RT Journal Article
T1 Modeling chronic cervical spinal cord injury in aged rats for cell therapy studies
A1 Martin-Lopez, Maria
A1 Gonzalez-Munoz, Elena
A1 Gomez-Gonzalez, Emilio
A1 Sanchez-Pernaute, Rosario
A1 Marquez-Rivas, Javier
A1 Fernandez-Munoz, Beatriz
K1 SCI
K1 Myelopathy
K1 Pluripotent stem cells
K1 iPSCs
K1 NPCs
K1 Elderly
K1 Advanced therapies
K1 Long-evans
K1 Transplantation
K1 Recovery
K1 Tumors
K1 Fat
AB With an expanding elderly population, an increasing number of older adults will experience spinal cord injury (SCI) and might be candidates for cell-based therapies, yet there is a paucity of research in this age group. The objective of the present study was to analyze how aged rats tolerate behavioral testing, surgical procedures, post-operative complications, intra-spinal cell transplantation and immunosuppression, and to examine the effectiveness of human iPSC-derived Neural Progenitor Cells (IMR90-hiPSCNPCs) in a model of SCI. We performed behavioral tests in rats before and after inducing cervical hemi-contusions at C4 level with a fourth-generation Ohio State University Injury Device. Four weeks later, we injected IMR90-hiPSC-NPCs in animals that were immunosuppressed by daily cyclosporine injection. Four weeks after injection we analyzed locomotor behavior and mortality, and histologically assessed the survival of transplanted human NPCs. As rats aged, their success at completing behavioral tests decreased. In addition, we observed high mortality rates during behavioral training (41.2%), after cervical injury (63.2%) and after cell injection (50%). Histological analysis revealed that injected cells survived and remained at and around the grafted site and did not cause tumors. No locomotor improvement was observed in animals four weeks after IMR90-hiPSC-NPC transplantation. Our results show that elderly rats are highly vulnerable to interventions, and thus large groups of animals must be initially established to study the potential efficacy of cell-based therapies in age-related chronic myelopathies. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PB Elsevier sci ltd
SN 0967-5868
YR 2021
FD 2021-10-12
LK https://hdl.handle.net/10668/24613
UL https://hdl.handle.net/10668/24613
LA en
DS RISalud
RD Apr 4, 2025