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. 2018 Oct-Dec;8(4):220-226.
doi: 10.4103/ijabmr.IJABMR_436_17.

Therapeutic Effect of Cell Transplantation and Chondroitinase in Rat Spinal Cord Injury

Durai Murugan Muniswami  1 , George Tharion  1
Affiliations

Therapeutic Effect of Cell Transplantation and Chondroitinase in Rat Spinal Cord Injury

Durai Murugan Muniswami et al. Int J Appl Basic Med Res. 2018 Oct-Dec.

Abstract

Background: Spinal cord injury (SCI) leads to permanent functional deficits because the central nervous system lacks the ability for spontaneous repair. Cell therapy strategies offered a hope in neurological repair. The clinical use of human embryonic stem cell transplantation is hampered by scientific and ethical controversies. Olfactory ensheathing cells (OECs)/bone marrow mesenchymal stem cell (MSC) is a promising cell source for autologous neurotransplantation devoid of ethical concerns.

Aim: This study aimed to evaluate the combined therapeutic effect of OEC, MSC, and chondroitinase in SCI rat models.

Materials and methods: Adult female albino Wistar rats were divided into ten groups, n = 6 rats in each group and control (n = 11). T10 level laminectomy was done in anesthetized rats to create drop-weight SCI. Both OEC and MSC were transplanted on the 9th day following SCI as a combined therapy with different dosage of 2 × 105, 5 × 105, 10 × 105, and >10 × 105 at a ratio of 1:1 with/without chondroitinase (0.2 U). One group of SCI rats was treated with chondroitinase alone 0.2 U. Dulbecco's Modified Eagle medium was injected in control rats. The outcome of transplantation was assessed using Basso, Beattie, Bresnahan (BBB) scale and motor-evoked potential studies.

Results: All the treated groups showed hindlimb motor recovery in BBB score except control group (P < 0.05). All the three combinations showed better results than OEC + MSC groups in hindlimb motor recovery. In dose-response relationship, 5- and 10-lakh combinations elicited increased functional recovery than 2- and more than 10-lakh combinations. However, chondroitinase alone demonstrated a highest BBB score than any other groups.

Conclusions: Chondroitinase/cell combinations have a therapeutic beneficial effect in SCI.

Keywords: Basso; Beattie; Bresnahan; chondroitinase; electromyography; mesenchymal stem cells; olfactory ensheathing cells; spinal cord injury; transplantation.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Hindlimb motor recovery mean Basso, Beattie, Bresnahan score of olfactory ensheathing cell + mesenchymal stem cell transplantation. Transplanted groups progressed in Basso, Beattie, Bresnahan score except control group (a). On comparison, there was no statistical significance between the treated groups (P > 0.05). But, treated groups showed significant (P < 0.05) functional recovery as compared to control group (b). Error bars indicate the standard deviations
Figure 2
Figure 2
Hindlimb motor recovery mean Basso, Beattie, Bresnahan score. Error bars indicate the standard deviations
Figure 3
Figure 3
Hindlimb motor recovery mean Basso, Beattie, Bresnahan score of olfactory ensheathing cell + mesenchymal stem cell + chondroitinase transplantation. The treated groups showed an improvement in Basso, Beattie, Bresnahan scores over the period of time (a). Among the treated groups, there is no statistical significance (P > 0.05) in the Basso, Beattie, Bresnahan score (b)
Figure 4
Figure 4
Mean electromyography amplitude of olfactory ensheathing cells + mesenchymal stem cell-transplanted rats. There is a significant increase in electromyography amplitude in 5-lakh, 10-lakh, and more than 10-lakh-transplanted rats as compared to control rats (P < 0.05). Among the treated groups, only 5-lakh combination showed statistical significance (P = 0.05) in comparison with 2-lakh combination group. The results demonstrate the transplant-mediated repair in treated groups of SCI rats
Figure 5
Figure 5
Mean electromyography amplitude of olfactory ensheathing cells + mesenchymal stem cell + chondroitinase-transplanted rats. All the treated groups show variations in electromyography amplitude depending on the regeneration of injured spinal cord. There is a marked increase in the amplitude of chondroitinase alone-treated rats and 10-lakh combination groups, which showed significance (P < 0.05) when compared to control rats. However, no significance was observed among the treated groups (P > 0.05)
Figure 6
Figure 6
Histology of rat spinal cord after injury. Gross tissue of cord with injury epicenter (a). Degenerative cavity size of 2100.9 μm in control (b), and reduced cavity size to 1679 μm in all the three (olfactory ensheathing cell + mesenchymal stem cell + chondroitinase) treated spinal cords (c). scale bar = 20 μm. Longitudinal section of spinal cord showing white matter (d-g) degenerative (black arrow) and intact fibers (red arrow). Cross-section of spinal cord showing gray matter (h-k), in which there is an increased degeneration in controls than treated spinal cords. scale bar = 3 μm
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