A collagen-based scaffold delivering exogenous microrna-29B to modulate extracellular matrix remodeling.

Abstract

Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of collagen type I after injury. The release of RNA from the scaffold was assessed and its ability to silence collagen type I and collagen type III expression was evaluated in vitro. When primary fibroblasts were cultured with scaffolds doped with miR-29B, reduced levels of collagen type I and collagen type III mRNA expression were observed for up to 2 weeks of culture. When the scaffolds were applied to full thickness wounds in vivo, reduced wound contraction, improved collagen type III/I ratios and a significantly higher matrix metalloproteinase (MMP)-8: tissue inhibitor of metalloproteinase (TIMP)-1 ratio were detected when the scaffolds were functionalized with miR-29B. Furthermore, these effects were significantly influenced by the dose of miR-29B in the collagen scaffold (0.5 versus 5 μg). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.

• Authors: Michael Monaghan, Shane Browne, Katja Schenke-Layland, Abhay Pandit
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 22 Issue 4 Pg. 786-96 (Apr 2014) ISSN: 1525-0024 [Electronic] United States
• PMID: 24402185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type III
• MIRN29a microRNA, human
• MicroRNAs
• RNA, Messenger
• Matrix Metalloproteinase 8

Topics

• Animals
• Collagen Type I (biosynthesis, genetics)
• Collagen Type III (biosynthesis, genetics)
• Extracellular Matrix (genetics, pathology)
• Fibroblasts (cytology, metabolism)
• Humans
• Matrix Metalloproteinase 8 (genetics, metabolism)
• MicroRNAs (administration & dosage, genetics)
• Primary Cell Culture
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Regenerative Medicine
• Tissue Scaffolds