Neuroprotective effects of bone marrow Sca-1+ cells against age-related retinal degeneration in OPTN E50K mice

Glaucoma is characterized by retinal ganglion cell (RGC) death, the underlying mechanisms of which are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal-tension glaucoma (NTG), which directly affects RGCs in the absence of high intraocular pressure and causes severe glaucomatous symptoms in patients. Bone marrow (BM) stem cells have been demonstrated to play a key role in regenerating damaged tissue during ageing and disease through their trophic effects and homing capability. Here, we separated BM stem cells into Sca-1+ and Sca-1- cells and transplanted them into lethally irradiated aged OPTN E50K mice to generate Sca-1+ and Sca-1− chimaeras, respectively. After 3 months of BM repopulation, we investigated whether Sca-1+ cells maximized the regenerative effects in the retinas of NTG model mice with the OPTN E50K mutation. We found that the OPTN E50K mutation aggravated age-related deficiency of neurotrophic factors in both retinas and BM during NTG development, leading to retinal degeneration and BM dysfunction. Sca-1+ cells from young healthy mice had greater paracrine trophic effects than Sca-1− cells and Sca-1+ cells from young OPTN E50K mice. In addition, Sca-1+ chimaeras demonstrated better visual functions than Sca-1− chimaeras and untreated OPTN E50K mice. More Sca-1+ cells than Sca-1− cells were recruited to repair damaged retinas and reverse visual impairment in NTG resulting from high expression levels of neurotrophic factors. These findings indicated that the Sca-1+ cells from young, healthy mice may have exhibited an enhanced ability to repair retinal degeneration in NTG because of their excellent neurotrophic capability.

Florivory by the occupants of phytotelmata in flower parts can decrease host plant fecundity

Some types of plant accumulate liquid in their inflorescences creating phytotelmata. These environments protect the flowers against florivory, although they may be colonized by aquatic or semi-aquatic florivorous insect larvae, whose effects on the fitness of the plants remain unclear. We tested the hypothesis of floral antagonism by the occupants of phytotelmata, which predicts that florivory by the occupants of the phytotelmata represents a cost to the female fitness of the plant, reducing its fecundity. We manipulated experimentally the infestation by three florivores larvae species occupants of phytotelmata in inflorescences of Heliconia spathocircinata (Heliconiaceae) to test for negative direct trophic effects on the fecundity of the flowering and fruiting bracts. We found that the foraging of the hoverfly (Syrphidae) and moth (Lepidoptera) larvae in the inflorescences contributed to a decline in the fecundity of the plant. While the lepidopteran impacted fecundity when foraging in both flowering and fruiting bracts, the syrphid only affected the fruiting bracts, which indicates that the nectar and floral tissue are the principal resource exploited by the hoverfly. By contrast, soldier fly (Stratiomyidae) had a neutral effect on fecundity, while foraging in flowering or fruiting bracts. These findings corroborate our hypothesis, that herbivory by the larval occupants represents cost to the host plant having phytotelmata. The negative influence of this foraging on plant fecundity will nevertheless depend on the consequences of the exploitation of resources, which vary considerably in ephemeral habitats such as the phytotalmanta of flower parts.

Intra-muscular administration of autologous bone marrow mononuclear cells reduces opioid dependency in patients with critical limb threatening ischemia.

Background and Hypothesis Critical limb-threatening ischemia (CLTI) is a severe limitation in perfusion of the lower extremities. It is the most advanced stage of peripheral arterial disease. Characterized by unremitting rest pain and/or gangrene, the CLTI patient population has an excessively high rate of opioid use and addiction. The MOBILE Trial was a Phase II multi-center, double-blinded placebo controlled trial designed to assess the safety and efficacy of autologous bone marrow cells (ABMC) in treating patients with CLTI. Our central hypothesis is that cell therapy may provide trophic effects in the treated limb that may decrease opioid requirements. Project Methods The primary endpoint of the MOBILE Trial was amputation-free survival at 52 weeks. Secondary endpoints included limb perfusion measures, ambulatory function, quality of life (VascuQol), pain assessment with a visual analog score, and opioid requirements, as tabulated by prescriptions reported to us. A post-hoc statistical analysis using ANOVA was conducted to describe changes in pain and quality of life measures along the study, and Fisher’s test to compare the incidence of new opioid prescriptions between treatment groups. Results There were no differences in quality of life and visual analog pain measures between the ABMC and placebo groups (P= 0.42). There was however a 36% decrease in new opioid prescriptions in the ABMC groups as compared to placebo (P = 0.058, HR: -0.44-1.012). This reduction did not correlate with changes in limb perfusion measures, gender, age, diagnosis of diabetes, or Rutherford score. Discussion The results of this analysis demonstrate an effect of ABMC in reducing opioid use in a high-risk addiction patient population. These findings are consistent with other studies assessing mesenchymal stem cells in chronic pain syndromes. The effect of ABMC did not correlate with changes in limb perfusion suggesting other beneficial trophic effects of cells in ischemic induced neuropathies. This discovery suggests a potential therapeutic strategy for reducing opioid dependency.