Contributions of phase resetting and interlimb coordination to the adaptive control of hindlimb obstacle avoidance during locomotion in rats: a simulation study.

Obstacle avoidance during locomotion is essential for safe, smooth locomotion. Physiological studies regarding muscle synergy have shown that the combination of a small number of basic patterns produces the large part of muscle activities during locomotion and the addition of another pattern explains muscle activities for obstacle avoidance. Furthermore, central pattern generators in the spinal cord are thought to manage the timing to produce such basic patterns. In the present study, we investigated sensory-motor coordination for obstacle avoidance by the hindlimbs of the rat using a neuromusculoskeletal model. We constructed the musculoskeletal part of the model based on empirical anatomical data of the rat and the nervous system model based on the aforementioned physiological findings of central pattern generators and muscle synergy. To verify the dynamic simulation by the constructed model, we compared the simulation results with kinematic and electromyographic data measured during actual locomotion in rats. In addition, we incorporated sensory regulation models based on physiological evidence of phase resetting and interlimb coordination and examined their functional roles in stepping over an obstacle during locomotion. Our results show that the phase regulation based on interlimb coordination contributes to stepping over a higher obstacle and that based on phase resetting contributes to quick recovery after stepping over the obstacle. These results suggest the importance of sensory regulation in generating successful obstacle avoidance during locomotion

Induction of functional xeno-free MSCs from human iPSCs via a neural crest cell lineage

iPS細胞から間葉系幹細胞の誘導方法を確立 --動物由来成分を含まず再生医療への利用に期待. 京都大学プレスリリース. 2022-09-15.A new method for inducing mesenchymal stem cells from iPS cells without using animal-derived components. 京都大学プレスリリース. 2022-09-27.Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells. Here, we induced MSCs from human induced pluripotent stem cells (iPSCs) via a neural crest cell (NCC) lineage under xeno-free conditions and evaluated their in vivo functions. We modified a previous MSC induction method to work under xeno-free conditions. Bovine serum albumin-containing NCC induction medium and fetal bovine serum-containing MSC induction medium were replaced with xeno-free medium. Through our optimized method, iPSCs differentiated into MSCs with high efficiency. To evaluate their in vivo activities, we transplanted the xeno-free-induced MSCs (XF-iMSCs) into mouse models for bone and skeletal muscle regeneration and confirmed their regenerative potency. These XF-iMSCs mainly promoted the regeneration of surrounding host cells, suggesting that they secrete soluble factors into affected regions. We also found that the peroxidasin and IGF2 secreted by the XF-iMSCs partially contributed to myotube differentiation. These results suggest that XF-iMSCs are important for future applications in regenerative medicine

A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells

Nakagawa, M.et al. A novel efficient feeder-free culture system forthe derivation of human induced pluripotent stem cells.Sci. Rep.4, 3594; DOI:10.1038/srep03594 (2014)

Effect of migratory behaviors on human induced pluripotent stem cell colony formation on different extracellular matrix proteins

Introduction: Understanding how extracellular matrix (ECM) protein composition regulates the process of human induced pluripotent stem cell (hiPSC) colony formation may facilitate the design of optimal cell culture environments. In this study, we investigated the effect of migratory behaviors on hiPSC colony formation on various ECM-coated surfaces. Methods: To quantify how different ECM proteins affect migratory behavior during the colony formation process, single cells were seeded onto surfaces coated with varying concentrations of different ECM proteins. Cell behavior was monitored by time-lapse observation, and quantitative analysis of migration rates in relation to colony formation patterns was performed. Actin cytoskeleton, focal adhesions, and cell–cell interactions were detected by fluorescence microscopy. Results: Time-lapse observations revealed that different mechanisms of colony formation were dependent upon the migratory behavior of cells on different ECM surfaces. HiPSCs formed tight colonies on concentrated ECM substrates, while coating with dilute concentrations of ECM yielded more motile cells and colonies capable of splitting into single cells or small clusters. Enhanced migration caused a reduction of cell–cell contacts that enabled splitting or merging between cells and cell clusters, consequently reducing the efficiency of clonal colony formation. High cell-to-cell variability in migration responses to ECM surfaces elicited differential focal adhesion formation and E-cadherin expression within cells and colonies. This resulted in variability within focal adhesions and further loss of E-cadherin expression by hiPSCs. Conclusions: Migration is an important factor affecting hiPSC colony-forming patterns. Regulation of migratory behavior can be an effective way to improve the expansion of hiPSCs while improving the process of clonal colony formation. We believe that this investigation provides a valuable method for understanding cell phenotypes and heterogeneity during colony formation in culture. Keywords: Human induced pluripotent stem cells, Cell migration, Extracellular matrix, Clonal colony formation, Cytoskeletal formation, Cell–cell interactio

