Bone marrow-derived mesenchymal stromal cell: what next?

Fernanda T Borges,1,2 Marcia Bastos Convento,1 Nestor Schor1,† 1Nephrology Division, Department of Medicine, Universidade Federal de São Paulo, São Paulo, SP, Brazil; 2Interdisciplinary Postgraduate Program in Health Sciences, Universidade Cruzeiro do Sul, São Paulo, SP, Brazil †Professor Nestor Schor passed away on February 2, 2018 Abstract: Bone marrow mesenchymal stromal cell (MSC) is a potential alternative in regenerative medicine and has great potential in many pathologic conditions including kidney disease. Although most of the studies demonstrate MSC efficiency, the regenerative potential may not be efficient in all diseases and patients. Stem cell feasibility is modified by donor characteristics as gender, age, diet, and health status, producing both positive and negative results. The conditioning of MSC can potentiate its effects and modify its culture medium (CM). In current practices, the cell-free treatment is gaining notable attention, while MSC-conditioned CM is being applied and studied in many experimental diseases, including, but not limited to, certain kidney diseases. This may be the next step for clinical trials. Studies in stem cell CM have focused mainly on extracellular vesicles, nucleic acids (mRNA and microRNA), lipids, and proteins presented in this CM. They mediate regenerative effects of MSC in a harmonic manner. In this review, we will analyze the regenerative potential of MSC and its CM as well as discuss some effective techniques for modifying its fractions and improving its therapeutic potential. CM fractions may be modified by hypoxic conditions, inflammation, lipid exposition, and protein growth factors. Other possible mechanisms of action of stem cells are also suggested. In the future, the MSC paracrine effect may be modified to more closely meet each patient’s needs. Keywords: mesenchymal stromal cells, secretome, extracellular vesicles, microRNAs, lipids, growth facto

Normal values for fundus perimetry with the microperimeter MP1.

Purpose: To identify age-stratified normal light sensitivity values for microperimetry (fundus perimetry) and to evaluate the short-term repeatability of the MP1 microperimeter in normal volunteers. Design: Multicenter, prospective, observational study. Participants: One hundred ninety subjects. Methods: One hundred ninety eyes of 190 healthy volunteers (age range, 20\u201375 years) underwent automatic, full-threshold microperimetry of the central field (2020\ub0, 77 stimulated points) with the MP1 microperimeter (Nidek Technologies, Gamagori, Japan). Fixation was documented simultaneously. A subgroup of 10 subjects was retested after 1 hour and 1 week to determine the repeatability of this technique. Main Outcome Measures: By linear regression analyses, light sensitivity values were obtained from 4 fundus areas and were analyzed for differences related to region, age, and, in a subset of subjects, repeat testing over time and right and left eye variability. Short-term repeatability for each area was evaluated by calculating intraclass correlation coefficients. Results: Linear regression analysis showed a significantly greater (P0.0001) mean macular sensitivity of 19.60.5 dB in the 20 to 29 years of age group compared with 18.61.5 dB in the oldest age group of 70 to 75 years. These results were confirmed by the fifth percentile of light sensitivity threshold distribution. Normal and 95% confidence interval age-stratified values were calculated. When results for all 190 subjects were analyzed by region, the superior retinal sector showed significantly lower mean sensitivity values than other sectors (P0.01, Bonferroni test). In a subset of 10 subjects, repeatability of the test performed at 3 separate visits showed consistent values over time in all areas (P0.01, intraclass correlation coefficients). Conclusions: Automatic fundus perimetry with the MP1 microperimeter allows for an accurate, repeatable, topographically specific examination of the retinal threshold in selected retinal areas. These findings are the first extensive database of age-related, normal MP1 microperimetry results available to clinician