Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-Term Survival After Total Body Irradiation Without Additional Hematopoietic Stem Cell Support

TY - JOUR

T1 - Mesenchymal Stromal Cell-Derived Extracellular Vesicles Provide Long-Term Survival After Total Body Irradiation Without Additional Hematopoietic Stem Cell Support

AU - Schoefinius, Jill-Sandra

AU - Brunswig-Spickenheier, Bärbel

AU - Speiseder, Thomas

AU - Krebs, Sabrina

AU - Just, Ursula

AU - Lange, Claudia

N1 - © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

PY - 2017/12

Y1 - 2017/12

N2 - The therapeutic effect of mesenchymal stromal cells (MSC) in tissue regeneration is based mainly on the secretion of bioactive molecules. Here, we report that the radioprotective effect of mouse bone marrow derived mesenchymal stromal cells (mMSC) can be attributed to extracellular vesicles (EV) released from mMSC. The transplantation of mMSC-derived EV into lethally irradiated mice resulted in long-term survival but no improvement in short-term reconstitution of the recipients. Importantly, the radiation rescue was efficient without additional hematopoietic support. In vitro we show a protection by EV of irradiated hematopoietic stem cells but not progenitor cells using stroma-cell cultures and colony-forming assays. After systemic infusion into lethally irradiated recipients, labeled EV traveled freely through the body reaching the bone marrow within 2 hours. We further show that long-term repopulating Sca-1 positive and c-kit low-positive stem cells were directly targeted by EV leading to long-term survival. Collectively, our data suggest EV as an effective first-line treatment to combat radiation-induced hematopoietic failure which might also be helpful in alleviating myelosuppression due to chemotherapy and toxic drug reaction. We suggest the infusion of MSC-derived EV as efficient and immediate treatment option after irradiation injuries. Stem Cells 2017.

AB - The therapeutic effect of mesenchymal stromal cells (MSC) in tissue regeneration is based mainly on the secretion of bioactive molecules. Here, we report that the radioprotective effect of mouse bone marrow derived mesenchymal stromal cells (mMSC) can be attributed to extracellular vesicles (EV) released from mMSC. The transplantation of mMSC-derived EV into lethally irradiated mice resulted in long-term survival but no improvement in short-term reconstitution of the recipients. Importantly, the radiation rescue was efficient without additional hematopoietic support. In vitro we show a protection by EV of irradiated hematopoietic stem cells but not progenitor cells using stroma-cell cultures and colony-forming assays. After systemic infusion into lethally irradiated recipients, labeled EV traveled freely through the body reaching the bone marrow within 2 hours. We further show that long-term repopulating Sca-1 positive and c-kit low-positive stem cells were directly targeted by EV leading to long-term survival. Collectively, our data suggest EV as an effective first-line treatment to combat radiation-induced hematopoietic failure which might also be helpful in alleviating myelosuppression due to chemotherapy and toxic drug reaction. We suggest the infusion of MSC-derived EV as efficient and immediate treatment option after irradiation injuries. Stem Cells 2017.

KW - Journal Article

U2 - 10.1002/stem.2716

DO - 10.1002/stem.2716

M3 - SCORING: Journal article

C2 - 29024236

VL - 35

SP - 2379

EP - 2389

JO - STEM CELLS

JF - STEM CELLS

SN - 1066-5099

IS - 12

ER -