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| Status |
Public on Feb 21, 2018 |
| Title |
Metallothionein I as a direct link between therapeutic hematopoietic stem/progenitor cells and cerebral protection in stroke |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Increasing evidence indicates stem cell transplantation may be an effective stroke treatment but little is known about the direct impact of transplanted cells on injured brain tissue. We investigated the effects of lineage negative murine hematopoietic stem/progenitor cells (HSPCs) on the cerebral microcirculation following ischemia-reperfusion injury (I/RI). Following subsequent evaluation of the mRNA transcriptome of the explanted HSPCs, we assessed whether metallothionein (MT)-1, (increased in explanted HSPCs from I/R mice) administration was able to evoke similar neuro-protection following cerebral I/RI.
Methods and Results: Murine HSPCs administered intravenously 24 hours (h) post cerebral I/R were selectively recruited to the brain of I/RI mice. Mice treated with HSPCs displayed decreased disease severity for up to 2-weeks post cerebral I/R, as evidenced by decreased mortality rate, decreased infarct volume, improved functional outcome, reduced microglial activation and elevated plasma levels of anti-inflammatory interleukin-10. Using confocal intravital microscopy, we found that transplanted cells had emigrated into the brain parenchyma and that RNA-seq analysis of explanted HSPCs indicated significantly increased levels of metallothionein transcripts, in particular MT-1. We further determined that treatment of mice with MT-1 significantly reduced neurological score and IV.
Conclusions: These studies provide further evidence for HSPCs as a promising therapeutic strategy in promoting repair following cerebral I/RI, potentially via a MT-1 mechanism.
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| Overall design |
Murine HSPCs were administered into mice with I/RI intravenously 24 hours post cerebral I/R and selectively recruited to the brain. RNA profiles of explanted HSPCs were determined by RNA sequencing.
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| Contributor(s) |
Smith HK, Omura S, Vital SA, Becker F, Tsunoda I, Gavins FN |
| Citation(s) |
29269399 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R56 HL125572 |
Cerebral Microvascular Dysfunction in Sickle Cell Disease |
LSU HEALTH SCIENCES CENTER - SHREVEPORT |
Felicity Nicola Emma Gavins |
| P30 GM110703 |
COBRE Center for Molecular and Tumor Virology |
LSU HEALTH SCIENCES CENTER - SHREVEPORT |
DENNIS John O'CALLAGHAN |
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| |
| Submission date |
Mar 09, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Seiichi Omura |
| E-mail(s) |
omura.s@hotmail.com
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| Organization name |
Kindai University Faculty of Medicine
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| Department |
Department of Microbiology
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| Street address |
377-2 Ohnohigashi
|
| City |
Osakasayama |
| State/province |
Osaka |
| ZIP/Postal code |
589-8511 |
| Country |
Japan |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA378600 |
| SRA |
SRP101617 |
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