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Cell therapies using human induced pluripotent stem cell (hiPSC)-derived nephron progenitor cells (NPCs) are expected to ameliorate acute kidney injury (AKI). However, using hiPSC-derived NPCs clinically is a challenge because hiPSCs themselves are tumorigenic. LIN28A, ESRG, CNMD and SFRP2 transcripts have been used as a marker of residual hiPSCs for a variety of cell types undergoing clinical trials. In this study, by reanalyzing public databases, we found a baseline expression of LIN28A, ESRG, CNMD and SFRP2 in hiPSC-derived NPCs and several other cell types, suggesting LIN28A, ESRG, CNMD and SFRP2 are not always reliable markers for iPSC detection. As an alternative, we discovered a lncRNA marker gene, MIR302CHG, among many known and unknown iPSC markers, as highly differentially expressed between hiPSCs and NPCs, by RNA sequencing and quantitative RT-PCR (qRT-PCR) analyses. Using MIR302CHG as an hiPSC marker, we constructed two assay methods, a combination of magnetic bead-based enrichment and qRT-PCR and digital droplet PCR alone, to detect a small number of residual hiPSCs in NPC populations. The use of these in vitro assays could contribute to patient safety in treatments using hiPSC-derived cells.

Recent studies using human pluripotent stem cells (hPSCs) have developed protocols to induce kidney-lineage cells and reconstruct kidney organoids. However, the separate generation of metanephric nephron progenitors (NPs), mesonephric NPs, and ureteric bud (UB) cells, which constitute embryonic kidneys, in in vitro differentiation culture systems has not been fully investigated. Here, we create a culture system in which these mesoderm-like cell types and paraxial and lateral plate mesoderm-like cells are separately generated from hPSCs. We recapitulate nephrogenic niches from separately induced metanephric NP-like and UB-like cells, which are subsequently differentiated into glomeruli, renal tubules, and collecting ducts in vitro and further vascularized in vivo. Our selective differentiation protocols should contribute to understanding the mechanisms underlying human kidney development and disease and also supply cell sources for regenerative therapies.

Objectives: To accumulate evidence that obstacle avoidance training alone is effective in improving the locomotor ability of individuals with stroke. Design: Systematic review and meta-analysis. Setting: MEDLINE, EMBASE, CENTRAL, ICTRP and PEDro were searched for related information until December 2018. Two independent reviewers extracted data. Outcome measurement data were subjected to meta-analyses using random-effects models. Data syntheses were conducted using RevMan V.5.3, and the certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach. Participants: Participants with various types and phases of stroke were included. Intervention: The usual gait training including obstacle avoidance training (interventions of any type, intensity, duration and frequency). Results: Two randomised controlled trials with a total of 49 participants were used as data sources for this study. The obstacle avoidance training (training) group had lower gait speed than the control group (mean difference (MD) 0.03, 95% CI −0.11 to 0.16, p=0.51). Further, the certainty of evidence was very low. The subjective balance ability (Activities-specific Balance Confidence scale) was not significantly different between the training and control groups (MD 6.65, 95% CI −7.59 to 20.89, p=0.36), and it showed very low certainty of evidence. Conclusions: Obstacle avoidance training may have little or no effect on individuals with stroke. The failure to find the effectiveness of obstacle avoidance training alone is possibly attributable to the insufficient amount of training in the intervention and the lack of well-designed studies that measured relevant outcomes. PROSPERO registration number: CRD42017060691.

The objective of this systematic review was to determine whether rehabilitation impacts clinically relevant outcomes among adult patients with sepsis. Randomized controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PEDro, and the World Health Organization International Clinical Trials Platform Search Portal, as well as conference proceedings and reference lists of relevant articles were collected. Two reviewers independently identified randomized controlled trials on the rehabilitation of patients with sepsis, and the two reviewers independently abstracted trial level data including population characteristics, interventions, comparisons, and clinical outcomes. Our primary outcomes were quality of life (QOL), activity of daily living (ADL), and mortality. Our secondary outcomes were length of stay, return to work, muscle strength, delirium, and all adverse events. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We included two trials enrolling 75 patients. The mean difference (95% confidence interval [CI]) of physical function and physical role in QOL measured by SF-36 were 21.10 (95% CI: 6.57–35.63) and 44.40 (95% CI: 22.55–66.05), respectively. Rehabilitation did not significantly decrease intensive care unit (ICU) mortality (risk ratio, 2.02 [95% CI: 0.46–8.91], I² = 0%; n = 75). ICU length of stay and hospital length of stay and muscle strength were not statistically significantly different and no adverse events were reported in both studies. The certainty of the evidence for these outcomes was “very low.” Data on ADL, return to work, and delirium were not available in any of the trials. Rehabilitation of patients with sepsis might not decrease ICU mortality, but might improve QOL. Further, well-designed trials measuring important outcomes will be needed to determi