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Background and Purpose: Stem cell–based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell–based therapy in patients with ischemic stroke. Methods: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. Results: For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. Conclusions: Stem cell–based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01716481.

Introduction: Simultaneous increase of myofibrils and mitochondria is a key process of cardiomyocyte differentiation from pluripotent stem cells (PSCs). Specifically, development of mitochondrial oxidative energy metabolism in cardiomyocytes is essential to providing the beating function. Although previous studies reported that mitochondrial oxidative metabolism have some correlation with the differentiation of cardiomyocytes, the mechanism by which mitochondrial oxidative metabolism is regulated and the link between cardiomyogenesis and mitochondrial function are still poorly understood. Methods: We performed transcriptome analysis on cells at specific stages of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected highly upregulated mitochondrial metabolic genes at cardiac lineage commitment and time-dependent manner during cardiomyocyte differentiation and identified the protein-protein interaction network connecting between mitochondrial metabolic and cardiac developmental genes. Results: We found several mitochondrial metabolic regulatory genes at cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpa, Cdkn2a in mESC-derived cells and CCK, NOS3 in hiPSC-derived cells) and time-dependent manner during cardiomyocyte differentiation (Eno3, Pgam2, Cox6a2, Fabp3 in mESC-derived cells and PGAM2, SLC25A4 in hiPSC-derived cells). Notably, mitochondrial metabolic proteins are highly interacted with cardiac developmental proteins time-dependent manner during cardiomyocyte differentiation rather than cardiac lineage commitment. Furthermore, mitochondrial metabolic proteins are mainly interacted with cardiac muscle contractile proteins rather than cardiac transcription factors in cardiomyocyte. Conclusions: Mitochondrial metabolism is critical at cardiac maturation rather than cardiac lineage commitment.

Simultaneous increase of myofibrils and mitochondria is a key process of cardiomyocyte differentiation from pluripotent stem cells (PSCs). Specifically, development of mitochondrial oxidative energy metabolism in cardiomyocytes is essential to providing the beating function. Although previous studies reported that mitochondrial oxidative metabolism have some correlation with the differentiation of cardiomyocytes, the mechanism by which mitochondrial oxidative metabolism is regulated and the link between cardiomyogenesis and mitochondrial function are still poorly understood. In the present study, we performed transcriptome analysis on cells at specific stages of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected highly upregulated mitochondrial metabolic genes at cardiac lineage commitment and time-dependent manner during cardiomyocyte differentiation and identified the protein-protein interaction network connecting between mitochondrial metabolic and cardiac developmental genes. We found several mitochondrial metabolic regulatory genes at cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpa, Cdkn2a in mESC-derived cells and CCK, NOS3 in hiPSC-derived cells) and time-dependent manner during cardiomyocyte differentiation (Eno3, Pgam2, Cox6a2, Fabp3 in mESC-derived cells and PGAM2, SLC25A4 in hiPSC-derived cells). Notably, mitochondrial metabolic proteins are highly interacted with cardiac developmental proteins time-dependent manner during cardiomyocyte differentiation rather than cardiac lineage commitment. Furthermore, mitochondrial metabolic proteins are mainly interacted with cardiac muscle contractile proteins rather than cardiac transcription factors in cardiomyocyte. Therefore, mitochondrial metabolism is critical at cardiac maturation rather than cardiac lineage commitment.

Objective To re-evaluate the utility of the conventional criteria for clinical chorioamnionitis in the prediction of early-onset neonatal sepsis (EONS) in preterm birth. Design Retrospective cohort study. Setting Seoul, Republic of Korea. Sample A total of 1468 singleton births between 24 and 34 weeks due to preterm labour (n = 713) or preterm prelabour rupture of membranes (n = 755). Method We evaluated three diagnostic categories of clinical chorioamnionitis: Criteria 1, conventional criteria; Criteria 2, combination of any three conventional parameters without prerequisite fever; Criteria 3, Criteria 1 plus positive maternal C-reactive protein and neutrophil left-shift into minor criteria. EONS included proven or suspected sepsis within 7 days following birth. Neonatal morbidity and mortality of EONS were also reviewed. Main outcome measures Diagnostic performance of three combinations. Results The prevalence of EONS was 13.8%. Among 203 cases of EONS, maternal manifestation of clinical chorioamnionitis by criteria 1 was evident in only one out of seven, indicating 15.3% sensitivity for EONS prediction. However, with application of criteria 2, sensitivity significantly increased to 34.0%, while compromising specificity from 92.3% to 78.7%. Criteria 3 showed similar diagnostic performance compared with criteria 1 (sensitivity 16.7%, specificity 91.6%). Overall, neonatal mortality and neonatal composite morbidity in EONS were 14.9% and 67.8%, respectively, and there was no difference in neonatal morbidity and mortality between neonates whose mothers showed fever as a sign of clinical chorioamnionitis and those whose mothers did not. Conclusion The renouncement of fever as a prerequisite for the criteria of clinical chorioamnionitis could increase sensitivity for the identification of EONS, a serious outcome of preterm birth. Tweetable abstract The renouncement of fever as an essential can increase sensitivity for prediction of neonatal sepsis.