Induced pluripotent stem cell- derived Neuronal Precursors Ameliorate Sensory and Motor Ability in Non-Human Primates Suffering Spinal Cord Injury

Document Type : Original Research

Authors
R. Jabbari 1
M. Hajinasrollah 2
S. Mohitmafi 3
B. Rafiei 4
H. Ghanaati 4
1 Department of Neurosurgical Science, Loghman Hakim Medical Center, Shahid Behshti University of Medial Sciences, Tehran, Iran.
2 Animal Care Facility, Reproductive Biomedicine Research Center, ROYAN Institute for Biotechnology, ACECR, Tehran, Iran,
3 Department of Veterinary Medicine, Karaj branch, Islamic Azad University, Karaj, Iran
4 Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: The sensory and mobility failure associated with spinal cord injury (SCI) is desperately complicated due to the pathological events that occur sequentially in consequent to the injury.

Objectives: Herein, we applied neural stem cells, derived from human iPSCs (hiPSC-NSCs), to ameliorate the behavioral complications of contusive SCI in Rhesus monkeys, in sub-acute phase.

Methods: hiPSC-NSCs were maintained and characterized in vitro for general NSCs as well as hind-limb specific gene and protein expression prior to transplantation. Moreover, Masson's trichrome staining (MTS) in addition to luxol fast blue (LFB) were performed to determine the fibrotic scar reduction and myelination respectively. Tarlov’s scale were utilized to score the motor improvement, plus, sensory perception evaluation throughout six months following the injury.

Results: hiPSC-NSCs were identified to own NSCs’ exclusive properties in vitro by SOX2, DCX and NESTIN in addition to NESTIN , PAX6 , SOX1 , HOXA2 and HOXB2 protein and gene expression. Additionally, hiPSC-NSCs caused remarkable depletion in fibrotic scar and enhance myelination; spinal shock, sensory responses, reflexes and motor function were improved over six months.

Conclusions: Our findings suggest that hiPSC-NSCs lead to promising recovery after SCI, therefore, this source of NSCs provide a therapeutic potential in clinical studies.

Keywords

Subjects

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Pathobiology Reserach
Volume 26, Issue 4
July 2023
Pages 77-85