Urinary bladder extracellular matrix hydrogels and matrix-bound vesicles differentially regulate central nervous system neuron viability and axon growth and branching

Anne Faust, Apoorva Kandakatla, Yolandi Van Der Merwe, Tanchen Ren, Luai Huleihel, George Hussey, Juan Diego Naranjo, Scott Johnson, Stephen Badylak, Michael Steketee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Central nervous system neurons often degenerate after trauma due to the inflammatory innate immune response to injury, which can lead to neuronal cell death, scarring, and permanently lost neurologic function. Extracellular matrix bioscaffolds, derived by decellularizing healthy tissues, have been widely used in both preclinical and clinical studies to promote positive tissue remodeling, including neurogenesis, in numerous tissues, with extracellular matrix from homologous tissues often inducing more positive responses. Extracellular matrix hydrogels are liquid at room temperature and enable minimally invasive extracellular matrix injections into central nervous system tissues, before gelation at 37°C. However, few studies have analyzed how extracellular matrix hydrogels influence primary central nervous system neuron survival and growth, and whether central nervous system and non-central nervous system extracellular matrix specificity is critical to neuronal responses. Urinary bladder extracellular matrix hydrogels increase both primary hippocampal neuron survival and neurite growth to similar or even greater extents, suggesting extracellular matrix from non-homologous tissue sources, such as urinary bladder matrix-extracellular matrix, may be a more economical and safer alternative to developing central nervous system extracellular matrices for central nervous system applications. Additionally, we show matrix-bound vesicles derived from urinary bladder extracellular matrix are endocytosed by hippocampal neurons and positively regulate primary hippocampal neuron neurite growth. Matrix-bound vesicles carry protein and RNA cargos, including noncoding RNAs and miRNAs that map to the human genome and are known to regulate cellular processes. Thus, urinary bladder matrix-bound vesicles provide natural and transfectable cargoes which offer new experimental tools and therapeutic applications to study and treat central nervous system neuron injury.

Original languageEnglish
Pages (from-to)1277-1295
Number of pages19
JournalJournal of Biomaterials Applications
Volume31
Issue number9
DOIs
StatePublished - 1 Apr 2017
Externally publishedYes

Keywords

  • Extracellular matrix
  • axon growth
  • hippocampal neuron
  • matrix bound vesicles
  • microglia
  • neuroprotection

Fingerprint

Dive into the research topics of 'Urinary bladder extracellular matrix hydrogels and matrix-bound vesicles differentially regulate central nervous system neuron viability and axon growth and branching'. Together they form a unique fingerprint.

Cite this