Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after C5 dorsal column lesion and T12 contusion spinal cord injury in male and female C57BL/6 mice

DOI:10.34945/F5TS33

DATASET CITATION

Dulin J. N., Aceves M., McCreedy D. A. (2023) Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after C5 dorsal column lesion and T12 contusion spinal cord injury in male and female C57BL/6 mice. Open Data Commons for Spinal Cord Injury. ODC-SCI:873 http://doi.org/10.34945/F5TS33

ABSTRACT

STUDY PURPOSE: Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery of motor and sensory functions after SCI, is poorly understood. We transplanted developmentally-restricted spinal cord NPCs, isolated from E11.5-E13.5 mouse embryos, into sites of adult mouse SCI and analyzed graft axon outgrowth, cellular composition, host axon regeneration, and locomotor and thermal sensory behavior.

DATA COLLECTED: Abbreviated Methods: (More detailed information can be found in the Methodology document.) Male and female C57BL/6 mice (18-33 g) were used for this study. Either cervical (C5) dorsal column lesion SCI or thoracic (T12) contusion SCI (50 kdynes, Infinite Horizon impactor device) was performed. Either immediately after SCI (C5 dorsal column lesion groups) or 2 weeks after SCI (T12 contusion groups), mouse spinal cord neural progenitor cells of specific developmental stages or fibrin/thrombin matrix was injected into the lesion site. The specific developmental stages include: E11.5 NPCs, E12.5 NPCs, E13.5 NPCs, E12.5 dorsal NPCs, and E13.5 ventral NPCs. For the animals receiving C5 dorsal column lesion, they were sacrificed at 4 weeks post-transplantation for histological analysis. No behavioral testing was performed on these animals. For the animals receiving T12 contusion, we conducted behavioral assessments both prior to SCI and until 70 days post-SCI, then performed histological assessments of graft survival. Behavioral assessments include open field locomotor (BMS) testing and Hargreaves (thermal sensitivity) testing of hindpaws. BMS was performed at 1, 3, 5, 7 days post-SCI and weekly until 70 DPI. Hargreaves testing was performed weekly at 14-70 DPI.

CONCLUSIONS: -Immunohistochemical analysis showed that the abundance of some subtypes of neurons are significantly different between graft types. -Axon outgrowth is significantly greater in E11.5 grafts than all other groups. -5-HT+ axon regeneration into E11.5 grafts is significantly greater than other graft types. -CGRP+ axon regeneration into E13.5 grafts is significantly greater than other graft types. -There was no effect of any graft type on hindlimb locomotor recovery compared to vehicle (fibrin/thrombin matrix). -Animals with E13.5 grafts exhibited significantly lower thermal latency scores compared to all other treatment groups. Together, these findings indicate that NPC graft cellular composition varies with the developmental stage of donor cells, and that anatomical and behavioral outcomes are influenced by graft type.

KEYWORDS

Spinal Cord Injury; contusion; Neural Stem Cell; CGRP; serotonergic axons; thermal sensitivity; Locomotor function; neural progenitor cell

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DATASET INFO

Contact: Dulin Jennifer (jdulin@bio.tamu.edu)

Lab: Dulin lab

ODC-SCI Accession:873

Records in Dataset: 106

Fields per Record: 47

Last updated: 2023-05-12

Date published: 2023-05-12

Downloads: 6

Files: 2

LICENSE

Creative Commons Attribution License (CC-BY 4.0)

FUNDING AND ACKNOWLEDGEMENTS

National Institutes of Health R01NS116404 (JND); R01NS122961 (DAM), Craig H. Neilsen Foundation 651215 (MA); 546639 (JND), Mission Connect, a program of TIRR Foundation 021-101

CONTRIBUTORS

Dulin, Jennifer N. [ORCID:0000-0001-5767-4290]

Texas A&M University

Aceves, Miriam [ORCID:0000-0002-1778-0213]

Texas A&M University

McCreedy, Dylan A. [ORCID:0000-0003-2413-0793]

Texas A&M University