You are hereDecember 11, 2017 | Mesenchymal Stem Cells
Extracellular Vesicles: A New Means to Rescue HSCs from the Effects of Irradiation
Review of “Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-Term Survival after Total Body Irradiation without Additional Hematopoietic Stem Cell Support” from STEM CELLS by Stuart P. Atkinson
Previous studies from the laboratory of Claudia Lange (University Medical Center Hamburg-Eppendorf, Germany) established that the transplantation of bone marrow (BM)-derived mesenchymal stromal cells (MSCs) provided long-term survival in a mouse model of total body irradiation (TBI) . Interestingly, MSCs preferentially accumulated in the lungs, suggesting that paracrine acting factors induced the observed long-term recovery of BM-derived peripheral blood cells without the need for hematopoietic stem cell (HSC) transplantation.
In a new STEM CELLS study, Schoefinius et al. now demonstrate that the secretion of extracellular vesicles from MSCs (MSC-EVs) protects and supports HSC recovery in vitro and long-term survival of recipients in vivo by specifically rescuing HSCs from the effects of irradiation .
Initial assessments in lethally irradiated mice discovered that both MSC and MSC-EV treatments permitted long-term survival, although MSC-EVs did not improve short-term survival. At 7 months, MSC- and MSC-EV-treated mice displayed a normal distribution of peripheral cell populations, with a slight acceleration in platelet recovery noted for MSC-EVs.
A combination of in vitro stroma-cell cultures and colony-forming assays and in vivo assays employing fluorescently EV labeling prior systemic injection established that EVs quickly and easily targeted long-term repopulating Sca-1 positive and c-kit low HSCs to rescue their function. However, MSC-EVs did not appear to target hematopoietic progenitors in the same manner.
Overall, this exciting new study suggests that EVs may represent an effective stem cell-free means to protect HSCs and reconstitute the hematopoietic system following radiation-induced hematopoietic failure or even myelosuppression following chemotherapy. The authors highlight the potential use of this system as part of an immediate response strategy given the relative ease of storage and handling , although they also note the need to fully appreciate how EVs rescue HSC function.
To keep abreast of all the new and exciting related studies, stay tuned to the Stem Cells Portal.
- Lange, C., et al., Radiation rescue: mesenchymal stromal cells protect from lethal irradiation. PLoS One 2011;6:e14486.
- Schoefinius, J.-S., et al., Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-Term Survival After Total Body Irradiation Without Additional Hematopoietic Stem Cell Support. STEM CELLS 2017;35:2379-2389.
- Sokolova, V., et al., Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids and Surfaces B: Biointerfaces 2011;87:146-150.