Evaluation of the Effects of Exposure to Power‐Frequency Magnetic Fields on the Differentiation of Hematopoietic Stem/Progenitor Cells Using Human‐Induced Pluripotent Stem Cells

Abstract

The causal association between exposure to power‐frequency magnetic fields (MFs) and childhood leukemia has been under discussion. Although evidence from experimental studies is required for a conclusion to be reached, only a few studies have focused on the effects of MF exposure on the human hematopoietic system directly related to leukemogenesis. Here, we established an in vitro protocol to simulate the differentiation of human mesodermal cells to hematopoietic stem progenitor cells (HSPCs) using human‐induced pluripotent stem cells. Furthermore, we introduced MF in the protocol to study the effects of exposure. After a continuous exposure to 0–300 mT of 50‐Hz MFs during the differentiation process, the efficiency of differentiation of mesodermal cells into HSPCs was analyzed in a single‐blinded manner. The percentage of emerged HSPCs from mesodermal cells in groups exposed to 50‐Hz MFs indicated a lack of significant changes compared with those in the sham‐exposed group. These results suggest that exposure to 50‐Hz MFs up to 300 mT does not affect the differentiation of human mesodermal cells to HSPCs, which may be involved in the initial process of leukemogenesis. © 2022 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.

Evaluation of the Effects of Power‐Frequency Magnetic Field Exposure on B‐Cell Differentiation From Human Hematopoietic Stem/Progenitor Cells

“…Given that B‐cell differentiation from hCD34 + cells is supported by hMSCs and mesenchymal cells derived from hMSCs via physical contact and production of cytokines [Ichii et al, 2010], the results of this study may also indicate that exposure to 50 Hz MF at 300 mT does not affect the abilities of hMSCs and mesenchymal cells. In conjunction with our previous report [Takahashi and Furuya, 2022], we determined the influence of 50 Hz MF on the differentiation from human mesodermal cells to B‐cell lineages. These findings will be useful to draw conclusions regarding the causal relationship between exposure to power‐frequency MFs and childhood leukemia.…”

“…We and colleagues have developed in vivo and in vitro experimental systems with human cells, especially primary stem cells and induced pluripotent stem cells, and have used them to evaluate the biological effects of MF [Takahashi et al, 2017; Saito, 2021; Takahashi and Furuya, 2022]. In this study, we imitated, in vitro, the human B‐cell early differentiation from hematopoietic stem/progenitor cells (HSPCs) using human cord blood‐derived CD34 + (hCD34 + ) cells that have a normal phenotype with the potential to reconstitute hematopoiesis in vivo [Takahashi et al, 2012; Garcia‐Perez et al, 2021].…”

Recent updates of stem cell-based erythropoiesis

“…The hematopoietic differentiation potential of AA-iPSCs was significantly reduced, both quantitatively and qualitatively, compared with that of healthy iPSCs. Takahashi et al produced EBs with iPSCs and treated them with BMP4 and Fibroblast growth factor 2 (FGF2) in suspension for up to four days [ 82 ]. Then, from days 5 to 12, differentiation into HSPCs was established using SCF, VEGF, IL-4, IL-6, FLt3L, thrombopoietin (TPO), Insulin-like Growth Factor 1 (IGF-1), and FGF2 by attaching the EBs onto gelatin-coated dishes.…”

“…Then, from days 5 to 12, differentiation into HSPCs was established using SCF, VEGF, IL-4, IL-6, FLt3L, thrombopoietin (TPO), Insulin-like Growth Factor 1 (IGF-1), and FGF2 by attaching the EBs onto gelatin-coated dishes. The authors also studied the effect of exposure to magnetic fields on HSC differentiation, and found no effect on the differentiation of human HSPCs [ 82 ].…”

“… – 13–16 – HSC [ 80 , 81 ] hiPSC (7F3955‐pMXs#1) BMP4, b-FGF, SCF, IGF-1, FLT3L, VEGF, IL‐3, IL‐6, TPO, etc. – 12 – HSC [ 82 ] hiPSC derived from CD34 + cord blood cells (CD34-iPSCs) or CD36 + erythroblasts (PEB-iPSCs) IL-3, SCF, EPO, etc. transferrin, SCF, IL-3, EPO, etc 18 18 RBC [ 84 ] hiPSC(CD34-4F_iPS, CD34-2F_iPS, NSC-2F-iPS, NSC-1F-iPS, Fib-iPS) hESC (H1) SCF, TPO, FLT3L, BMP4, VEGF, IL-3, IL-6, EPO, etc.…”