Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

摘要

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury (SCI) are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells (MSCs) in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T₉ level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups: sham (anesthesia and laminectomy but without compression injury induction), MSC i.p. (intraperitoneal injection of 8 × 105 MSCs in 500 μL of DMEM at 7 days after SCI), MSC i.v. (intravenous injection of 8 × 105 MSCs in 500 μL of DMEM at 7 days after SCI), DMEM i.p. (intraperitoneal injection of 500 μL of DMEM at 7 days after SCI), DMEM i.v. (intravenous injection of 500 μL of DMEM at 7 days after SCI). The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors (brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4) in the spinal cord and improved locomotor performance. Our results indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial outcomes and can be elected as a choice for SCI treatment.