measuring 105 ± 1.3 nm were used to deliver the anti-apoptotic gene into rat bone marrow mesenchymal stem cells.
Bcl-2-transfected bone marrow mesenchymal stem cells exhibited high Bcl-2 expression with low toxicity.
Significant improvements in functional recovery were noted in the BMSCs and Bcl-2-BMSCs groups compared to the model group (p< 0.01).
Transplantation of BMSCs and Bcl-2-BMSCs resulted in enhanced neuronal survival and reduced demyelination.
Western blot analyses indicated an increase in proteins linked to neural recovery and a decrease in a protein associated with scar formation in the treatment groups.
Simplified
OBJECTIVE: This study explored a novel therapy for spinal cord injury (SCI) using to deliver the anti-apoptotic gene into rat bone marrow mesenchymal stem cells (BMSCs), followed by transplantation into a rat SCI model to evaluate its potential in promoting neural regeneration and enhancing SCI therapy.
METHODS: BMSCs were isolated and characterized for surface markers and differentiation potential, and transfected with Bcl-2 via cationic liposomes. A rat SCI model was established to assess the therapeutic effects of BMSCs and Bcl-2-BMSCs. Functional recovery was evaluated using the Basso, Beattie, and Bresnahan (BBB) scale and inclined plate test, while histopathology, Western blot, and real-time polymerase chain reaction (RT-PCR) analyses were performed to assess neural recovery. Nissl and myelin staining were used to evaluate neuronal and myelin recovery.
RESULTS: Following successful characterization of BMSCs and the spherical cationic liposomes (105 ± 1.3 nm, 18.65 ± 1.37 mV zeta potential), optimal transfection conditions were identified. Bcl-2-transfected BMSCs expressed high levels of Bcl-2 with low toxicity. In addition, the SCI results showed significant improvements in the BBB and inclined plate scores of rats in the BMSCs and Bcl-2-BMSCs groups compared to the model group (p< 0.01). HE-stained samples demonstrated that the secretion of Bcl-2 and BMSCs plays a crucial role in SC repair. Western blot results revealed an upregulation of proteins associated with neural recovery (Bcl-2, β-tubulin3, MAP2, NF-200, MBP) and a downregulation of the glial scar-associated protein GFAP in both the BMSCs and Bcl-2-BMSCs groups. Furthermore, Nissl staining and myelin staining showed that both the BMSCs and Bcl-2-BMSCs groups exhibited enhanced neuronal survival, inhibition of demyelination, and significant myelin regeneration.
CONCLUSION: Transplantation of Bcl-2-transfected BMSCs represents a highly promising strategy that effectively promotes neural regeneration, inhibits scar formation, reduces demyelination, and enhances functional recovery, highlighting its potential for clinical translation.
Key numbers
11.16
Increase in
Main effect of vs. on functional recovery.
37°
High-dose group recovery angle
score at day 28 for high-dose .
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