Effects of Different Doses of Mesenchymal Stem Cells on Functional Recovery After Compressive Spinal-Cord Injury in Mice

•Mesenchymal cells were injected intraperitoneally at three different doses after SCI.•They reached the lesion 24 h after transplantation and survived up to 8 weeks.•All three tested doses of cell transplantation led to morphological and functional recovery.•Transplanted groups showed higher levels of BDNF, NT-3 and NT-4.•Injection of 8 × 105 cells led to better morphological and locomotor results. Despite advances in technology and rehabilitation, no effective therapies are available for patients with SCI, which remains a major medical challenge. This study compared the efficacy of 3 different doses of mesenchymal stem cells (MSCs) administered by intraperitoneal injection as a therapeutic strategy for compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal-cord compression for 1 min with a 30-g vascular clip. The animals received an intraperitoneal (i.p.) injection of MSCs (8 × 104, 8 × 105 or 8 × 106 in 500 μl) or DMEM (500 μl), one week after SCI. The cells of the three MSC doses administered i.p. were able to migrate to the injury site, increase local expression of trophic factors, and enhance fiber sparing and/or regeneration, accompanied by substantial improvement in locomotor performance. Cell transplantation at 8 × 105 density showed the best therapeutic potential, leading to significant tissue and functional improvements compared to the other two doses. These findings indicate that i.p. application of MSCs at the density of 8 × 105 yielded the best results, suggesting that this dose is a good choice for SCI treatment.