Elevation of lysosomal pH in RPE cells interferes with the degradation of outer segments and may contribute to the pathologies associated with A2E. Pharmacologic elevation of cAMP can restore an acid pH and improve degradative function.

Rationale Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, and regenerative capacity of hCPCs. Rejuvenation of senescent hCPCs will improve the outcome of regenerative therapy for a substantial patient population possessing functionally impaired stem cells. Objective Reverse phenotypic and functional senescence of hCPCs by ex vivo modification with Pim-1. Methods and Results C-kit–positive hCPCs were isolated from heart biopsy samples of patients undergoing left ventricular assist device implantation. Growth kinetics, telomere lengths, and expression of cell cycle regulators showed significant variation between hCPC isolated from multiple patients. Telomere length was significantly decreased in hCPC with slow-growth kinetics concomitant with decreased proliferation and upregulation of senescent markers compared with hCPC with fast-growth kinetics. Desirable youthful characteristics were conferred on hCPCs by genetic modification using Pim-1 kinase, including increases in proliferation, telomere length, survival, and decreased expression of senescence markers. Conclusions Senescence characteristics of hCPCs are ameliorated by Pim-1 kinase resulting in rejuvenation of phenotypic and functional properties. hCPCs show improved cellular properties resulting from Pim-1 modification, but benefits were more pronounced in hCPC with slow-growth kinetics relative to hCPC with fast-growth kinetics. With the majority of patients with heart failure presenting advanced age, infirmity, and impaired regenerative capacity, the use of Pim-1 modification should be incorporated into cell-based therapeutic approaches to broaden inclusion criteria and address limitations associated with the senescent phenotype of aged hCPC.

Highlights d A cell organelle, the photosynthetic chromatophore, is modeled in atomistic detail d Segregation of protein complexes tunes chromatophore structure and function d The electrostatic environment of the organelle supports low light-adaptation d Distinct modes of quinone diffusion underpin efficient electron transfer dynamics

The purpose of this study was to investigate whether platelet-rich plasma therapy for early knee osteoarthritis is associated with good clinical outcomes and a change in magnetic resonance imaging (MRI) structural appearances. The design was a prospective cohort study following patients 1 year after platelet-rich plasma therapy for knee osteoarthritis. Twenty-two patients were treated with platelet-rich plasma for early osteoarthritis, confirmed with a baseline MRI. Inclusion criteria were Kellgren grade 0-II with knee pain in patients aged 30 to 70 years. All the patients received a 6-mL platelet-rich plasma injection using the Cascade system. Fifteen subjects underwent clinical assessments at baseline, 1 week, and 1, 3, 6, and 12 months, and MRIs at 1 year. Pain scores significantly decreased, whereas functional and clinical scores increased at 6 months and 1 year from baseline. Qualitative MRIs demonstrated no change per compartment in at least 73% of cases at 1 year.