Department of Psychology, Loma Linda University, Loma Linda, CA 92350, USA.
Center for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA.
Cell Rep. 2020 May 12;31(6):107622. doi: 10.1016/j.celrep.2020.107622.
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.
迄今为止，尚无基于与细胞治疗机制一致的临床或分子特征的针对特定接受者的干细胞疗法，也没有针对其他接受者的疗法。我们在临床前阶段通过一个典型的场景来解决这一挑战：针对围产期/新生儿脑缺氧缺血性损伤（HII）的人神经干细胞（hNSC）。我们证明了一种具有临床转化潜力的磁共振成像（MRI）算法——层次区域分割，可以提供一种严格、快速、前瞻性、非侵入性的“生物标志物”，用于识别具有对 hNSC 的神经保护作用机制反应的分子特征的病变。只有在存在可通过 MRI 测量的半影时，可阻止其发展为坏死核心，hNSC 才能改善病变、运动和/或认知结果；核心区域永远不会改善。与核心不同，半影的特征是与可挽救性相关的分子特征。因此，只有具有半影>核心体积的病变才应使用细胞进行治疗，因此此类测量可以说是再生医学选择的生物标志物。
