A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury
| Autor: | Dustin R. Wakeman, Nirmalya Ghosh, Amy Plaia, Nejmi Dilmac, Walter D. Niles, Richard E. Hartman, Ruslan Nuryyev, Evan Y. Snyder, Neal H. Nathan, Melissa S. Dulcich, Alena Yusof, Richard L. Sidman, Beatriz Tone, Stephen Ashwal, Janessa B Law, Cameron D. Pernia, Andre Obenaus |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Regenerative Medicine Regenerative medicine Neuroprotection General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Animals Medicine medicine.diagnostic_test business.industry Penumbra Magnetic resonance imaging Stem-cell therapy Neural stem cell Rats Biomarker (cell) Transplantation Disease Models Animal 030104 developmental biology Brain Injuries business Neuroscience Biomarkers 030217 neurology & neurosurgery Stem Cell Transplantation |
| Zdroj: | Cell Reports. 31:107622 |
| ISSN: | 2211-1247 |
| Popis: | To date, no stem cell therapy has been directed to specific recipients-and, conversely, withheld from others-based on a clinical or molecular profile congruent with that cell's therapeutic mechanism-of-action (MOA) for that condition. We address this challenge preclinically with a prototypical scenario: human neural stem cells (hNSCs) against perinatal/neonatal cerebral hypoxic-ischemic injury (HII). We demonstrate that a clinically translatable magnetic resonance imaging (MRI) algorithm, hierarchical region splitting, provides a rigorous, expeditious, prospective, noninvasive "biomarker" for identifying subjects with lesions bearing a molecular profile indicative of responsiveness to hNSCs' neuroprotective MOA. Implanted hNSCs improve lesional, motor, and/or cognitive outcomes only when there is an MRI-measurable penumbra that can be forestalled from evolving into necrotic core; the core never improves. Unlike the core, a penumbra is characterized by a molecular profile associated with salvageability. Hence, only lesions characterized by penumbral > core volumes should be treated with cells, making such measurements arguably a regenerative medicine selection biomarker. |
| Databáze: | OpenAIRE |
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