Academic Journal
Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited
| العنوان: | Macromolecular Crowding as a Tool to Screen Anti-fibrotic Drugs: The Scar-in-a-Jar System Revisited |
|---|---|
| المؤلفون: | Nataly Puerta Cavanzo, Emilia Bigaeva, Miriam Boersema, Peter Olinga, Ruud A. Bank |
| المصدر: | Frontiers in Medicine, Vol 7 (2021) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | macromolecular crowding, drug testing, fibrosis, collagen, myofibroblast, Medicine (General), R5-920 |
| الوصف: | An unsolved therapeutic problem in fibrosis is the overproduction of collagen. In order to screen the effect of anti-fibrotic drugs on collagen deposition, the Scar-in-a-Jar approach has been introduced about a decade ago. With macromolecular crowding a rapid deposition of collagen is seen, resulting in a substantial decrease in culture time, but the system has never been tested in an adequate way. We therefore have compared six different macromolecular crowders [Ficoll PM 70 (Fc70), Ficoll PM 400 (Fc400), a mixture of Ficoll 70 and 400 (Fc70/400), polyvinylpyrrolidone 40 (PVP40), polyvinylpyrrolidone 360 (PVP360), neutral dextran 670 (ND670), dextran sulfate 500 (DxS500), and carrageenan (CR)] under profibrotic conditions (addition of TGFβ1) with primary human adult dermal fibroblasts in the presence of 0.5 and 10% FBS. We found that (1) collagen deposition and myofibroblast formation was superior with 0.5% FBS, (2) DxS500 and CR results in an aberrant collagen deposition pattern, (3) ND670 does not increase collagen deposition, and (4) CR, DxS500, and Fc40/700 affected important phenotypical properties of the cells when cultured under pro-fibrotic conditions, whereas PVP40 and PVP360 did less or not. Because of viscosity problems with PVP360, we conclude that PVP40 is the most optimal crowder for the screening of anti-fibrotic drugs. Finally, the effect of various concentrations of Imatinib, Galunisertib, Omipalisib or Nintedanib on collagen deposition and myofibroblast formation was tested with PVP40 as the crowder. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2296-858X |
| Relation: | https://www.frontiersin.org/articles/10.3389/fmed.2020.615774/full; https://doaj.org/toc/2296-858X; https://doaj.org/article/b26db37c766342768d57a216cf62e413 |
| DOI: | 10.3389/fmed.2020.615774 |
| الاتاحة: | https://doi.org/10.3389/fmed.2020.615774 https://doaj.org/article/b26db37c766342768d57a216cf62e413 |
| رقم الانضمام: | edsbas.8556B9C9 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2296858X |
|---|---|
| DOI: | 10.3389/fmed.2020.615774 |