1. Academic Validation
  2. Electrical Sympathetic Neuromodulation Protects Bone Marrow Niche and Drives Hematopoietic Regeneration during Chemotherapy

Electrical Sympathetic Neuromodulation Protects Bone Marrow Niche and Drives Hematopoietic Regeneration during Chemotherapy

  • Small Methods. 2023 Feb 26;e2201300. doi: 10.1002/smtd.202201300.
Ya-Ting Hsu 1 2 Li-Hsien Chen 3 Ya-Hui Liu 4 Shih-Kai Chu 5 Tsai-Yun Chen 2 Kuen-Jer Tsai 1 6 Meng-Ru Shen 1 3 7 Wentai Liu 8 9 10 11
Affiliations

Affiliations

  • 1 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan.
  • 2 Division of Hematology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704302, Taiwan.
  • 3 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan.
  • 4 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704302, Taiwan.
  • 5 Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan, 704302, Taiwan.
  • 6 Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University, Tainan, 704302, Taiwan.
  • 7 Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704302, Taiwan.
  • 8 Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
  • 9 California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
  • 10 Department of Electrical and Computer Engineering, University of California, Los Angeles, CA, 90095, USA.
  • 11 Brain Research Institute, University of California, Los Angeles, CA, 90095, USA.
Abstract

The sympathetic nervous system (SNS) of the bone marrow regulates the regeneration and mobilization of hematopoietic stem cells. Chemotherapy can damage bone marrow SNS, which impairs hematopoietic regeneration and aggravates hematologic toxicities. This leads to long-term bone marrow niche damage and increases mortality in patients undergoing chemotherapy. Electrical neuromodulation has been used to improve functional recovery after peripheral nerve injury. This study demonstrates that electrical sympathetic neuromodulation (ESN) of bone marrow can protect the bone marrow niche from chemotherapy-induced injury. Using carboplatin-treated rats, the SNS via the sciatic nerve innervating the femoral marrow with the effective protocol for bone marrow sympathetic activation is electrically stimulated. ESN can mediate several hematopoietic stem cells maintenance factors and promote hematopoietic regeneration after chemotherapy. It also activates adrenergic signals and reduces the release of pro-inflammatory cytokines, particularly interleukin-1 β, which contribute to chemotherapy-related nerve injury. Consequently, the severity of chemotherapy-related leukopenia, thrombocytopenia, and mortality can be reduced by ESN. As a result, in contrast to current drug-based treatment, such as granulocyte colony-stimulating factor, ESN can be a disruptive adjuvant treatment by protecting and modulating bone marrow function to reduce hematologic toxicity during chemotherapy.

Keywords

bone marrow niche; chemotherapy-induced nerve damage; electrical neuromodulation; hematopoiesis.

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