| RRC ID |
88271
|
| Author |
Rocca CJ, Goodman SM, Dulin JN, Haquang JH, Gertsman I, Blondelle J, Smith JLM, Heyser CJ, Cherqui S.
|
| Title |
Transplantation of wild-type mouse hematopoietic stem and progenitor cells ameliorates deficits in a mouse model of Friedreich's ataxia.
|
| Journal |
Sci Transl Med
|
| Abstract |
Friedreich's ataxia (FRDA) is an incurable autosomal recessive neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin due to an intronic GAA-repeat expansion in the FXN gene. We report the therapeutic efficacy of transplanting wild-type mouse hematopoietic stem and progenitor cells (HSPCs) into the YG8R mouse model of FRDA. In the HSPC-transplanted YG8R mice, development of muscle weakness and locomotor deficits was abrogated as was degeneration of large sensory neurons in the dorsal root ganglia (DRGs) and mitochondrial capacity was improved in brain, skeletal muscle, and heart. Transplanted HSPCs engrafted and then differentiated into microglia in the brain and spinal cord and into macrophages in the DRGs, heart, and muscle of YG8R FRDA mice. We observed the transfer of wild-type frataxin and Cox8 mitochondrial proteins from HSPC-derived microglia/macrophages to FRDA mouse neurons and muscle myocytes in vivo. Our results show the HSPC-mediated phenotypic rescue of FRDA in YG8R mice and suggest that this approach should be investigated further as a strategy for treating FRDA.
|
| Volume |
9(413)
|
| Published |
2017-10-25
|
| DOI |
10.1126/scitranslmed.aaj2347
|
| PII |
9/413/eaaj2347
|
| PMID |
29070698
|
| PMC |
PMC5735830
|
| MeSH |
Animals
Behavior, Animal
Cell Differentiation
Disease Models, Animal
Fibroblasts / metabolism
Frataxin
Friedreich Ataxia / pathology
Friedreich Ataxia / physiopathology
Friedreich Ataxia / therapy*
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells / cytology*
Hematopoietic Stem Cells / metabolism
Iron-Binding Proteins / metabolism
Locomotion
Macrophages / metabolism
Mice, Inbred C57BL
Mice, Transgenic
Microglia / metabolism
Mitochondria / metabolism
Mitochondrial Proteins / metabolism
Nervous System / pathology
Phagocytosis
Sensory Receptor Cells / pathology
|
| IF |
16.304
|
| Resource |
| Mice |
RBRC02250 |
