Silicate Microfiber Scaffolds Support the Formation and Expansion of the Cortical Neuronal Layer of Cerebral Organoids With a Sheet-Like Configuration

Terada Eisaku, Bamba Yohei, Takagaki Masatoshi, et al. Silicate Microfiber Scaffolds Support the Formation and Expansion of the Cortical Neuronal Layer of Cerebral Organoids With a Sheet-Like Configuration. Stem Cells Translational Medicine 9, 519 (2023); https://doi.org/10.1093/stcltm/szad066.Cerebral organoids (COs) are derived from human-induced pluripotent stem cells in vitro and mimic the features of the human fetal brain. The development of COs is largely dependent on “self-organization” mechanisms, in which differentiating cells committed to cortical cells autonomously organize into the cerebral cortex-like tissue. However, extrinsic manipulation of their morphology, including size and thickness, remains challenging. In this study, we discovered that silicate microfiber scaffolds could support the formation of cortical neuronal layers and successfully generated cortical neuronal layers, which are 9 times thicker than conventional COs, in 70 days. These cortical neurons in the silicate microfiber layer were differentiated in a fetal brain-like lamination pattern. While these cellular characteristics such as cortical neurons and neural stem/progenitor cells were like those of conventional COs, the cortical neuronal layers were greatly thickened in sheet-like configuration. Moreover, the cortical neurons in the scaffolds showed spontaneous electrical activity. We concluded that silicate microfiber scaffolds support the formation of the cortical neuronal layers of COs without disturbing self-organization-driven corticogenesis. The extrinsic manipulation of the formation of the cortical neuronal layers of COs may be useful for the research of developmental mechanisms or pathogenesis of the human cerebral cortex, particularly for the development of regenerative therapy and bioengineering

Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta

Study DesignWe established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods.PurposeWe aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use.Overview of LiteratureSBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues.MethodsFibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology.ResultsWe successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology.ConclusionsWe successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa

Bridging the great divide? Making sense of the human rights-CSR relationship in UK multinational companies

Human rights (HR) and corporate social responsibility (CSR) are both fields of knowledge and research that have been shaped by, and examine, the role of multi-national enterprises in society. Whilst scholars have highlighted the overlapping nature of CSR and HR, our understanding of this relationship within business practice remains vague and under-researched. To explore the interface between CSR and HR, this paper presents empirical data from a qualitative study involving 22 international businesses based in the UK. Through an analysis based on sensemaking, the paper examines how and where CSR and HR overlap, contrast and shape one another, and the role that companies’ international operations has on this relationship. The findings reveal a complex and multi-layered relationship between the two, and concludes that in contrast to management theory, companies have bridged the ‘great divide’ in varying degrees most notably in their implementation strategies

A rare case of lumbar disc herniation mimicking lumbar discal cyst after percutaneous endoscopic lumbar discectomy

We describe a 15-year-old girl who developed lumbar disc herniation (LDH) that mimicked discal cyst on magnetic resonance imaging (MRI) after percutaneous endoscopic lumbar discectomy (PELD). She firstly underwent PELD at another hospital for right leg pain caused by L5-S1 level LDH. Her leg pain temporarily relieved, however, the leg pain recurred soon after the surgery. Postoperative T2-weighted MRI showed that the right S1 nerve root was compressed by a round lesion that had an iso-intense wall and highly intense watery content. At that point, postoperative discal cyst was diagnosed, and she underwent PELD again 3 months after the initial surgery. However, the pain persisted after the second surgery, and she came to our hospital. MRI showed that the lesion had remained the same size as compared to the last surgery. Since two times endoscopic surgery was failed, we performed microscopic posterior decompression and found that the lesion actually contained not a cyst but a wet nucleus pulposus, which was different from what we had expected to find. The pain was alleviated immediately after the surgery. As signal intensity on MRI differs depending on the amount of moisture in the LDH, it should be noted that the LDH sometimes looks like a discal cyst on MRI

Continuous Monitoring of Changes in Heart Rate during the Periprocedural Course of Carotid Artery Stenting Using a Wearable Device: A Prospective Observational Study

This prospective observational study will evaluate the change in heart rate (HR) during the periprocedural course of carotid artery stenting (CAS) via continuous monitoring using a wearable device. The participants were recruited from our outpatient clinic between April 2020 and March 2023. They were instructed to continuously wear the device from the last outpatient visit before admission to the first outpatient visit after discharge. The changes in HR of interest throughout the periprocedural course of CAS were assessed. In addition, the Bland-Altman analysis was adopted to compare the HR measurement made by the wearable device during CAS with that made by the electrocardiogram (ECG). A total of 12 patients who underwent CAS were included in the final analysis. The time-series analysis revealed that a percentage change in HR decrease occurred on day 1 following CAS and that the most significant HR decrease rate was 12.1% on day 4 following CAS. In comparing the measurements made by the wearable device and ECG, the Bland-Altman analysis revealed the accuracy of the wearable device with a bias of −1.12 beats per minute (bpm) and a precision of 3.16 bpm. Continuous HR monitoring using the wearable device indicated that the decrease in HR following CAS could persist much longer than previously reported, providing us with unique insights into the physiology of carotid sinus baroreceptors

Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes

In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations

Abstract Background Lissencephaly, or smooth brain, is a severe congenital brain malformation that is thought to be associated with impaired neuronal migration during corticogenesis. However, the exact etiology of lissencephaly in humans remains unknown. Research on congenital diseases is limited by the shortage of clinically derived resources, especially for rare pediatric diseases. The research on lissencephaly is further limited because gyration in humans is more evolved than that in model animals such as mice. To overcome these limitations, we generated induced pluripotent stem cells (iPSCs) from the umbilical cord and peripheral blood of two lissencephaly patients with different clinical severities carrying alpha tubulin (TUBA1A) missense mutations (Patient A, p.N329S; Patient B, p.R264C). Results Neural progenitor cells were generated from these iPSCs (iPSC-NPCs) using SMAD signaling inhibitors. These iPSC-NPCs expressed TUBA1A at much higher levels than undifferentiated iPSCs and, like fetal NPCs, readily differentiated into neurons. Using these lissencephaly iPSC-NPCs, we showed that the neurons derived from the iPSCs obtained from Patient A but not those obtained from Patient B showed abnormal neurite extension, which correlated with the pathological severity in the brains of the patients. Conclusion We established iPSCs derived from lissencephaly patients and successfully modeled one aspect of the pathogenesis of lissencephaly in vitro using iPSC-NPCs and iPSC-derived neurons. The iPSCs from patients with brain malformation diseases helped us understand the mechanism underlying rare diseases and human corticogenesis without the use of postmortem brains

Additional file 9: Figure S3. of In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations

Differentiating pPBCAG-TUBA1A-IRES-AcGFP-transfected human NPCs. Measurements of AcGFP-positive neurites from each cell (μm: mean ± SEM, n = 50, one-way ANOVA followed by Dunnett’s test, **p < 0.01). Overexpression of mutant TUBA1A (p.N329S) interfered with neurite extension in the human NSCs (scale bar = 200 μm). (TIF 19759 kb