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31 December 2015 Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors
Seishi Kyoizumi, Yoshiko Kubo, Munechika Misumi, Junko Kajimura, Kengo Yoshida, Tomonori Hayashi, Kazue Imai, Waka Ohishi, Kei Nakachi, Lauren F. Young, Jae-Hung Shieh, Malcolm A. Moore, Marcel R. M. van den Brink, Yoichiro Kusunoki
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Abstract

It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34 Lin) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34 Lin cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34 Lin cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34 Lin cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels.

Seishi Kyoizumi, Yoshiko Kubo, Munechika Misumi, Junko Kajimura, Kengo Yoshida, Tomonori Hayashi, Kazue Imai, Waka Ohishi, Kei Nakachi, Lauren F. Young, Jae-Hung Shieh, Malcolm A. Moore, Marcel R. M. van den Brink, and Yoichiro Kusunoki "Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors," Radiation Research 185(1), 69-76, (31 December 2015). https://doi.org/10.1667/RR14209.1
Received: 24 July 2015; Accepted: 1 October 2015; Published: 31 December 2015
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