Cell and Organ Transplantology. 2022; 10(1):26-35.
DOI: 10.22494/cot.v10i1.135

Structural changes of spinal cord tissue of rats with experimental spinal cord injury after the implantation of fibrin matrix associated with neural and mesenchymal progenitor cells

Liubich L.¹, Staino L.¹, Egorova D.¹, Medvediev V.², Oleksenko N.¹, Verbovska S.¹, Pichkur L.¹, Tsymbaliuk V.³

• ¹The State Institution “Romodanov Neurosurgery Institute, National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine
• ²Bohomolets National Medical University, Kyiv, Ukraine
• ³National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Kyiv, Ukraine

Abstract

Spinal cord injury (SCI) is one of the most common severe injuries to the central nervous system, resulting in motor dysfunction and sensory loss. Cell therapy using stem/progenitor cells (SCs/PCs), regenerative biomaterials, tissue engineering technologies and their combinations is a promising area of regenerative medicine for the treatment of this pathology.
The purpose of the research was to study the effect of implantation of fibrin matrix (FM) associated with rat neonatal brain cells (rNBCs) or human mesenchymal stromal cells of Wharton’s jelly (hWJ-MSCs) on the recovery process of rat spinal cord (SC) tissue after lateral hemisection in the lower thoracic-upper lumbar region.
Materials and methods. Four experimental groups were formed: 1) comparison group – SCI without additional treatment (self-recovery); 2) SCI + implantation of cell-free FM fragment in the injury area (SCI + FM); 3) SCI + implantation of FM with incorporated hWJ-MSCs (1·10⁶/ml) in the injury area (SCI + FM + hWJ-MSCs), 4) SCI + implantation of FM with incorporated rNBCs (1·10⁶/ml) in the injury area (SCI + FM + rNBCs). The fragments of the SC tissue for morphological examination were obtained in the long-term period (7-9 months) after SCI. Serial longitudinal thin 5-7 μm sections of the tissue were prepared and immunohistochemical and morphometric studies were performed.
Results. In the long-term period after SCI, the traumatic cavity is replaced by elements of glia and connective tissue. A fragment of cell-free FM implanted in the traumatic area serves as a structural framework that creates a niche for cell migration (gliocytes, neural SCs/PCs (NSCs/NPCs) and, possibly, endogenous regeneration of the defect thanks to its own NSCs/NPCs; in the perifocal zone around the traumatic area, there is an increase in dystrophic changes in neurons, the formation of a gliofibrous capsule. The FM, associated with the hWJ-MSCs and implanted in the traumatic cavity, creates the conditions for hWJ-MSCs survival and, probably, their initial differentiation in the glial direction; incorporated hWJ-MSCs have a neuroprotective effect on the neurons of the perifocal zone, which can serve as a basis for the restoration of SC functions. The FM, associated with the rNBCs and implanted in the traumatic cavity, creates conditions for the structural recovery of SC tissue (replacement by terminally differentiated astrocytes and neurons); incorporated rNBCs have a neuroprotective effect on the neurons of the perifocal zone, which can be the basis for the functional recovery of SC.
Conclusions. Implantation of FM associated with hWJ-MSCs or rNBCs is more effective, compared to the cell-free analogue, in terms of structural recovery of SC and neuroprotective effect after its traumatic transection.

Key words: spinal cord injury; fibrin matrix; neural stem/progenitor cells; multipotent mesenchymal stromal cells; regeneration; neuroprotection

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