Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS.

Authors

Angelo C Lepore, Department of Neuroscience, Thomas Jefferson University Medical CollegeFollow
John O'Donnell, Department of Neurology, Johns Hopkins University School of MedicineFollow
Andrew S Kim, Department of Neurology, Johns Hopkins University School of MedicineFollow
Timothy Williams, Department of Neurology, Johns Hopkins University School of MedicineFollow
Alicia Tuteja, Department of Neurology, Johns Hopkins University School of MedicineFollow
Mahendra S Rao, Life Technologies, Carlsbad, California; Q Therapeutics, Salt Lake City, UtahFollow
Linda L Kelley, Department of Internal Medicine, University of Utah Health Sciences CenterFollow
James T Campanelli, Q Therapeutics, Salt Lake City, Utah; Department of Neurology, University of UtahFollow
Nicholas J Maragakis, Department of Neurology, Johns Hopkins University School of MedicineFollow

Document Type

Article

Publication Date

10-5-2011

Comments

This article has been peer reviewed and is published in PLoS One 2011, 6(10): e25968. The published version is available at DOI: 10.1371/journal.pone.0025968. © Public Library of Science

Abstract

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1(G93A) rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1(G93A) rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1(G93A) mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1(G93A) mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation.

Recommended Citation

Lepore, Angelo C; O'Donnell, John; Kim, Andrew S; Williams, Timothy; Tuteja, Alicia; Rao, Mahendra S; Kelley, Linda L; Campanelli, James T; and Maragakis, Nicholas J, "Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS." (2011). Department of Neuroscience Faculty Papers. Paper 2.
https://jdc.jefferson.edu/department_neuroscience/2