. Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders-time for clinical translation? J Clin Invest 2010; 120: 29-40. [CrossRef] 25. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 2013; 13: 392-402. [CrossRef] 26. Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, et al. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med 2013; 5: 64-79. [CrossRef] 27. Menon P, McKay F, Schibeci S, Booth D, Marmash N, Parnell G, et al. Regulatory T cells in amyotrophic lateral sclerosis: A role for disease modulation? J Clin Neurosci 2014; 21: 2050. [CrossRef]

Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients

Year 2017, Volume: 7 Issue: 3, 85 - 90, 15.09.2017

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) is a disorder that causes the degeneration of motor neurons. Currently, riluzole is the only effective drug used to treat ALS; however, it has limited clinical benefits. Stem cell-based therapy has been studied as a potential novel treatment strategy for ALS and has shown to have an anti-inflammatory effects when treating this disease. In this study, we studied the immunosuppressive effect of dental follicle mesenchymal stem cells (DFSCs) on peripheral blood mononuclear cells (PBMCs) of ALS patients.

 

Methods: DFSCs were isolated from the third molar teeth of healthy individuals, and cells were seeded in the 48 well plate 48 hours prior to PBMC isolation. PBMCs were isolated from venous blood samples of ALS patients and healthy volunteers and were cultured in the presence or absence of DFSCs. After 72 h of culture period lymphocyte proliferation, apoptosis and CD4+FoxP3+ regulatory T-cell ratios were analyzed.

 

Results: Analysis revealed an increase in the number of CD4+FoxP3+ regulatory T cells and a decrease in the proliferative responses of lymphocytes with DFSCs. In addition, DFSCs enhanced the apoptotic effect of the lymphocytes of ALS patients, but increased cell survival in healthy individuals.

 

Conclusion: Our study showed that DFSCs regulate inflammatory responses of lymphocytes in ALS patients and that they can be a novel therapeutic approach for treating neuroinflammatory diseases including ALS.

References

  • 1. Mao Z, Zhang S, Chen H. Stem cell therapy for amyotrophic lateral sclerosis. Cell Regen (Lond) 2015; 4: 11. [CrossRef] 2. Chio A, Mora G, Calvo A, Mazzini L, Bottacchi E, Mutani R. Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology 2009; 72: 725-31. [CrossRef] 3. Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 2013; 14: 248-64. [CrossRef] 4. Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 2015; 347: 1436-41. [CrossRef] 5. Boillee S, Vande Velde C, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 2006; 52: 39-59. [CrossRef] 6. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet 2011; 377: 942-55. [CrossRef] 7. Giunti D, Parodi B, Usai C, Vergani L, Casazza S, Bruzzone S, et al. Mesenchymal stem cells shape microglia effector functions through the release of CX3CL1. Stem Cells 2012; 30: 2044-53. [CrossRef] 8. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood 2005; 106: 1755-61. [CrossRef] 9. Zhang J, Li Y, Lu M, Cui Y, Chen J, Noffsinger L, et al. Bone marrow stromal cells reduce axonal loss in experimental autoimmune encephalomyelitis mice. J Neurosci Res 2006; 84: 587-95. [CrossRef] 10. Lanza C, Morando S, Voci A, Canesi L, Principato MC, Serpero LD, et al. Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo. J Neurochem 2009; 110: 1674-84. [CrossRef] 11. Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 2006; 198: 54-64. [CrossRef] 12. Mao Z, Zhang S, Chen H. Stem cell therapy for amyotrophic lateral sclerosis. Cell Regeneration 2015; 4: 11. [CrossRef] 13. Vollner F, Ernst W, Driemel O, Morsczeck C. A two-step strategy for neuronal differentiation in vitro of human dental follicle cells. Differentiation 2009; 77: 433-41. [CrossRef] 14. Yildirim S, Zibandeh N, Genc D, Ozcan EM, Goker K, Akkoc T. The Comparison of the Immunologic Properties of Stem Cells Isolated from Human Exfoliated Deciduous Teeth, Dental Pulp, and Dental Follicles. Stem Cells International, July, 2015. 15. Lewis CA, Manning J, Rossi F, Krieger C. The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells. Neurol Res Int 2012; 2012: 803701. [CrossRef] 16. Troost D, Van den Oord JJ, Vianney de Jong JM. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 1990; 16: 401-10. [CrossRef] 17. Engelhardt JI, Tajti J, Appel SH. Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch Neurol 1993; 50: 30-6. [CrossRef] 18. Holmøy T. T cells in amyotrophic lateral sclerosis. Eur J Neurol 2008; 15: 360-6. [CrossRef] 19. Engelhardt B, Ransohoff RM. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 2005; 26: 485-95. [CrossRef] 20. McMahon EJ, Bailey SL, Miller SD. CNS dendritic cells: critical participants in CNS inflammation? Neurochem Int 2006; 49: 195-203. [CrossRef] 21. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-7. [CrossRef] 22. Weydt P, Yuen EC, Ransom BR, Möller T. Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 2004; 48: 179-82. [CrossRef] 23. Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, et al. Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 2011; 134: 1293-314. [CrossRef] 24. Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders-time for clinical translation? J Clin Invest 2010; 120: 29-40. [CrossRef] 25. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell 2013; 13: 392-402. [CrossRef] 26. Henkel JS, Beers DR, Wen S, Rivera AL, Toennis KM, Appel JE, et al. Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol Med 2013; 5: 64-79. [CrossRef] 27. Menon P, McKay F, Schibeci S, Booth D, Marmash N, Parnell G, et al. Regulatory T cells in amyotrophic lateral sclerosis: A role for disease modulation? J Clin Neurosci 2014; 21: 2050. [CrossRef]
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Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Deniz Genç This is me

