| Title |
Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS
|
|---|---|
| Published in |
PLOS ONE, October 2011
|
| DOI | 10.1371/journal.pone.0025968 |
| Pubmed ID | |
| Authors |
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 |
| 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. |
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|---|---|---|
| Chile | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
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|---|---|---|
| Australia | 2 | 2% |
| Brazil | 1 | 1% |
| Canada | 1 | 1% |
| Japan | 1 | 1% |
| United States | 1 | 1% |
| Unknown | 87 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 27 | 29% |
| Researcher | 14 | 15% |
| Student > Bachelor | 13 | 14% |
| Student > Master | 12 | 13% |
| Student > Doctoral Student | 5 | 5% |
| Other | 12 | 13% |
| Unknown | 10 | 11% |
| Readers by discipline | Count | As % |
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| Agricultural and Biological Sciences | 30 | 32% |
| Medicine and Dentistry | 26 | 28% |
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| Biochemistry, Genetics and Molecular Biology | 5 | 5% |
| Nursing and Health Professions | 1 | 1% |
| Other | 4 | 4% |
| Unknown | 14 | 15% |