Nonthermal radiofrequency radiation promotes hematopoietic stem and progenitor cells function by regulating Ca2+ efflux

Abstract

Background: Hematopoietic stem and progenitor cells (HSPCs) are crucial for blood production and regeneration. While their function is known to be regulated by diverse physical cues, the impact of pervasive radiofrequency electromagnetic fields (RF-EMF), particularly through non-thermal radiofrequency radiation (RFR) mechanisms, remains poorly understood. Methods: We conducted colony-forming unit (CFU) assay in vitro and competitive transplantation assay in vivo to evaluate whether RFR influences hematopoiesis reconstitution capacity. Subsequently, the effects of RFR preconditioning on hematopoietic injury induced by ionizing radiation in mice were assessed by continuously monitoring the peripheral blood, HSPCs number, and colony-forming units. The influence of RFR on radioprotection unit frequency was evaluated using multiple gradients, non-competitive mouse transplantation models. Seahorse XF assays were employed to characterize cellular energy metabolic status, while specific fluorescent probes were utilized to detect calcium ion (Ca2+) levels in distinct cellular compartments using flow cytometry. Transcriptomic profiling was used to uncover the underlying mechanisms. HSPCs were pretreated with plasma membrane Ca2+-ATPase (PMCA) inhibitor prior to RFR exposure, and Seahorse assays along with CFU assay and competitive transplantation assay were performed to compare whether PMCA inhibition could abrogate RFR-induced HSPCs function change. To investigate the mechanism by which RFR enhanced PMCA activity inducing Ca2+ efflux, we performed fluorescence recovery after photobleaching (FRAP) assays to detect membrane fluidity. Results: Non-thermal 2856 MHz RFR enhanced HSPCs colony formation activity and reconstitution capacity, without compromising the multilineage differentiation homeostasis. RFR preconditioning accelerated hematopoietic recovery following ionizing radiation and increased radioprotection unit frequency. Mechanistically, RFR increased plasma membrane fluidity which potentiates PMCA activity, resulting in elevated Ca2+ efflux and reduced intracellular Ca2+ levels. These cellular alterations ultimately contributed to maintaining HSPCs in a low metabolic state, and consequently improving their functional capacity. Pharmacological inhibition of PMCA abolished both the functional enhancement and metabolic suppression. Conclusion: Our results provided the first evidence that non-thermal RFR can improve HSPCs function. The central mechanism involved RFR-induced plasma membrane fluidity, activation of PMCA, thus accelerating Ca2+ efflux and maintaining HSPCs in a metabolically quiescent state. This work provided transformative insights into electromagnetic field biology and potential transplantation strategies for radiation-induced hematopoietic injury.

AI evidence extraction

Main findings

Non-thermal 2856 MHz radiofrequency radiation (RFR) increased HSPCs colony formation and hematopoietic reconstitution capacity in mouse models without disrupting multilineage differentiation homeostasis. RFR preconditioning accelerated hematopoietic recovery after ionizing radiation and increased radioprotection unit frequency. Mechanistically, RFR increased plasma membrane fluidity, potentiated PMCA activity, increased Ca2+ efflux and reduced intracellular Ca2+, and maintained HSPCs in a low metabolic state; PMCA inhibition abolished these effects.

Outcomes measured

• HSPCs colony-forming unit (CFU) activity
• Hematopoietic reconstitution capacity (competitive transplantation)
• Multilineage differentiation homeostasis
• Peripheral blood recovery after ionizing radiation
• HSPCs number after ionizing radiation
• Radioprotection unit frequency
• Cellular energy metabolism (Seahorse XF assays)
• Intracellular and compartmental Ca2+ levels (flow cytometry probes)
• Transcriptomic profiling
• Plasma membrane Ca2+-ATPase (PMCA) activity (inferred via inhibitor experiments)
• Membrane fluidity (FRAP)

Limitations

• Sample size not reported in abstract
• Exposure metrics beyond frequency (e.g., SAR, power density, duration) not reported in abstract
• Findings are from mouse/in vitro and mouse in vivo models; human relevance not addressed in abstract

Suggested hubs

• mechanisms-calcium-signaling (0.9)
  Central mechanism involves PMCA-mediated Ca2+ efflux and reduced intracellular Ca2+.
• rf-nonthermal-mechanisms (0.85)
  Study explicitly investigates non-thermal RFR biological effects and mechanisms.
• radiation-countermeasures (0.6)
  Assesses RFR preconditioning for recovery after ionizing radiation-induced hematopoietic injury.

{
    "study_type": "animal",
    "exposure": {
        "band": "microwave",
        "source": null,
        "frequency_mhz": 2856,
        "sar_wkg": null,
        "duration": null
    },
    "population": "Mouse hematopoietic stem and progenitor cells (HSPCs); mouse transplantation models; mice with ionizing radiation-induced hematopoietic injury",
    "sample_size": null,
    "outcomes": [
        "HSPCs colony-forming unit (CFU) activity",
        "Hematopoietic reconstitution capacity (competitive transplantation)",
        "Multilineage differentiation homeostasis",
        "Peripheral blood recovery after ionizing radiation",
        "HSPCs number after ionizing radiation",
        "Radioprotection unit frequency",
        "Cellular energy metabolism (Seahorse XF assays)",
        "Intracellular and compartmental Ca2+ levels (flow cytometry probes)",
        "Transcriptomic profiling",
        "Plasma membrane Ca2+-ATPase (PMCA) activity (inferred via inhibitor experiments)",
        "Membrane fluidity (FRAP)"
    ],
    "main_findings": "Non-thermal 2856 MHz radiofrequency radiation (RFR) increased HSPCs colony formation and hematopoietic reconstitution capacity in mouse models without disrupting multilineage differentiation homeostasis. RFR preconditioning accelerated hematopoietic recovery after ionizing radiation and increased radioprotection unit frequency. Mechanistically, RFR increased plasma membrane fluidity, potentiated PMCA activity, increased Ca2+ efflux and reduced intracellular Ca2+, and maintained HSPCs in a low metabolic state; PMCA inhibition abolished these effects.",
    "effect_direction": "benefit",
    "limitations": [
        "Sample size not reported in abstract",
        "Exposure metrics beyond frequency (e.g., SAR, power density, duration) not reported in abstract",
        "Findings are from mouse/in vitro and mouse in vivo models; human relevance not addressed in abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "radiofrequency electromagnetic fields",
        "non-thermal radiofrequency radiation",
        "2856 MHz",
        "microwave",
        "hematopoietic stem and progenitor cells",
        "colony-forming unit",
        "competitive transplantation",
        "radiation-induced hematopoietic injury",
        "Ca2+ efflux",
        "PMCA",
        "membrane fluidity",
        "metabolic quiescence"
    ],
    "suggested_hubs": [
        {
            "slug": "mechanisms-calcium-signaling",
            "weight": 0.90000000000000002220446049250313080847263336181640625,
            "reason": "Central mechanism involves PMCA-mediated Ca2+ efflux and reduced intracellular Ca2+."
        },
        {
            "slug": "rf-nonthermal-mechanisms",
            "weight": 0.84999999999999997779553950749686919152736663818359375,
            "reason": "Study explicitly investigates non-thermal RFR biological effects and mechanisms."
        },
        {
            "slug": "radiation-countermeasures",
            "weight": 0.59999999999999997779553950749686919152736663818359375,
            "reason": "Assesses RFR preconditioning for recovery after ionizing radiation-induced hematopoietic injury."
        }
    ]
}

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