Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions

Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue

Severe transaminitis after interferon-ribavirin therapy in HIV/HCV-coinfected patients: influence of a sustained HCV response

EA MERS CT3 Enjeu 3International audienceChronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (+/- 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.123.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis

Mesenchymal Stem Cells and Periodontal Regeneration

The use of mesenchymal stem cell (MSC) therapy offers the potential to develop a completely novel and improved method of periodontal regeneration compared to existing methods. Since the initial demonstration of the presence of MSCs in the periodontal ligament, many recent studies have now demonstrated the potential for the transplantation of MSCs from PDL and other sources to enhance periodontal regenerative outcomes in a variety of animal models. In addition, the recent demonstration of the possible utility of allogeneic MSCs and MSCs derived from inducible pluripotent stem cells may offer new methods of delivering such therapies. Determination of the specific roles that MSCs may play in enhancing regenerative outcomes requires further investigation. The principle of MSC-directed periodontal regenerative therapy is accepted in the field, but extensive investigation is necessary to establish viable, efficacious, and practically applicable human therapies.</p