Journal article
Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation
Journal of neurotrauma, v 41(17-18), pp 2168-2185
01 Sep 2024
PMID: 39078323
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by in vivo recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.
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Details
- Title
- Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation
- Creators
- Samantha J. Thomas - Thomas Jefferson UniversityBiswarup Ghosh - Thomas Jefferson UniversityZhicheng Wang - University of PennsylvaniaMengxi Yang - Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, 3141 Chestnut St,Bossone 7-718, Philadelphia, PA 19104 USAJia Nong - University of PennsylvaniaJenna Severa - Thomas Jefferson UniversityMegan C. Wright - Drexel UniversityYinghui Zhong - Drexel University, School of Biomedical Engineering, Science, and Health SystemsAngelo C. Lepore - Thomas Jefferson University
- Publication Details
- Journal of neurotrauma, v 41(17-18), pp 2168-2185
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 18
- Grant note
- R01NS110385; R01NS079702 / NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001288790000001
- Scopus ID
- 2-s2.0-85201282879
- Other Identifier
- 991021894657204721
UN Sustainable Development Goals (SDGs)
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Source: SDGs in the Output
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences