Öz
Giriş: Birkaç ülke, doku onarımı ve anti-inflamatuar mekanizmalar yoluyla terapötik etkilerini göz önünde bulundurarak, Koronavirüs-19 (COVID-19) hastalarını tedavi etmek için klinik deneylerde mezenkimal kök hücreleri (MKH) kullanmıştır. Bu çalışma, COVID-19 pnömoni hastalarında MKH uygulamasının klinik ve inflamatuar parametreler ve yaşam beklentisi üzerindeki erken etkilerini araştırmak amaçladı. Gereç ve Yöntem: Türkiye Cumhuriyeti Sağlık Bakanlığı Doku, Organ Nakli ve Diyaliz Hizmetleri Daire Başkanlığı’na başvuran ve 1 Mart 2020 - 1 Mart 2021 tarihleri arasında MKH uygulaması için başvurusu olan COVID-19 pnömonisi (tüm yaş grupları) olan aşılanmamış 164 hastayı geriye dönük olarak inceledik. Bulgular: Kaplan Mayer sağkalım analizi kullanılarak, kırılım yaşı (hayatta kalma riskini önemli ölçüde artıran) 61 yıl olarak bulundu. Kadınlar erkeklere göre 1.56 kat daha fazla ölüm riskine sahipti. Hastaların %68’inde (113/164) komorbidite mevcuttu ve bu komorbiditesi olmayanlara göre ölüm riskini 1,58 kat artırıyordu. Koroner arter hastalığı varlığı ölüm riskini 1,79 kat artırdı. Ayrıca, entübe hastalarda entübe olmayanlara göre ölüm riski 7 kat daha yüksekti (%95 GA: 3.72-13.17). Maalesef hastaların %64’ü (106/164) öldü. Son olarak, MKH sonrası tedavi medyan Sıralı Organ Yetmezliği Değerlendirme Skoru (SOFA) değerlerinde uygulama sırasında, 3, 7, 14. günlerde ve sonuna kadar (taburcu/ölüm) istatistiksel olarak anlamlı bir artış oldu. Sonuç: Bu çalışma aşılanmamış hastalarla yapılmıştır ve COVID-19 ile ilişkili pnömoni için MKH tedavisi yeterince etkili değildir.
Anahtar Kelimeler
Koronavirüs COVID-19 mezenkimal kök hücre mortalite sağ kalım
Kaynakça
- 1. Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2 - Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis 2020;11(2):216-28. google scholar
- 2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020;395(10223):497-506 google scholar
- 3. Galipeau J, Sensebe L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell 2018;22(6):824-33. google scholar
- 4. Bernardo ME, Fibbe WE. Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation. Cell Stem Cell 2013;13(4):392-402. google scholar
- 5. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One 2010;5:e10088. google scholar
- 6. Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. The Lancet Respiratory Medicine 2015;3(1):24-32. google scholar
- 7. Hayes M, Curley G, Laffey JG. Mesenchymal stem cells - a promising therapy for Acute Respiratory Distress Syndrome. F1000 Med Rep 2012;4:2. doi: 10.3410/M4-2. google scholar
- 8. Huppert LA, Liu KD, Matthay MA. Therapeutic potential of mesenchymal stromal cells in the treatment of ARDS. Transfusion 2019;59(S1):869-75. google scholar
- 9. Mueller SM, Glowacki J. Age-related decline in the osteogenic potential of human bone marrow cells cultured in threedimensional collagen sponges. J Cell Biochem 2001;82(4):583-90. google scholar
- 10. Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003;33(6):919-26. google scholar
- 11. Mosna F, Sensebe L, Krampera M. Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev 2010;19(10):1449-70. google scholar
- 12. Rojas M, Cardenes N, Kocyildirim E, Tedrow JR, Caceres E, Deans R, et al. Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep. Stem Cell Res Ther 2014;5(2):42. google scholar
- 13. La Francesca S, Ting AE, Sakamoto J, Rhudy J, Bonenfant NR, Borg ZD, et al. Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study. Transplant Res 2014;3:19. google scholar
- 14. Danchuk S, Ylostalo JH, Hossain F, Sorge R, Ramsey A, Bonvillain RW, et al. Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-a-induced protein 6. Stem Cell Res Ther 2011;2(3):27. google scholar
- 15. Matthay MA, Anversa P, Bhattacharya J. Cell therapy for lung diseases. Report from an NIH-NHLBI workshop. Am J Respir Crit Care Med 2012;188(3):370-5. google scholar
- 16. Pati S, Gerber MH, Menge TD, Wataha KA, Zhao Y, Baumgartner JA, et al. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PLoS One 2011; 6(9):e25171. google scholar
- 17. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005;33(2):145-52. google scholar
- 18. Hashmi S, Ahmed M, Murad MH, Litzow MR, Adams RH, Ball LM, et al. Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis. Lancet Haematol 2016;3(1):e45-e52. google scholar
- 19. Kamen DL, Nietert PJ, Wang H, Duke T, Cloud C, Robinson A, et al. CT-04 Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) in patients with systemic lupus erythematosus: results of an open-label phase I study. Lupus 2018;5(Suppl 2):A46-A47. google scholar
- 20. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507-13. google scholar
- 21. Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. et al. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 2013;143(6):1590-98. google scholar
- 22. Li C, Zhao H, Wang B. Challenges for Mesenchymal Stem Cell-Based Therapy for COVID-19. Drug Des Devel Ther 2020;14:3995-4001. google scholar
- 23. Coppin L, Sokal E, Stephenne X. Thrombogenic Risk Induced by Intravascular Mesenchymal Stem Cell Therapy: Current Status and Future Perspectives. Cells 2019;8(10):1160. google scholar
- 24. Kangelaris KN, Ware LB, Wang CY, Janz DR, Zhuo H, Matthay MA, et al. Timing of Intubation and Clinical Outcomes in Adults with Acute Respiratory Distress Syndrome. Crit Care Med 2016;44(1):120-9. google scholar
- 25. Satici C, Demirkol MA, Sargin Altunok E, Gursoy B, Alkan M, Kamat S, et al. Performance of pneumonia severity index and CURB-65 in predicting 30-day mortality in patients with COVID-19. Int J Infect Dis 2020;98:84-9. google scholar
Öz
Objective: Several countries have used mesenchymal stem cells (MSCs) in clinical trials for treating Coronavirus-19 (COVID-19) patients, considering their therapeutic effects through tissue repair and anti-inflammatory mechanisms. This study aimed to investigate the early effects of MSC application in COVID-19 pneumonia patients on clinical and inflammatory parameters and life expectancy. Material and Method: We retrospectively analyzed 164 unvaccinated patients with COVID-19 pneumonia (all age groups) who had applied to the Republic of Turkiye, Ministry of Health, Department of Tissue, Organ Transplantation, and Dialysis Services and received the MSC application from March 1, 2020 to March 1, 2021. Results: Using the Kaplan Mayer survival analysis, the cut-off age (which significantly increased the survival risk) was found to be 61 years. Females had a 1.56 times higher risk of death than males. Sixty-eight percent (113/164) of the patients had a comorbidity, which increased the risk of death by 1.58 times compared to those without any comorbidity. The presence of coronary artery disease increased the risk of death by 1.79 times. Further, the risk of death was 7 times higher in intubated patients than in those who were not (95% CI: 3.72–13.17). Unfortunately, 64% (106/164) of the patients died. Lastly, there was a statistically significant increase in the post-MSC treatment median Sequential Organ Failure Assessment Score (SOFA) score values at the time of application, on days 3, 7, 14, and until the end (discharge/exitus). Conclusion: This study was conducted with unvaccinated patients and MSC treatment for COVID-19-related pneumonia is not adequately effective.
