Functional equivalence of stem cell and stem cell-derived extracellular vesicle transplantation to repair the irradiated brain
| Autor: | Tiffany Lui, Munjal M. Acharya, Ning Ru, Sharon Tang, Maria C. Angulo, Janet E. Baulch, Charles L. Limoli, Yaxuan Liang, Audrey L. Park, Sarah M. Smith, Vahan Martirosian, Erich Giedzinski, Nicole N. Chmielewski, Celine Lu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Medical Biotechnology Hippocampal formation Regenerative Medicine neural stem cell 0302 clinical medicine Neural Stem Cells Medicine 2.1 Biological and endogenous factors cranial irradiation Cancer lcsh:R5-920 Microglia lcsh:Cytology General Medicine Extracellular vesicle Neural stem cell 3. Good health medicine.anatomical_structure Cranial irradiation Neurological Stem Cell Research - Nonembryonic - Non-Human Stem cell lcsh:Medicine (General) brain 1.1 Normal biological development and functioning Clinical Sciences Neuroprotection 03 medical and health sciences Extracellular Vesicles Rats Nude Rare Diseases Tissue Engineering and Regenerative Medicine Animals Humans lcsh:QH573-671 Transplantation 5.2 Cellular and gene therapies business.industry Neurosciences Cell Biology Stem Cell Research Rats Brain Disorders Brain Cancer 030104 developmental biology extracellular vesicle Biochemistry and Cell Biology business Neuroscience Postsynaptic density 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem cells translational medicine, vol 9, iss 1 Stem Cells Translational Medicine Stem Cells Translational Medicine, Vol 9, Iss 1, Pp 93-105 (2020) |
| Popis: | Cranial radiotherapy, although beneficial for the treatment of brain tumors, inevitably leads to normal tissue damage that can induce unintended neurocognitive complications that are progressive and debilitating. Ionizing radiation exposure has also been shown to compromise the structural integrity of mature neurons throughout the brain, an effect believed to be at least in part responsible for the deterioration of cognitive health. Past work has shown that cranially transplanted human neural stem cells (hNSCs) or their extracellular vesicles (EVs) afforded long‐term beneficial effects on many of these cognitive decrements. To provide additional insight into the potential neuroprotective mechanisms of cell‐based regenerative strategies, we have analyzed hippocampal neurons for changes in structural integrity and synaptic remodeling after unilateral and bilateral transplantation of hNSCs or EVs derived from those same cells. Interestingly, hNSCs and EVs similarly afforded protection to host neurons, ameliorating the impact of irradiation on dendritic complexity and spine density for neurons present in both the ipsilateral and contralateral hippocampi 1 month following irradiation and transplantation. These morphometric improvements were accompanied by increased levels of glial cell‐derived growth factor and significant attenuation of radiation‐induced increases in postsynaptic density protein 95 and activated microglia were found ipsi‐ and contra‐lateral to the transplantation sites of the irradiated hippocampus treated with hNSCs or hNSC‐derived EVs. These findings document potent far‐reaching neuroprotective effects mediated by grafted stem cells or EVs adjacent and distal to the site of transplantation and support their potential as therapeutic agents to counteract the adverse effects of cranial irradiation. Regenerative medicine holds promise for restoring brain structure and function following cancer relevant radiotherapy. These studies document potent distal neuroprotective effects mediated by bilateral and unilateral grafted stem cells or extracellular vesicles to the site of transplantation and support their potential as therapeutic agents to counteract the adverse effects of cranial irradiation. |
| Databáze: | OpenAIRE |
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