miRNA-based therapeutic potential of stem cell-derived extracellular vesicles: a safe cell-free treatment to ameliorate radiation-induced brain injury

Abstract

Purpose: This review compiles what is known about extracellular vesicles (EVs), their bioactive cargo, and how they might be used to treat radiation-induced brain injury. Radiotherapy (RT) is effective in cancer treatment, but can cause substantial damage to normal central nervous system tissue. Stem cell therapy has been shown to be effective in treating cognitive dysfunction arising from RT, but there remain safety concerns when grafting foreign stem cells into the brain (i.e. immunogenicity, teratoma). These limitations prompted the search for cell-free alternatives, and pointed to EVs that have been shown to have similar ameliorating effects in other tissues and injury models.

Conclusions: EVs are nano-scale and lipid-bound vesicles that readily pass the blood–brain barrier. Arguably the most important bioactive cargo within EVs are RNAs, in particular microRNAs (miRNA). A single miRNA can modulate entire gene networks and signalling within the recipient cell. Determining functionally relevant miRNA could lead to therapeutic treatments where synthetically-derived EVs are used as delivery vectors for miRNA. Stem cell-derived EVs can be effective in treating brain injury including radiation-induced cognitive deficits. Of particular interest are systemic modes of administration which obviate the need for invasive procedures.

Keywords:

• Extracellular vesicles
• stem cells
• cognitive function
• miRNA
• radiotherapy

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the Defense Threat Reduction Agency (HDTRA-1-16-1-022), California Institute for Regenerative Medicine (DISC1-10079) and UCI Research Seed Funding Program to JEB as well as the NINDS (5R01 NS074388) and the Defense Threat Reduction Agency (HDTRA 1-13-1-0022) to CLL.

Notes on contributors

Ron J. Leavitt

Ron J. Leavitt is a Ph.D. Candidate in the Department of Environmental Health Sciences in the School of Medicine at UC Irvine working in the Limoli Lab. His research involves mitigation of radiotherapy-induced cognitive deficit using a cell-free stem cell-based treatment and determining the mechanisms involved in rescue.

Charles L. Limoli

Dr. Charles L. Limoli is a radiation biologist in the Department of Radiation Oncology at UC Irvine. His studies of the CNS explore the mechanisms underlying cognitive impairments from cancer therapies and from and space radiation exposure.

Janet E. Baulch

Janet E. Baulch, Ph.D. is a Project Scientist in the Department of Radiation Oncology at UC Irvine. Her work evaluates the role of tissue-specific genomic and epigenetic changes in the radiation response. Her recent studies suggest that stem cell-derived EVs can mitigate the effects of irradiation on the brain.