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Mikroenkapsülasyon Sisteminin Aljinat-Hücre Süspansiyon Yoğunluğuna Bağlı Hızlarının Değerlendirilmesi

Year 2021, Volume: 4 Issue: 3, 87 - 94, 29.09.2021

Abstract

Amaç: Mikroenkapsülasyon tekniği sağlık bilimlerinde ilaç veya hücre gibi terapötik araçların bir kaplayıcı malzeme ile kaplanarak hem taşınımı hem de muhafazasını sağlamak amacıyla kullanılmaktadır. Kaplayıcı materyal olarak doğal olan ve olmayan birçok polimerik malzeme kullanılmaktadır. Bunlar arasında biyouyumluluğu ve yapısal stabilitesinden dolayı ultra saf aljinat avantajlı konumdadır. Bu çalışmada ultra saf aljinat ile paratiroit hücreleri kullanılarak mikroenkapsülasyon için ideal aljinat-hücre süspansiyon oranını, uygun hücre izolasyon metodunu ve mikroenkapsülasyon oluşturmak için kullanılan sistemin en uygun akış hızını belirlemek amaçlanmıştır. Gereç ve Yöntem: Çalışmada dört ayrı paratiroit dokusundan, iki farklı izolasyonla (enzimatik/ mekanik) elde edilen paratiroit hücreleri kullanılmıştır. Hücreler serum fizyolojik ile süspanse hale getirilerek farklı miktarlarda aljinat ile enkapsüle edilmiştir. Sonrasında belirlenen aljinathücre süspansiyon oranları, iki farklı izolasyonla elde edilen paratiroit hücreleri ile farklı akış hızlarında enkapsüle edilerek in vitro olarak morfolojileri ve hücrelerin salgıladığı parathormon miktarı takip edilmiştir. Bulgular: Morfolojik olarak 500μL:200μL (aljinat:hücre süspansiyon hacmi) oranında hazırlanan enkapsüllerin in vitro olarak verimli olduğu belirlenmiştir. Böylelikle %28 oranında aljinat-hücre süspansiyon oranı sabit tutularak; mekanik izolasyonlu hücrelerin kullanıldığı mikroenkapsüllerin morfoloji ve cihazın akış hızına negatif etki oluşturduğu belirlenmiştir. Yalnızca enzimatik hücre izolasyonu yapılan paratiroit hücreleri farklı akış hızlarında morfolojik farklılıklar oluşturmuş ve 2,5mL/dakika hızın yapı, salgıladıkları parathormon ve stabilite açısından verimli oldukları belirlenmiştir. Sonuç: Hücrelerin salgıladığı ürünlerin kapsül alanı dışına ulaşması hücremikroenkapsülasyonunun temel işleyişini oluşturmaktadır. Yapısal stabilitenin korunması, mikroenkapsüle edilen hücrelerin etkin şekilde beslenmesine olanak sağlamalıdır. Ayrıca bu çalışma ile aljinat-hücre süspansiyon oranı, uygun hücre izolasyon metodu ve akış hızı sınırları netleştirilmiştir. Gelecek çalışmalarla belirlenen değerlerin uzun in vitro takiplerinin yapılması gerekmektedir.

