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Normal tissue injury from accidental or therapeutic exposure to high-dose radiation can cause severe acute and delayed toxicities, which result in mortality and chronic morbidity. Exposure to single high-dose radiation leads to a multi-organ failure, known as acute radiation syndrome, which is caused by radiation-induced oxidative stress and DNA damage to tissue stem cells. The radiation exposure results in acute cell loss, cell cycle arrest, senescence, and early damage to bone marrow and intestine with high mortality from sepsis. There is an urgent need for developing medical countermeasures against radiation injury for normal tissue toxicity. In this review, we discuss the potential of applying secretory extracellular vesicles derived from mesenchymal stromal/stem cells, endothelial cells, and macrophages for promoting repair and regeneration of organs after radiation injury.

The immune system’s ability to recognize peptides on major histocompatibility molecules contributes to the eradication of cancers and pathogens. Tracking these responses in vivo could help evaluate the efficacy of immune interventions and improve mechanistic understanding of immune responses. For this purpose, we employ synTacs, which are dimeric major histocompatibility molecule scaffolds of defined composition. SynTacs, when labeled with positron-emitting isotopes, can noninvasively image antigen-specific CD8 + T cells in vivo. Using radiolabeled synTacs loaded with the appropriate peptides, we imaged human papillomavirus-specific CD8 + T cells by positron emission tomography in mice bearing human papillomavirus-positive tumors, as well as influenza A virus–specific CD8 + T cells in the lungs of influenza A virus–infected mice. It is thus possible to visualize antigen-specific CD8 + T-cell populations in vivo, which may serve prognostic and diagnostic roles. Antigen-specific CD8 + T cells can be imaged by immunoPET with the help of synTacs, MHC-based tools that bind to relevant T-cell receptors.

Purpose: Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. There are institutional initiatives to replace radionuclide sources with lower-energy X-ray sources amidst concerns of radiological terrorism. As researchers transition, there are questions whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays, since different energy may cause different biological effects. We, therefore, sought to compare the effects of orthovoltage X-rays and 137Cs γ-rays using mouse models of acute radiation syndrome. Experimental Design: 137Cs γ-rays were compared with Orthovoltage X-rays, generated at 300 kVp, 10 mA with 1 mm Cu or Thoraeus filtration. We assessed 30-day overall survival following whole-body irradiation and calculated LD50 by logistic regression. Comparing equivalent doses delivered with different average energies (Ē), we assessed bone marrow, spleen, and intestinal histology and flow cytometry. Results: The LD50 doses are 6.7 Gy, 7.4 Gy and 8.1 Gy with 1 mm Cu filtered (Ē=120 keV), and Thoraeus filtered X-rays (Ē=160 keV), and 137Cs (E=662 keV), respectively. At constant dose, hematopoietic injury was most severe with 1 mm Cu filtered X-rays with the greatest reduction in bone marrow cellularity, stem and progenitor populations, and intestinal crypts and OLFM4+ intestinal stem cells. Thoraeus filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage. Conclusions: Our study reveals a dichotomy between physical dose and biological effect relevant as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose-reduction to achieve comparable biological effects. Competing Interest Statement C.G. is a consultant for Varian Medical Systems and Janssen Pharmaceuticals and has received research support from Janssen Pharmaceuticals and Celldex Therapeutics. R.K. is co-founder of Ceramedix Holdings Inc. W.T. has received research support from Varian Medical Systems. The other authors declare no potential conflicts of interest.