A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury.

Animals Biomarkers / metabolism Brain Injuries / therapy Disease Models, Animal Rats Rats, Sprague-Dawley Regenerative Medicine / methods Stem Cell Transplantation / methods
MRI cerebral palsy hypoxic-ischemic injury neuroprotection patient stratification penumbra recovery-of-function regenerative medicine stroke transplantation

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
12 05 2020
Historique:
received: 02 08 2019
revised: 16 01 2020
accepted: 16 04 2020
entrez: 14 5 2020
pubmed: 14 5 2020
medline: 21 5 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2020.107622 PMID: 32402283
pubmed: 32402283
pii: S2211-1247(20)30575-1
doi: 10.1016/j.celrep.2020.107622
pii:
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

107622

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS059770
Pays : United States

Informations de copyright

Copyright © 2020. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Interests A.O. holds the following patents related to the HRS method: United States patent 8731261; European patent 11748009.5-1265. E.Y.S. holds the following patents related to the HFB2050 hNSCs: United States patents 5,958,767; 6,680,198B1; 6,541,255B1; Canadian patent 2,339,411; European patent 99942022.7.

Auteurs

Richard E Hartman (RE)

Department of Psychology, Loma Linda University, Loma Linda, CA 92350, USA.

Neal H Nathan (NH)

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.

Nirmalya Ghosh (N)

Department of Pediatrics, Loma Linda University, Loma Linda, CA 92350, USA.

Cameron D Pernia (CD)

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.

Janessa Law (J)

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; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92037, USA.

Ruslan Nuryyev (R)

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.

Amy Plaia (A)

Department of Pediatrics, Loma Linda University, Loma Linda, CA 92350, USA.

Alena Yusof (A)

Department of Pediatrics, Loma Linda University, Loma Linda, CA 92350, USA.

Beatriz Tone (B)

Department of Pediatrics, Loma Linda University, Loma Linda, CA 92350, USA.

Melissa Dulcich (M)

Department of Psychology, Loma Linda University, Loma Linda, CA 92350, USA.

Dustin R Wakeman (DR)

Center for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Nejmi Dilmac (N)

Center for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Walter D Niles (WD)

Center for Stem Cells & Regenerative Medicine, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Richard L Sidman (RL)

Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.

Andre Obenaus (A)

Department of Pediatrics, Loma Linda University, Loma Linda, CA 92350, USA; Department of Pathology & Human Anatomy, Loma Linda University, Loma Linda, CA 92350, USA; Department of Pediatrics, Center for the Neurobiology of Learning & Memory, Preclinical and Translational Imaging Center, University of California, Irvine, CA 92697, USA.

Evan Y Snyder (EY)

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; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: esnyder@sbp.edu.

Stephen Ashwal (S)

Department of Pediatrics, Loma Linda University, Loma Linda, CA 92350, USA. Electronic address: sashwal@llu.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Plaies et blessures › Traumatismes du système nerveux › Traumatismes cranioencéphaliques › Lésions encéphaliques › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Professions de santé › Médecine › Médecine régénérative › A Biomarker for Predicting Responsiveness to...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › A Biomarker for Predicting Responsiveness to...