Systemic Dental Pulp Stem Cell Secretome Therapy in a Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron (MN) disease with no cure. Accumulating evidence indicates ALS involves a complex interaction between central glia and the peripheral immune response and neuromuscular interface. Stem cell secretomes contain various beneficial trophic factors and cytokines, and we recently demonstrated that administration of the secretome of adipose-derived stem cells (ASCs) during early neuromuscular junction (NMJ) denervation in the mutant superoxide dismutase (mSOD1G93A) ALS mouse ameliorated NMJ disruption. In the present study, we hypothesized that administration of dental pulp stem cell secretome in the form of conditioned medium (DPSC-CM) at different stages of disease would promote NMJ innervation, prevent MN loss and extend lifespan. Our findings show that DPSC-CM significantly improved NMJ innervation at postnatal day (PD) 47 compared to vehicle treated mSOD1G93A mice (p < 0.05). During late pre-symptomatic stages (PD70-P91), DPSC-CM significantly increased MN survival (p < 0.01) and NMJ preservation (p < 0.05), while reactive gliosis in the ventral horn remained unaffected. For DPSC-CM treated mSOD1G93A mice beginning at symptom onset, post-onset days of survival as well as overall lifespan was significantly increased compared to vehicle treated mice (p < 0.05). This is the first study to show therapeutic benefits of systemic DPSC secretome in experimental ALS, and establishes a foundation for future research into the treatment effects and mechanistic analyses of DPSC and other stem cell secretome therapies in ALS.

Functional and Histological Gender Comparison of Age-Matched Rats after Moderate Thoracic Contusive Spinal Cord Injury.

Spinal cord injury (SCI) afflicts hundreds of thousands of Americans, and most SCI (∼80%) occurs in males. In experimental animal models, however, many studies used females. Funding agencies like the National Institutes of Health recommend that new proposed studies should include both genders due to variations in gender response to injuries, diseases, and treatments. However, cost and considerations for some animal models, such as SCI, affect investigators in adapting to this recommendation. Research has increased comparing gender effects in various disease and injury models, including SCI. However, most studies use weight-matched animals, which poses issues in comparing results and outcomes. The present study compared histologic and functional outcomes between age-matched male and female Sprague-Dawley rats in a moderate thoracic contusion SCI model. Cresyl violet and eosin staining showed no significant differences in lesion volume between genders after 9 weeks post-SCI (p > 0.05). Luxol fast blue-stained spared myelin was similar between genders, although slightly greater (∼6%) in spared myelin, compared with cord volume (p = 0.044). Glial reactivity and macrophage labeling in the lesion area was comparable between genders, as well. Basso, Beattie, Bresnahan (BBB) functional scores were not significantly different between genders, and Hargreaves thermal hyperalgesia and Gridwalk sensorimotor analyses also were similar between genders, compared with uninjured gender controls. Analysis of covariance showed weight did not influence functional recovery as assessed through BBB (p = 0.65) or Gridwalk assessment (p = 0.63) in this study. In conclusion, our findings suggest age-matched male and female rats recover similarly in a common clinically relevant SCI model.