Supporting Institution

Bezmialem Vakıf Üniversitesi Bilimsel Araştırma Projeleri

Project Number

20200204

References

  • 1. Yucesan E, Basoglu H., Goncu B, Ozten Kandas N, Ersoy YE, Akbas F, Aysan E. In-vitro optimization of microencapsulated parathyroid cells. Dicle Medical Journal 2017;44(4):373-80.
  • 2. Yücesan E, Göncü BS, Başoğlu H, Özten Kandaş N, Kanımdan E, Akbaş F, Ersoy YE. Aysan E, Experimental Alternative Method for the Treatment of Hypothyroidism: Capsulation of the Thyroid Tissue. Akdeniz Med J 2018;5(3):417-23.
  • 3. Goncu B., Yucesan E. Microencapsulation for Clinical Applications and Transplantation by Using Different Alginates. 2021.
  • 4. Fort A et al. Biohybrid devices and encapsulation technologies for engineering a bioartificial pancreas. Cell Transplant 2008;17(9):997-1003.
  • 5. Jacobs-Tulleneers-Thevissen D et al. Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia 2013;56(7):1605-14.
  • 6. Basta G et al, Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Diabetes Care 2011;34(11): 2406-9.
  • 7. Shin Eric Y et al. Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury. J Am Heart Assoc 2018;7(2): e006949.
  • 8. Yucesan E et al. Microencapsulated parathyroid allotransplantation in the omental tissue. Artif Organs, 2019;43(10):1022-27.
  • 9. Yucesan E et al. Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1-year follow-up. Clin Transplant 2017;31(11): doi:10.1111/ctr.13086.
  • 10. Fukuda S et al. The intraperitoneal space is more favorable than the subcutaneous one for transplanting alginate fiber containing iPSderived islet-like cells. Regen Ther 2019;11:65-72.
  • 11. Omami M et al. Islet Microencapsulation: Strategies and Clinical Status in Diabetes. Curr Diab Rep 2017;17(7):47.
  • 12. Woodhams L, Al-Salami H. The roles of bile acids and applications of microencapsulation technology in treating Type 1 diabetes mellitus. Ther Deliv 2017;8(6):401-9.
  • 13. Long R et al. Co-microencapsulation of BMSCs and mouse pancreatic β cells for improving the efficacy of type I diabetes therapy. Int J Artif Organs 2017;40(4):169-175.
  • 14. Cañibano-Hernández A et al. Alginate Microcapsules Incorporating Hyaluronic Acid Recreate Closer in Vivo Environment for Mesenchymal Stem Cells. Mol Pharm 2017;14(7):2390-9.
  • 15. Hasse C et al, Amitogenic alginates: key to first clinical application of microencapsulation technology. World J Surg 1998;22(7):659-65.
  • 16. Aysan E et al. Parathyroid Allotransplant With a New Technique: A Prospective Clinical Trial. Exp Clin Transplant 2016;14(4):431-5.
  • 17. Aysan E et al. Parathyroid Allotransplant for Persistent Hypocalcaemia: A New Technique Involving Short-Term Culture. Exp Clin Transplant 2016;14(2):238-41.
  • 18. Aysan E et al. Discharging a Patient Treated With Parathyroid Allotransplantation After Having Been Hospitalized for 3.5 Years With Permanent Hypoparathyroidism: A Case Report. Transplant Proc 2019;51(9):3186-8.
  • 19. Brown WH. Parathyroid Implantation in the Treatment of Tetania Parathyreopriva. Ann Surg 1911;53(3):305-17.
  • 20. Hasse C et al. First successful xenotransplantation of microencapsulated human parathyroid tissue in experimental hypoparathyroidism: longterm function without immunosuppression. J Microencapsul 1997;14(5):617-26.
  • 21. Benvenuto LJ, Anderson MR, Arcasoy SM. New frontiers in immunosuppression. J Thorac Dis 2018;10(5):3141-55.
  • 22. Barczynski MF. Golkowski, and I. Nawrot, Parathyroid transplantation in thyroid surgery. Gland Surg 2017;6(5):530-6.
  • 23. Gasperini L, Mano JF, Reis RL. Natural polymers for the microencapsulation of cells. J R Soc Interface 2014;11(100):20140817.

Evaluation of Alginate-Cell Suspension Density by Microencapsulation System’s Flow Rate

Year 2021, Volume: 4 Issue: 3, 87 - 94, 29.09.2021

Abstract

Objective: The microencapsulation technique is mainly used in health sciences to provide both transport and preservation of therapeutic tools, such as drugs or cells, by coating them with a coating material. Naturally occurring and synthetic (non-natural) polymers are widely used as a coating material. Unlike others, the ultrapure alginate is more advantageous due to its high biocompatibility and structural stability. In this study, our aim is to determine the ideal alginatecell suspension ratio for microencapsulation, the appropriate cell isolation method, and the optimum flow rate of the system by using ultra-pure alginate and parathyroid cells. Materials and Methods: In this study, parathyroid cells were obtained from four different parathyroid tissues through two different isolation methods (enzymatic/mechanical). The cells were suspended in an isotonic saline solution and encapsulated with different amounts of ultrapure alginate. Afterward, the determined alginate-cell suspension ratio was microencapsulated with parathyroid cells, and different flow rates, morphology, and the amount of parathyroid hormone secretion were followed in vitro. Results: Morphologically, the ratio of 500μL:200μL (alginate:cell suspension volume) microencapsules was the most stable and efficient group in vitro. By this, the 28% alginate:cell suspension ratio was stabilized. The microencapsulated of the mechanically isolated cells were not found stable morphologically and negatively impacted the flow rate of the system. Particularly, enzymatic isolated parathyroid cells have high structural stability without showing equal distribution; however, only the 2.5 mL/minutes flow rate provided the equal distribution and stable parathormone release. Conclusion: The basic principle of cell-microencapsulation is that the released products reach the outside of the capsule area. In addition, maintaining structural stability allows access to the nutrients to pass easily for the cells. In this study, the alginate-cell suspension ratio, favorable cell isolation method, and flow rate limits were clarified. An in vitro long-term, follow-up should be evaluated by future studies.