Altered heterochromatin organization after perinatal exposure to zidovudine.

International audienceBACKGROUND: Zidovudine (3'-azido-3'-deoxythymidine, AZT), administered to pregnant women alone or in combination with other antiretroviral drugs, greatly reduces the mother-to-child transmission of HIV-1. The potential genotoxicity of these molecules is underestimated and wide-ranging evaluation of its biological and clinical consequences is required. METHODS: We investigated the nuclear organization of constitutive heterochromatin, a major domain participating in epigenetic regulation, in uninfected infants born to HIV-1-infected mothers treated with zidovudine and/or other nucleoside reverse transcriptase inhibitors (NRTIs) during pregnancy. We studied the organization of chromosome 1 heterochromatin (1q12) in peripheral leukocytes of 25 HIV-1-uninfected children (newborn to 9 years old): children born to HIV-1-infected mothers exposed to zidovudine and/or other NRTIs (n=15), children born to HIV-1-infected mothers not exposed to any NRTIs (n=6) and children born to HIV-1-uninfected mothers (n=4). RESULTS: Results differed significantly between NRTI-exposed and -unexposed children. By contrast, there was no difference between NRTI-unexposed children born to HIV-1-infected mothers and children born to HIV-uninfected mothers. The anomaly persisted in lymphocytes cultured for 48 h. There was no evidence of abnormal DNA methylation, a major feature of constitutive heterochromatin and associated with the loss of its structure. In a complementary sample of children, analysis of chromosome 11 and 16 heterochromatin suggests that the defect affects most of the other heterochromatic sites of the human genome. The heterochromatin defect persists long after the end of the exposure and appears in leukocytes of both myeloid and lymphoid lineages, suggesting that haematopoietic stem cells are affected

Validity of the 30-Second Chair-Stand Test to Assess Exercise Tolerance and Clinical Outcomes in Patients with Esophageal Cancer: A Retrospective Study with Reference to 6-Minute Walk Test Results

This retrospective study aimed to investigate the validity of a 30-sec chair stand test (CS-30) as a simple test to assess exercise tolerance and clinical outcomes in 53 Japanese patients with esophageal cancer. There was a strong correlation between the results of CS-30 and the 6-min walk test (6MWT), the gold standard for assessing exercise tolerance (r=0.759). Furthermore, fewer patients whose CS-30 score was greater than 16 (the cutoff value defined based on 6MWT) experienced pneumonia in their postoperative course. These results suggest that exercise tolerance could be assessed using CS-30, and its cutoff value may be useful in predicting postoperative pneumonia risk

Equivalency of nuclear transfer-derived embryonic stem cells to those derived from fertilized mouse blastocysts.

Therapeutic cloning, whereby nuclear transfer (NT) is used to generate embryonic stem cells (ESCs) from blastocysts, has been demonstrated successfully in mice and cattle. However, if NT-ESCs have abnormalities, such as those associated with the offspring produced by reproductive cloning, their scientific and medical utilities might prove limited. To evaluate the characteristics of NT-ESCs, we established more than 150 NT-ESC lines from adult somatic cells of several mouse strains. Here, we show that these NT-ESCs were able to differentiate into all functional embryonic tissues in vivo. Moreover, they were identical to blastocyst-derived ESCs in terms of their expression of pluripotency markers in the presence of tissue-dependent differentially DNA methylated regions, in DNA microarray profiles, and in high-coverage gene expression profiling. Importantly, the NT procedure did not cause irreversible damage to the nuclei. These similarities of NT-ESCs and ESCs indicate that murine therapeutic cloning by somatic cell NT can provide a reliable model for preclinical stem cell research