title: Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair.
abstract: Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .|2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
authors.forename: Dmitry
authors.initials: D
authors.lastname: Tukmachev
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .|2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
authors.forename: Serhiy
authors.initials: S
authors.lastname: Forostyak
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .|2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Koci
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .|2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
authors.forename: Kristyna
authors.initials: K
authors.lastname: Zaviskova
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .
authors.forename: Irena
authors.initials: I
authors.lastname: Vackova
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .|2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
authors.forename: Karel
authors.initials: K
authors.lastname: Vyborny
authors.affiliation: 3 Department of Neuroscience, Norwegian University of Science and Technology , Trondheim, Norway .|4 John Van Geest Centre for Brain Repair, School of Clinical Neurosciences, University of Cambridge , Cambridge, United Kingdom .
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sandvig
authors.affiliation: 3 Department of Neuroscience, Norwegian University of Science and Technology , Trondheim, Norway .|5 Division of Pharmacology and Clinical Neuroscience, Department of Neurosurgery, Umeå University , Umeå, Sweden .
authors.forename: Axel
authors.initials: A
authors.lastname: Sandvig
authors.affiliation: 6 McGowan Institute for Regenerative Medicine , Pittsburgh, Pennsylvania.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Medberry
authors.affiliation: 6 McGowan Institute for Regenerative Medicine , Pittsburgh, Pennsylvania.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Badylak
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .|2 2nd Medical Faculty, Charles University , Prague, Czech Republic .
authors.forename: Eva
authors.initials: E
authors.lastname: Sykova
authors.affiliation: 1 Institute of Experimental Medicine AS CR , Prague, Czech Republic .
authors.forename: Sarka
authors.initials: S
authors.lastname: Kubinova
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D064593:Heterografts; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy*; D013552:Swine
chemical_list: D020100:Hydrogels