Project Number

20200204

References

  • 1. Yucesan E, Basoglu H., Goncu B, Ozten Kandas N, Ersoy YE, Akbas F, Aysan E. In-vitro optimization of microencapsulated parathyroid cells. Dicle Medical Journal 2017;44(4):373-80.
  • 2. Yücesan E, Göncü BS, Başoğlu H, Özten Kandaş N, Kanımdan E, Akbaş F, Ersoy YE. Aysan E, Experimental Alternative Method for the Treatment of Hypothyroidism: Capsulation of the Thyroid Tissue. Akdeniz Med J 2018;5(3):417-23.
  • 3. Goncu B., Yucesan E. Microencapsulation for Clinical Applications and Transplantation by Using Different Alginates. 2021.
  • 4. Fort A et al. Biohybrid devices and encapsulation technologies for engineering a bioartificial pancreas. Cell Transplant 2008;17(9):997-1003.
  • 5. Jacobs-Tulleneers-Thevissen D et al. Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia 2013;56(7):1605-14.
  • 6. Basta G et al, Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Diabetes Care 2011;34(11): 2406-9.
  • 7. Shin Eric Y et al. Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury. J Am Heart Assoc 2018;7(2): e006949.
  • 8. Yucesan E et al. Microencapsulated parathyroid allotransplantation in the omental tissue. Artif Organs, 2019;43(10):1022-27.
  • 9. Yucesan E et al. Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1-year follow-up. Clin Transplant 2017;31(11): doi:10.1111/ctr.13086.
  • 10. Fukuda S et al. The intraperitoneal space is more favorable than the subcutaneous one for transplanting alginate fiber containing iPSderived islet-like cells. Regen Ther 2019;11:65-72.
  • 11. Omami M et al. Islet Microencapsulation: Strategies and Clinical Status in Diabetes. Curr Diab Rep 2017;17(7):47.
  • 12. Woodhams L, Al-Salami H. The roles of bile acids and applications of microencapsulation technology in treating Type 1 diabetes mellitus. Ther Deliv 2017;8(6):401-9.
  • 13. Long R et al. Co-microencapsulation of BMSCs and mouse pancreatic β cells for improving the efficacy of type I diabetes therapy. Int J Artif Organs 2017;40(4):169-175.
  • 14. Cañibano-Hernández A et al. Alginate Microcapsules Incorporating Hyaluronic Acid Recreate Closer in Vivo Environment for Mesenchymal Stem Cells. Mol Pharm 2017;14(7):2390-9.
  • 15. Hasse C et al, Amitogenic alginates: key to first clinical application of microencapsulation technology. World J Surg 1998;22(7):659-65.
  • 16. Aysan E et al. Parathyroid Allotransplant With a New Technique: A Prospective Clinical Trial. Exp Clin Transplant 2016;14(4):431-5.
  • 17. Aysan E et al. Parathyroid Allotransplant for Persistent Hypocalcaemia: A New Technique Involving Short-Term Culture. Exp Clin Transplant 2016;14(2):238-41.
  • 18. Aysan E et al. Discharging a Patient Treated With Parathyroid Allotransplantation After Having Been Hospitalized for 3.5 Years With Permanent Hypoparathyroidism: A Case Report. Transplant Proc 2019;51(9):3186-8.
  • 19. Brown WH. Parathyroid Implantation in the Treatment of Tetania Parathyreopriva. Ann Surg 1911;53(3):305-17.
  • 20. Hasse C et al. First successful xenotransplantation of microencapsulated human parathyroid tissue in experimental hypoparathyroidism: longterm function without immunosuppression. J Microencapsul 1997;14(5):617-26.
  • 21. Benvenuto LJ, Anderson MR, Arcasoy SM. New frontiers in immunosuppression. J Thorac Dis 2018;10(5):3141-55.
  • 22. Barczynski MF. Golkowski, and I. Nawrot, Parathyroid transplantation in thyroid surgery. Gland Surg 2017;6(5):530-6.
  • 23. Gasperini L, Mano JF, Reis RL. Natural polymers for the microencapsulation of cells. J R Soc Interface 2014;11(100):20140817.
There are 23 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Ömer Faruk Düzenli 0000-0002-2938-711X

Beyza Göncü 0000-0001-6026-8218

Emrah Yücesan This is me 0000-0003-4512-8764

Harika Salepçioğlu Kaya This is me 0000-0001-8557-8140

Yeliz Emine Ersoy This is me 0000-0002-5028-6436

Adem Akçakaya This is me 0000-0003-3116-7033

Project Number 20200204
Publication Date September 29, 2021
Submission Date April 29, 2021
Published in Issue Year 2021 Volume: 4 Issue: 3

Cite

MLA Düzenli, Ömer Faruk et al. “Mikroenkapsülasyon Sisteminin Aljinat-Hücre Süspansiyon Yoğunluğuna Bağlı Hızlarının Değerlendirilmesi”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, vol. 4, no. 3, 2021, pp. 87-94.