Noushin Zibandeh This is me

Kayıhan Uluç This is me

Pınar Kahraman Koytak This is me

Muazzez Gökalp This is me

Tülin Tanrıdağ This is me

Tunç Akkoç

Publication Date September 15, 2017
Submission Date February 6, 2017
Published in Issue Year 2017 Volume: 7 Issue: 3

Cite

APA Genç, D., Zibandeh, N., Uluç, K., Koytak, P. K., et al. (2017). Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients. Clinical and Experimental Health Sciences, 7(3), 85-90.
AMA Genç D, Zibandeh N, Uluç K, Koytak PK, Gökalp M, Tanrıdağ T, Akkoç T. Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients. Clinical and Experimental Health Sciences. September 2017;7(3):85-90.
Chicago Genç, Deniz, Noushin Zibandeh, Kayıhan Uluç, Pınar Kahraman Koytak, Muazzez Gökalp, Tülin Tanrıdağ, and Tunç Akkoç. “Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients”. Clinical and Experimental Health Sciences 7, no. 3 (September 2017): 85-90.
EndNote Genç D, Zibandeh N, Uluç K, Koytak PK, Gökalp M, Tanrıdağ T, Akkoç T (September 1, 2017) Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients. Clinical and Experimental Health Sciences 7 3 85–90.
IEEE D. Genç, N. Zibandeh, K. Uluç, P. K. Koytak, M. Gökalp, T. Tanrıdağ, and T. Akkoç, “Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients”, Clinical and Experimental Health Sciences, vol. 7, no. 3, pp. 85–90, 2017.
ISNAD Genç, Deniz et al. “Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients”. Clinical and Experimental Health Sciences 7/3 (September 2017), 85-90.
JAMA Genç D, Zibandeh N, Uluç K, Koytak PK, Gökalp M, Tanrıdağ T, Akkoç T. Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients. Clinical and Experimental Health Sciences. 2017;7:85–90.
MLA Genç, Deniz et al. “Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients”. Clinical and Experimental Health Sciences, vol. 7, no. 3, 2017, pp. 85-90.
Vancouver Genç D, Zibandeh N, Uluç K, Koytak PK, Gökalp M, Tanrıdağ T, Akkoç T. Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients. Clinical and Experimental Health Sciences. 2017;7(3):85-90.

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