Assessment of individual hematopoietic stem cell response to gamma exposure using humanized mice

Atamanyuk NI1, Pryakhin EA1, Styazhkina EV1,2, Obvintseva NA1, Tryapitsyna GA1,2, Peretykin AA1, Andreev SS1, Aldibekova AE1, Akleyev AV1,2
About authors

1 Urals Research Center for Radiation Medicine of the Federal Medical Biological Agency, Chelyabinsk, Russia

2 Chelyabinsk State University, Chelyabinsk, Russia

Correspondence should be addressed: Natalia I. Atamanyuk
Vorovskogo, 68А, Chelyabinsk, 454141, Russia; ur.liam@arhlup_ativ

About paper

Funding: the study was performed as part of the State Assignment of FMBA of Russia.

Acknowledgments: the authors would like to thank A.V. Sherstobitov (Regional Perinatal Center, Chelyabinsk) for his help in organizing and cord blood sampling.

Author contribution: Atamanyuk NI — planning and conducting experiments, manuscript writing; Pryakhin EA — study planning and management, manuscript writing; Styazhkina EV — HSC isolation, data analysis; Obvintseva NA — measurement, flow cytometry; Tryapitsyna GA — data analysis; Peretykin AA — animal exposure, dosimetry studies; Andreev SS — animal handling, measurement; Aldibekova AE — animal handling; Akleyev AV — general management.

Compliance with the ethical standards: the study was approved by the Ethics Committee of the Urals Research Center for Radiation Medicine (protocol № 2 of 27 June 2022). Cord blood sampling was performed after obtaining the informed consent from donors at the Chelyabinsk Regional Perinatal Center. Peripheral blood samples were provided by the Blood Transfusion Station of FMBA of Russia (Chelyabinsk) in accordance with the Decree of the Government of the Russian Federation № 331 of 12 April 2013. Animals were handled in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (1986, Strasbourg), Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.

Received: 2023-02-22 Accepted: 2023-03-09 Published online: 2023-03-11

Assessment of individual responses of cells, tissues and the whole body to radiation exposure is an important challenge for radiobiology and radiation safety. The study was aimed to develop the method for estimation of the human hematopietic stem cell (HSC) individual response in the humanized mouse model. The cord blood or peripheral blood HSCs were administered to the NOD SCID immunodeficient mice. The number of maturing HSCs (CD34+ cells) and mature CD45+ leukocytes was assesed after the acute gamma exposure to the doses of 0.5 Gy, 1 Gy, and 1.5 Gy, along with the HSC share among all CD45low/+ cells within three days (period of maximum mortality) and 14 days (period of active restoration) after exposure. The relationship between the indicato values and the exposure dose was calculated by regression analysis. There was exponential relationship between the human HSC survival rate in humanized mice and the dose on day three after exposure (R2 = 0.93; F = 211; p < 0.01), while the relationship between the number of HSCs and the dose on day 14 after exposure was linear (R2 = 0.65; F = 12.9; p = 0.01). The C14/3 coefficient calculated as a ratio of the HSC share among all human CD45low/+ cells on day 14 after exposure to the same parameter on day three after exposure was proposed as an indicator of HSC mortality and HSC number restoration. C14/3 negatively correlated with the exposure dose (R2 = 0.57; F = 13.3; p = 0.004), it was higher in radioresistant mice and the model of  cysteamine-induced radioresistance in humanized mice. The model mice humanized using the peripheral blood HSCs can be used to assess individual HSC response to acute external gamma exposure based on C14/3 and the data on the HSC survival and restoration.

Keywords: hematopoietic stem cells, acute radiation syndrome, humanized mice, individual radiosensitivity