Cell and Organ Transplantology. 2025; 13(2):e2025132186.
DOI: 10.22494/cot.v13-2.186
Effect of implantation of a PHPMA hydrogel containing human mesenchymal stromal cells of different origins on hindlimb locomotor function recovery in rats with spinal cord injury
Sahaidak V.1
, Rybachuk O.2,3, Melikov Z.4, Medvediev V.1
- 1O. O. Bogomolets National Medical University, Kyiv, Ukraine
- 2O. O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
- 3M. D. Strazhesko National Scientific Center of Cardiology, Clinical and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Institute of Genetic and Regenerative Medicine, Kyiv, Ukraine
- 4A. P. Romodanov State Institute of Neurosurgery, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Abstract
Spinal cord injury is a relatively common type of trauma under combat conditions and, in addition to an increased risk of mortality, in most cases results in impairments of motor and other functions. Restorative treatment of this injury remains one of the most challenging problems in medicine, and its solution is associated with the use of bioengineered implants in combination with stem cells capable of promoting regenerative axonal growth into the denervated regions of the spinal cord.
Objective. To determine the effect of implantation of a PHPMA hydrogel populated with human mesenchymal stem/stromal cells (MSCs) of different origins on hindlimb locomotor function recovery in rats after experimental spinal cord injury.
Materials and methods. Spinal cord injury was modelled in 70 adult male outbred albino rats aged 3-4 months by left-sided excision of a fragment corresponding to one half of the spinal cord cross-section at the thoracolumbar level. For implantation into the injury site, PHPMA hydrogel (HG) or hydrogel populated with MSCs derived from the wall of the human umbilical artery (MSC-UA) or from derma (MSC-Dr) were used. The control group consisted of animals with spinal cord injury model that received no treatment. Locomotor activity and spasticity in the paretic limb were assessed on days 7 and 14 and subsequently monthly for up to 4 months post-injury using the Basso-Beattie-Bresnahan (BBB) scale and the Ashworth scale, respectively.
Results. Four months after injury, the highest motor function scores were observed in the MSC-UA group, the lowest – in the MSC-Dr group, and intermediate values – in the other groups. Significant differences were detected between the control and MSC-UA groups and between the MSC-UA and MSC-Dr groups (p < 0.05). A significant increase in motor function score in the control group was observed during the first 2 months after injury, in the HG group – during the first month, and in the MSC-Dr and MSC-UA groups – throughout the entire 4-month observation period.
Four months after injury modelling, the highest spasticity scores were observed in the MSC-Dr group, whereas the lowest were observed in the control and MSC-UA groups; statistically significant differences were found only between the MSC-UA and MSC-Dr groups (p < 0.02). In addition, a significant negative correlation between individual motor function and spasticity scores was identified in all groups, with the strongest correlation in the MSC-Dr and SCI groups.
Conclusion. Implantation of PHPMA hydrogel populated with human umbilical artery-derived MSCs into the spinal cord defect in rats promotes improved recovery of locomotor function in the paretic hindlimb at 4 months of follow-up. However, it does not exert a significant effect on spasticity. The use of cell-free hydrogel or hydrogel seeded with dermal MSCs did not result in an improvement in locomotor activity or spasticity of the paretic hindlimb in rats.
Key words: spinal cord injury; PHPMA hydrogel; mesenchymal stem/stromal cells; hindlimb locomotor function; spasticity
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