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

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.

Human Dental Pulp Cells: A New Source of Cell Therapy in a Mouse Model of Compressive Spinal Cord Injury

Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists andneuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in termsof functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mousemodel of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of theextraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal andmesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 andcompression of the spinal cord with a vascular clip for 1 min. The cells were transplanted 7 days or 28 days afterthe lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. Weperformed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, andultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better whitematterpreservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissueorganization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, inaddition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. Wealso demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functionalanalysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCsmay be feasible candidates for therapeutic intervention after SCI and central nervous system disorders inhumans.

Transplantation of bone-marrow-derived cells into a nerve guide resulted in transdifferentiation into Schwann cells and effective regeneration of transected mouse sciatic nerve.

Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Nevertheless, the functional outcome after peripheral-nerve regeneration is often poor, especially if the nerve injuries occur far from their targets. Aiming to optimize axon regeneration, we grafted bone-marrow-derived cells (BMDCs) into a collagen-tube nerve guide after transection of the mouse sciatic nerve. The control group received only the culture medium. Motor function was tested at 2, 4, and 6 weeks after surgery, using the sciatic functional index (SFI), and showed that functional recovery was significantly improved in animals that received the cell grafts. After 6 weeks, the mice were anesthetized, perfused transcardially, and the sciatic nerves were dissected and processed for transmission electron microscopy and light microscopy. The proximal and distal segments of the nerves were compared, to address the question of improvement in growth rate; the results revealed a maintenance and increase of nerve regeneration for both myelinated and non-myelinated fibers in distal segments of the experimental group. Also, quantitative analysis of the distal region of the regenerating nerves showed that the numbers of myelinated fibers, Schwann cells (SCs) and g-ratio were significantly increased in the experimental group compared to the control group. The transdifferentiation of BMDCs into Schwann cells was confirmed by double labeling with S100/and Hoechst staining. Our data suggest that BMDCs transplanted into a nerve guide can differentiate into SCs, and improve the growth rate of nerve fibers and motor function in a transected sciatic-nerve model.