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Human induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) are considered as a promising cell source for transplantation and have been used for organoid fabrication to recapitulate central nervous system (CNS) diseases in vitro. The establishment of three-dimensional (3D) in vitro model with hiPSC-NPCs and control of their differentiation is significantly critical for understanding biological processes and CNS disease and regeneration. Here we implemented 3D methacrylated hyaluronic acid (Me-HA) hydrogels with encapsulation of hiPSC-NPCs as in vitro culture models and further investigated the role of the hydrogel rigidity on the cell behavior of hiPSC-NPCs. We first encapsulated single dispersive hiPSC-NPCs within both soft and stiff Me-HA hydrogel and found that hiPSC-NPCs gradually self-assembled and aggregated to form 3D spheroids. Then, the hiPSC-NPCs were laden into Me-HA hydrogels in the form of spheroids to evaluate their spontaneous differentiation in response to hydrogel rigidity. The soft Me-HA hydrogel-encapsulated hiPSC-NPCs displayed robust neurite outgrowth and showed high levels of spontaneous neural differentiation. We further encapsulated Down Syndrome (DS) patient-specific hiPSC-derived NPCs (DS-NPCs) spheroids within our hydrogels. DS-NPCs remained excellent cell viability in both soft and stiff Me-HA hydrogels. Similarly, soft hydrogels promoted neural differentiation of DS-NPCs by significantly upregulating neural maturation markers. This study demonstrates that soft matrix promotes neural differentiation of hiPSC-NPCs and HA-based hydrogels with hiPSC-NPCs or DS-NPCs are effective 3D models for CNS disease study.
Human induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) are considered as a promising cell source for transplantation and have been used for organoid fabrication to recapitulate central nervous system (CNS) diseases in vitro. The establishment of three-dimensional (3D) in vitro model with hiPSC-NPCs and control of their differentiation is significantly critical for understanding biological processes and CNS disease and regeneration. Here we implemented 3D methacrylated hyaluronic acid (Me-HA) hydrogels with encapsulation of hiPSC-NPCs as in vitro culture models and further investigated the role of the hydrogel rigidity on the cell behavior of hiPSC-NPCs. We first encapsulated single dispersive hiPSC-NPCs within both soft and stiff Me-HA hydrogel and found that hiPSC-NPCs gradually self-assembled and aggregated to form 3D spheroids. Then, the hiPSC-NPCs were laden into Me-HA hydrogels in the form of spheroids to evaluate their spontaneous differentiation in response to hydrogel rigidity. The soft Me-HA hydrogel-encapsulated hiPSC-NPCs displayed robust neurite outgrowth and showed high levels of spontaneous neural differentiation. We further encapsulated Down Syndrome (DS) patient-specific hiPSC-derived NPCs (DS-NPCs) spheroids within our hydrogels. DS-NPCs remained excellent cell viability in both soft and stiff Me-HA hydrogels. Similarly, soft hydrogels promoted neural differentiation of DS-NPCs by significantly upregulating neural maturation markers. This study demonstrates that soft matrix promotes neural differentiation of hiPSC-NPCs and HA-based hydrogels with hiPSC-NPCs or DS-NPCs are effective 3D models for CNS disease study.
The corticospinal tract (CST) is one of the most well-studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available.However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we proposed a novel method, using manually-drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heatmaps from 37 subjects for both the aforementioned tracts, which could be utilized as reference for clinicians to explore neuropathology in both trauma and disease states.Graphical abstract 1
Relevance Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality worldwide. Despite advances in treatment based on understanding of the mechanisms of brain injury after TBI, there is a clear need for new therapeutic strategies. Remote ischemic postconditioning (RIPostC) can be considered as a non-pharmacological technique to reduce secondary brain damage and improve clinical outcomes in patients with TBI.Aim of study Raising awareness of emergency physicians, neurosurgeons, neurologists, neurophysiologists about the possible use of the concept of RIPostC in patients with TBI.Material and methods To achieve this goal, the Results of clinical and experimental studies of the use of RIPostC after TBI were analyzed. Literature search was carried out in electronic search systems PubMed (https://pubmed.ncbi.nlm.nih.gov), eLibrary (https://elibrary.ru) using the keywords: “traumatic brain injury”, “remote ischemic conditioning”. A systematic search and selection of publications was performed in January–February 2023. The results of the review included patients with an established diagnosis of traumatic brain injury, followed by the use of RIPostC and animals with experimental modeling of TBI in various ways, followed by RIPostC.Conclusion The totality of data suggests that the use of the concept of RIPostC as a non-invasive protective technique in the provision of emergency care for patients with TBI may contribute to limiting secondary brain damage. However, the underlying neuroprotective processes are quite complex and need further study. Establishing the relationship of humoral, neurogenic and inflammatory reactions in response to the use of RIPostC in TBI will contribute to understanding the mechanisms of emerging neuroprotection, help ease the course of the disease and improve the clinical outcome.
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