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Mechanochromism is a phenomenon in which mechanical stimuli change the optical properties of a material, such as its color and emission properties. Various materials exhibiting this behavior have been intensively studied. Mechanochromic materials that exploit liquid crystals have been previously reported. Using liquid crystals, properties different from those of conventional materials, such as anisotropic response and multicolored luminescence due to intermediate aggregation phase stabilization, can be expected. Recently, we reported the preparation and evaluation of the optical properties of liquid-crystalline mechanochromic dyes with cholesterol terminals. The dyes formed gels in some solvents, changed their emission color, and exhibited a friable response without reaching a crystalline state. In addition, film-forming properties, processability, and responsiveness were improved in thin films mixed with polymers. However, the mechanical and thermal stabilities of the gels were low. In this study, a compound similar to the polymerizable unit was synthesized to produce tougher gels. In addition, triblock polymers with a mechanoresponsive dye in the hard segment were synthesized. The xerogel film prepared from the monomer showed an irreversible blue shift in photoluminescent color by mechanical grinding and also exhibited linearly polarized photoluminescence by uniaxial grinding due to force-induced alignment. On the other hand, the xerogel film prepared from the triblock copolymer showed a blue shift in photoluminescent color that can approximately revert to the initial state by thermal annealing, though it showed no anisotropy by uniaxial grinding, indicating that polymerization partially preserves mechanical responsiveness.

Tumorigenesis is an important problem that needs to be addressed in the field of human stem/progenitor cell transplantation for the treatment of subacute spinal cord injury (SCI). When certain “tumorigenic” cell lines are transplanted into the spinal cord of SCI mice model, there is initial improvement of motor function, followed by abrupt deterioration secondary to the effect of tumor growth. A significant proportion of the transplanted cells remains undifferentiated after transplantation and is thought to increase the risk of tumorigenesis. In this study, using lentiviral vectors, we introduced the herpes simplex virus type 1 thymidine kinase (HSVtk) gene into a human induced pluripotent stem cell‐derived neural stem/progenitor cell (hiPSC‐NS/PC) line that is known to undergo tumorigenic transformation. Such approach enables selective ablation of the immature proliferating cells and thereby prevents subsequent tumor formation. In vitro, the HSVtk system successfully ablated the immature proliferative neural cells while preserving mature postmitotic neuronal cells. Similar results were observed in vivo following transplantation into the injured spinal cords of immune‐deficient (nonobese diabetic–severe combined immune‐deficient) mice. Ablation of the proliferating cells exerted a protective effect on the motor function which was regained after transplantation, simultaneously defending the spinal cord from the harmful tumor growth. These results suggest a potentially promising role of suicide genes in opposing tumorigenesis during stem cell therapy. This system allows both preventing and treating tumorigenesis following hiPSC‐NS/PC transplantation without sacrificing the improved motor function. Stem Cells Translational Medicine 2019;8:260&270 The herpes simplex virus thymidine kinase (HSVtk) gene was introduced into a tumorigenic cell line of human induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) prior to transplantation into spinal cord injury mouse models. Administration of ganciclovir (GCV) following transplantation successfully ablated the immature tumorigenic cells while preserving the mature neuronal cells and the improved motor function.

Resolving the immunogenicity of cells derived from induced pluripotent stem cells (iPSCs) remains an important challenge for cell transplant strategies that use banked allogeneic cells. Thus, we evaluated the immunogenicity of mouse fetal neural stem/progenitor cells (fetus-NSPCs) and iPSC-derived neural stem/progenitor cells (iPSC-NSPCs) both in vitro and in vivo . Flow cytometry revealed the low expression of immunological surface antigens, and these cells survived in all mice when transplanted syngeneically into subcutaneous tissue and the spinal cord. In contrast, an allogeneic transplantation into subcutaneous tissue was rejected in all mice, and allogeneic cells transplanted into intact and injured spinal cords survived for 3 months in approximately 20% of mice. In addition, cell survival was increased after co-treatment with an immunosuppressive agent. Thus, the immunogenicity and post-transplantation immunological dynamics of iPSC-NSPCs resemble those of fetus-NSPCs.

