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Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation-Induced Hematopoietic Injury.

Publication ,  Journal Article
Piryani, SO; Jiao, Y; Kam, AYF; Liu, Y; Vo-Dinh, T; Chen, BJ; Chao, NJ; Doan, PL
Published in: Int J Radiat Oncol Biol Phys
June 1, 2019

PURPOSE: Extracellular vesicles (EVs) are shed vesicles that bear a combination of nucleic acids and proteins. EVs are becoming recognized as a mode of cell-to-cell communication. Because hematopoietic stem cells reside in proximity to endothelial cells (ECs), we investigated whether EC-derived EVs could regulate hematopoietic stem cell regeneration after ionizing radiation. METHODS AND MATERIALS: We generated EVs derived from primary murine marrow ECs. We sought to determine the response of irradiated hematopoietic stem and progenitor cells to syngeneic or allogeneic EVs in culture assays. Starting 24 hours after either sublethal or lethal irradiation, mice were treated with EVs or saline or cultured primary marrow endothelial cells to determine the hematopoietic response in vivo. RESULTS: We demonstrate that EVs bear nuclear material and express EC-specific markers. Treatment with EVs promoted cell expansion and increased the number of colony-forming units compared to irradiated, hematopoietic cell cultures treated with cytokines alone. After total body irradiation, EV-treated mice displayed preserved marrow cellularity, marrow vessel integrity, and prolonged overall survival compared with controls treated with saline. Treatment of irradiated hematopoietic stem/progenitor cells (HSPCs) with EVs from different genetic strains showed results similar to treatment of HSPCs from syngeneic EVs. Mechanistically, treatment of irradiated HSPCs with EVs resulted in decreased levels of annexin V+ apoptotic cell death, which is mediated in part by tissue inhibitor of metalloproteinase-1. CONCLUSIONS: Our findings show that syngeneic or allogeneic EVs could serve as cell-derived therapy to deliver physiologic doses of nucleic acids and growth factors to hematopoietic cells to accelerate hematopoietic regeneration.

Duke Scholars

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Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

June 1, 2019

Volume

104

Issue

2

Start / End Page

291 / 301

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Tissue Inhibitor of Metalloproteinase-1
  • Regeneration
  • Radiation Injuries
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Mesenchymal Stem Cell Transplantation
  • Hematopoietic Stem Cells
 

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Piryani, S. O., Jiao, Y., Kam, A. Y. F., Liu, Y., Vo-Dinh, T., Chen, B. J., … Doan, P. L. (2019). Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation-Induced Hematopoietic Injury. Int J Radiat Oncol Biol Phys, 104(2), 291–301. https://doi.org/10.1016/j.ijrobp.2019.02.008
Piryani, Sadhna O., Yiqun Jiao, Angel Y. F. Kam, Yang Liu, Tuan Vo-Dinh, Benny J. Chen, Nelson J. Chao, and Phuong L. Doan. “Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation-Induced Hematopoietic Injury.Int J Radiat Oncol Biol Phys 104, no. 2 (June 1, 2019): 291–301. https://doi.org/10.1016/j.ijrobp.2019.02.008.
Piryani SO, Jiao Y, Kam AYF, Liu Y, Vo-Dinh T, Chen BJ, et al. Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation-Induced Hematopoietic Injury. Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):291–301.
Piryani, Sadhna O., et al. “Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation-Induced Hematopoietic Injury.Int J Radiat Oncol Biol Phys, vol. 104, no. 2, June 2019, pp. 291–301. Pubmed, doi:10.1016/j.ijrobp.2019.02.008.
Piryani SO, Jiao Y, Kam AYF, Liu Y, Vo-Dinh T, Chen BJ, Chao NJ, Doan PL. Endothelial Cell-Derived Extracellular Vesicles Mitigate Radiation-Induced Hematopoietic Injury. Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):291–301.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

June 1, 2019

Volume

104

Issue

2

Start / End Page

291 / 301

Location

United States

Related Subject Headings

  • Whole-Body Irradiation
  • Tissue Inhibitor of Metalloproteinase-1
  • Regeneration
  • Radiation Injuries
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Mesenchymal Stem Cell Transplantation
  • Hematopoietic Stem Cells