Luồng công việc tích hợp mới cho phép sản xuất và đánh giá chất lượng sâu rộng của các tế bào cơ xương biến đổi đa yếu tố từ các tế bào gốc người

Cellular and Molecular Life Sciences - Tập 79 - Trang 1-17 - 2022
Dinis Faustino1,2, Heinrich Brinkmeier3, Stella Logotheti1,2, Anika Jonitz-Heincke4, Hande Yilmaz1,2, Isil Takan5,6, Kirsten Peters7, Rainer Bader4, Hermann Lang8, Athanasia Pavlopoulou5,6, Brigitte M. Pützer1,2, Alf Spitschak1,2
1Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock, Germany
2Department Life, Light and Matter, University of Rostock, Rostock, Germany
3Institute of Pathophysiology, University Medicine Greifswald, Greifswald, Germany
4Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany
5Izmir Biomedicine and Genome Center (IBG), Izmir, Turkey
6İzmir International Biomedicine and Genome Institute, Dokuz Eylül University, İzmir, Turkey
7Department of Cell Biology, Rostock University Medical Center, Rostock, Germany
8Department of Operative Dentistry and Periodontology, Rostock University Medical Centre, Rostock, Germany

Tóm tắt

Kỹ thuật tạo ra mô cơ xương nhằm mục đích tạo ra các chất thay thế sinh học nhằm phục hồi, duy trì hoặc cải thiện chức năng cơ bình thường; tuy nhiên, chất lượng của các tế bào được sản xuất bởi các quy trình hiện tại vẫn không đầy đủ. Trong nghiên cứu này, chúng tôi đã phát triển một quy trình dựa trên nhiều yếu tố kết hợp biểu hiện MYOD do adenovector (AdV) trung gian, điều trị bằng ức chế phân tử nhỏ và yếu tố tăng trưởng, cùng với kích thích xung điện (EPS) để tái lập trình hiệu quả các loại tế bào gốc sinh đa năng nguồn gốc người thành các tế bào cơ xương (SMCs) có chức năng sinh lý. Quy trình này được bổ sung thông qua một quy trình in silico mới cho phép ước lượng sâu và có khả năng tối ưu hóa chất lượng của mô cơ được tạo ra, dựa trên transcriptome của các tế bào đã chuyển hóa. Chúng tôi cũng đã tiến hành đo điện thế (patch-clamp) các tế bào SMC kiểu hình để liên kết các đặc tính sinh điện của chúng với việc tái lập trình transcriptome. Tóm lại, chúng tôi đã thiết lập một phương pháp toàn diện và năng động tại điểm giao thoa của công nghệ dựa trên vector virus, sinh thông tin và sinh lý điện, nhằm tạo ra các tế bào cơ xương chất lượng cao và có thể dẫn dắt các chu trình lặp lại để cải thiện các quy trình myo-phân biệt.

Từ khóa

#tế bào cơ xương #tế bào gốc #kỹ thuật sinh học #điều trị yếu tố tăng trưởng #tái lập trình tế bào #điện sinh lý

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