Transplantation of human‐induced pluripotent stem cell‐derived neural stem/progenitor cells (hiPSC‐NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC‐NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long‐term observation of hiPSC‐NS/PCs post‐transplantation suggested some “unsafe” differentiation‐resistant properties, resulting in disordered overgrowth. These findings suggest that, even if “safe” NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular‐functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)‐positive undifferentiated neural cells in the CNS of immune‐deficient (nonobese diabetic‐severe combined immune‐deficient) mice after hiPSC‐NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC‐NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC‐NS/PCs‐derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC‐NS/PCs‐derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine. By utilizing the characteristic of neural stem/progenitor cells (NS/PCs) to express translocator protein (TSPO), positron emission tomography (PET) with TSPO ligand was able to visualize residual immature neural cells after NS/PCs transplantation.

Study designRetrospective multicenter study.ObjectivesAlthough surgery is frequently selected for the treatment of idiopathic spinal cord herniation (ISCH), its impact on functional outcomes has yet to be fully understood given the limited number of patients in previous studies. This study aims to evaluate the symptomatic history and surgical outcomes of ISCH.SettingThree institutions in Japan.MethodsA total of 34 subjects with ISCH were retrospectively enrolled and followed up for at least 2 years. Demographic information, imaging findings, and clinical outcomes were collected. Functional status was assessed using the JOA score.ResultsThe types of neurologic deficit were monoparesis, Brown–Sequard, and paraparesis in 5, 17, and 12 cases, with their mean disease duration being 1.2, 4.2, and 5.8 years, respectively. Significant differences in disease duration were observed between the monoparesis and Brown–Sequard groups (p < 0.01) and between the monoparesis and paraparesis groups (p = 0.04). Surgery promoted significantly better recovery rates from baseline. Correlations were observed between age at surgery and recovery rate (p < 0.01) and between disease duration and recovery rate (p = 0.04). The mean recovery rates were 82.6%, 51.6%, and 29.1% in the monoparesis, Brown–Sequard, and paraparesis groups, respectively. The monoparesis group had a significantly higher recovery rate than did the Brown–Sequard (p = 0.045) and paraparesis groups (p < 0.01).ConclusionsLonger disease duration was correlated with the progression of neurologic deficit. Older age, and worse preoperative neurologic status hindered postoperative functional recovery. These results highlight the need to consider surgical timing before neurologic symptoms deteriorate.

Abstract Single-cell RNA sequencing has enabled researchers to quantify the transcriptomes of individual cells, infer cell types and investigate differential expression among cell types, which will lead to a better understanding of the regulatory mechanisms of cell states. Transcript diversity caused by phenomena such as aberrant splicing events have been revealed, and differential expression of previously unannotated transcripts might be overlooked by annotation-based analyses. Accordingly, we have developed an approach to discover overlooked differentially expressed (DE) gene regions that complements annotation-based methods. Our algorithm decomposes mapped count data matrix for a gene region using non-negative matrix factorization, quantifies the differential expression level based on the decomposed matrix, and compares the differential expression level based on annotation-based approach to discover previously unannotated DE transcripts. We performed single-cell RNA sequencing for human neural stem cells and applied our algorithm to the dataset. We also applied our algorithm to two public single-cell RNA sequencing datasets correspond to mouse ES and primitive endoderm cells, and human preimplantation embryos. As a result, we discovered several intriguing DE transcripts, including a transcript related to the modulation of neural stem/progenitor cell differentiation.

Single-cell RNA sequencing has enabled researchers to quantify the transcriptomes of individual cells, infer cell types, and investigate differential expression among cell types, which will lead to a better understanding of the regulatory mechanisms of cell states. Transcript diversity caused by phenomena such as aberrant splicing events have been revealed, and differential expression of previously unannotated transcripts might be overlooked by annotation-based analyses. Accordingly, we have developed an approach to discover overlooked differentially expressed (DE) gene regions that complements annotation-based methods. We applied our algorithm to two datasets and discovered several intriguing DE transcripts, including a transcript related to the modulation of neural stem/progenitor cell differentiation.

The circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology. The circadian clock is an internal mechanism that controls various physiological processes, such as the sleep-wake cycle, but its precise regulation is challenging. Here, the authors develop a visible light-responsive inhibitor of casein kinase I which controls the period and phase of cellular and tissue circadian rhythms in a reversible manner.