Human Glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 G93A mouse model of ALS

Angelo C. Lepore, John O'Donnell, Andrew S. Kim, Timothy Williams, Alicia Tuteja, Mahendra S. Rao, Linda L. Kelley, James T. Campanelli, Nicholas J Maragakis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere25968
JournalPLoS One
Volume6
Issue number10
DOIs
StatePublished - Oct 5 2011

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Amyotrophic Lateral Sclerosis
neuroglia
spinal cord
Neuroglia
astrocytes
Astrocytes
Transplantation
animal models
therapeutics
Transplants
Motor Neurons
motor neurons
Neurons
Rodentia
rodents
Tissue
Survival
mice
Therapeutics
in vivo studies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Human Glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 G93A mouse model of ALS. / Lepore, Angelo C.; O'Donnell, John; Kim, Andrew S.; Williams, Timothy; Tuteja, Alicia; Rao, Mahendra S.; Kelley, Linda L.; Campanelli, James T.; Maragakis, Nicholas J.

In: PLoS One, Vol. 6, No. 10, e25968, 05.10.2011.

Research output: Contribution to journalArticle

Lepore, AC, O'Donnell, J, Kim, AS, Williams, T, Tuteja, A, Rao, MS, Kelley, LL, Campanelli, JT & Maragakis, NJ 2011, 'Human Glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 G93A mouse model of ALS', PLoS One, vol. 6, no. 10, e25968. https://doi.org/10.1371/journal.pone.0025968
Lepore, Angelo C. ; O'Donnell, John ; Kim, Andrew S. ; Williams, Timothy ; Tuteja, Alicia ; Rao, Mahendra S. ; Kelley, Linda L. ; Campanelli, James T. ; Maragakis, Nicholas J. / Human Glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 G93A mouse model of ALS. In: PLoS One. 2011 ; Vol. 6, No. 10.
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