Stem cell-derived extracellular vesicles to reverse radiation-induced brain injury

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Grant Award Details

Grant Number:
DISC2-12400
Investigator(s):
Human Stem Cell Use:
Award Value:
$1,064,724
Status:
Closed

Progress Reports

Reporting Period:
Year 2 + NCE

Grant Application Details

Application Title:

Stem cell-derived extracellular vesicles to reverse radiation-induced brain injury

Public Abstract:
Research Objective

These preclinical studies will discover the efficacy of stem cell-derived, nanoscale, extracellular vesicles (candidate) to treat adverse effects of cancer therapy on brain function and cognition.

Impact

Stem cell-derived extracellular vesicles will address the confounders of stem cells (tumors, immunorejection, immunosuppression) & mitigate debilitating side-effects of cancer therapy on the brain.

Major Proposed Activities

  • Demonstrate the effectiveness of IV injections of stem cell-derived, nanoscale, extracellular-vesicles (EVs) to improve cognition in the mouse model of radiation- and chemo-therapy for brain cancers.
  • Determine the ability of EV treatment to protect against adverse effects of cancer therapy including neuro-inflammation, synaptic and micro-vascular damage in the brain.
  • Establish the neurocognitive benefits of injecting stem cell-derived-EV in brain cancer-bearing mice receiving combined radiation- and chemo-therapy (temozolomide, TMZ).
  • Elucidate the impact of stem cell-derived-EV injections on neuropathological hallmarks of radiation- and chemo-therapy (TMZ) in the cancer-bearing mice brains.
  • Determine the safety and rule out the toxicity of stem cell-derived EV treatment in brain and peripheral organs in the mice receiving radiation- and chemo-therapy (TMZ) for brain cancer.
  • Confirm miRNA-124-based mechanism (commonly found within the EV cargo) of stem cell-derived EV-mediated neuroprotection in the mice undergoing radiation- and chemo-therapy for brain cancers.
Statement of Benefit to California:
In California, nearly 187,000 patients diagnosed with cancer will be alive in 5 years & more than 1.88 million have a history of cancer. Importantly, adult & childhood cancer survivors suffer from severe & persistent cognitive deficits that adversely affect their quality of life (QOL). A stem cell-based therapeutic could reduce inflammation & restore the cognitive function that may significantly improve patient’s QOL, reduce financial hardship on patients, caregivers & the state of California.