Grafted human iPSC-derived neural progenitor cells express integrins and extend long-distance axons within the developing corticospinal tract
| العنوان: | Grafted human iPSC-derived neural progenitor cells express integrins and extend long-distance axons within the developing corticospinal tract |
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| المؤلفون: | Melissa R. Andrews, Lindsey H. Forbes |
| المصدر: | Frontiers in Cellular Neuroscience, Vol 13 (2019) Frontiers in Cellular Neuroscience |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Nervous system, induced pluripotent stem cell, Neurite, Integrin, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, neural progenitor cell, Induced pluripotent stem cell, sensorimotor cortex, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, biology, α9 integrin, Neural stem cell, Cell biology, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Corticospinal tract, biology.protein, TBR1, 030217 neurology & neurosurgery, Neuroscience, transplantation |
| الوصف: | After spinal cord injury (SCI), regeneration of adult motor axons such as axonsin the corticospinal tract (CST) is severely limited. Alongside the inhibitory lesionenvironment, most neuronal subtypes in the mature central nervous system (CNS) are intrinsically unrepairable. With age, expression of growth-promoting proteins in neurons, such as integrins, declines. Integrin receptors allow communication between the extracellular matrix (ECM) and cell cytoskeleton and their expression in axons facilitates growth and guidance throughout the ECM. The a9b1 integrin heterodimer binds to tenascin-C (TN-C), an ECM glycoprotein expressed during development and after injury. In the mature CST however, expression of the a9 integrin subunit is downregulated, adding to the intrinsic inability of axons to regenerate. Our previous work has shown the a9 integrin subunit is not trafficked within axons of mature CST or rubrospinal tracts (RSTs). Thus, here we have utilized human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) to increase expression of a9 integrin within the developing rat CST. We demonstrate that human NPCs (hNPCs) express endogenous levels of both a9 and b1 integrin subunits as well as cortical neuronmarkers such as chicken ovalbumin upstream promoter transcription factor (COUP-TF) interacting protein 2 (Ctip2) and T-box brain 1 (Tbr1). In addition, lentivirus-mediated a9 integrin overexpression in hNPCs resulted in increased neurite outgrowth in the presence of TN-C in vitro. Following transplantation into the sensorimotor cortex of newborn rats, both wild type (WT) and a9-expressing hNPCs extend along the endogenous CST and retain expression of a9 throughout the length of the axonal compartment for up to 8 weeks following transplantation. These data highlight the growth potential of transplanted human iPSCs which may be a future target for regenerative therapies after nervous system injury. |
| وصف الملف: | text |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e54dbadc8667f06cca505f602433a58f https://eprints.soton.ac.uk/428286/ |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e54dbadc8667f06cca505f602433a58f |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |