Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for genetically-modified fibroblasts

PLoS One. 2017 Apr 5;12(4):e0174860. doi: 10.1371/journal.pone.0174860. eCollection 2017.

Abstract

Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid) (PLGA) scaffolds (Vicryl & Ethisorb) as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days) of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF165) and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.

MeSH terms

  • Cell Adhesion
  • Cell Engineering
  • Cell Line
  • Cell Proliferation
  • Fibroblasts / physiology*
  • Genetic Engineering
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Lactic Acid / chemistry*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tissue Scaffolds*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Green Fluorescent Proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid

Grants and funding

This work was partly supported by a grant to Dr. Ziyang Zhang from National Natural Science Foundation of China (Grant No. No. 81401538). This study was also partly supported by an unrestricted the grant of Johnson & Johnson Medical GmbH, Norderstedt, Germany. Johnson & Johnson Medical GmbH provided support in the form of salaries for author MG, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.