Anahtar Kelimeler
Coronavirus COVID-19 mesenchymal stem cell mortality survival
Kaynakça
- 1. Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ACE2 - Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging Dis 2020;11(2):216-28. google scholar
- 2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020;395(10223):497-506 google scholar
- 3. Galipeau J, Sensebe L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell 2018;22(6):824-33. google scholar
- 4. Bernardo ME, Fibbe WE. Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation. Cell Stem Cell 2013;13(4):392-402. google scholar
- 5. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One 2010;5:e10088. google scholar
- 6. Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. The Lancet Respiratory Medicine 2015;3(1):24-32. google scholar
- 7. Hayes M, Curley G, Laffey JG. Mesenchymal stem cells - a promising therapy for Acute Respiratory Distress Syndrome. F1000 Med Rep 2012;4:2. doi: 10.3410/M4-2. google scholar
- 8. Huppert LA, Liu KD, Matthay MA. Therapeutic potential of mesenchymal stromal cells in the treatment of ARDS. Transfusion 2019;59(S1):869-75. google scholar
- 9. Mueller SM, Glowacki J. Age-related decline in the osteogenic potential of human bone marrow cells cultured in threedimensional collagen sponges. J Cell Biochem 2001;82(4):583-90. google scholar
- 10. Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003;33(6):919-26. google scholar
- 11. Mosna F, Sensebe L, Krampera M. Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev 2010;19(10):1449-70. google scholar
- 12. Rojas M, Cardenes N, Kocyildirim E, Tedrow JR, Caceres E, Deans R, et al. Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep. Stem Cell Res Ther 2014;5(2):42. google scholar
- 13. La Francesca S, Ting AE, Sakamoto J, Rhudy J, Bonenfant NR, Borg ZD, et al. Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study. Transplant Res 2014;3:19. google scholar
- 14. Danchuk S, Ylostalo JH, Hossain F, Sorge R, Ramsey A, Bonvillain RW, et al. Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-a-induced protein 6. Stem Cell Res Ther 2011;2(3):27. google scholar
- 15. Matthay MA, Anversa P, Bhattacharya J. Cell therapy for lung diseases. Report from an NIH-NHLBI workshop. Am J Respir Crit Care Med 2012;188(3):370-5. google scholar
- 16. Pati S, Gerber MH, Menge TD, Wataha KA, Zhao Y, Baumgartner JA, et al. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PLoS One 2011; 6(9):e25171. google scholar
- 17. Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 2005;33(2):145-52. google scholar
- 18. Hashmi S, Ahmed M, Murad MH, Litzow MR, Adams RH, Ball LM, et al. Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis. Lancet Haematol 2016;3(1):e45-e52. google scholar
- 19. Kamen DL, Nietert PJ, Wang H, Duke T, Cloud C, Robinson A, et al. CT-04 Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cells (MSCs) in patients with systemic lupus erythematosus: results of an open-label phase I study. Lupus 2018;5(Suppl 2):A46-A47. google scholar
- 20. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507-13. google scholar
- 21. Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. et al. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 2013;143(6):1590-98. google scholar
- 22. Li C, Zhao H, Wang B. Challenges for Mesenchymal Stem Cell-Based Therapy for COVID-19. Drug Des Devel Ther 2020;14:3995-4001. google scholar
- 23. Coppin L, Sokal E, Stephenne X. Thrombogenic Risk Induced by Intravascular Mesenchymal Stem Cell Therapy: Current Status and Future Perspectives. Cells 2019;8(10):1160. google scholar
- 24. Kangelaris KN, Ware LB, Wang CY, Janz DR, Zhuo H, Matthay MA, et al. Timing of Intubation and Clinical Outcomes in Adults with Acute Respiratory Distress Syndrome. Crit Care Med 2016;44(1):120-9. google scholar
- 25. Satici C, Demirkol MA, Sargin Altunok E, Gursoy B, Alkan M, Kamat S, et al. Performance of pneumonia severity index and CURB-65 in predicting 30-day mortality in patients with COVID-19. Int J Infect Dis 2020;98:84-9. google scholar
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 28 Şubat 2023 |
| Gönderilme Tarihi | 2 Ocak 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 6 Sayı: 1 |
