Exploring the Treatment of Chemotherapy- Induced Myelosuppression with the Kidney- Tonifying, Essence-Replenishing, and Marrow- Fortifying Method Based on the Hematopoietic Stem Cell Homing Theory

Jiayu He, Chengyulong Zheng, Conghan Jiao, Yanyan Cheng, Yuhe Ruan, Ying Zhang

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¹ First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China,

² National Clinical Research Center for Chinese Medicine, Tianjin 300381, China,

³ Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China,

OTD 2025 , 3(4), 26–39; https://doi.org/10.26689/otd.v3i4.13448

© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Abstract

Chemotherapy-induced myelosuppression is a common dose-limiting toxicity of chemotherapy for malignant tumors, and its core mechanism is closely related to hematopoietic stem cell homing disorder. Chinese medicine attributes chemotherapy-induced myelosuppression to the category of “medullary labor” and believes that “deficiency of kidney essence and drying up of the medulla oblongata” is the main pathogenesis of chemotherapy-induced myelosuppression, which is precisely the same as that of hematopoietic stem cell homing disorders revealed by modern medicine, which involves chemokines such as CXCL12/CXCR4 axis, adhesion molecules such as very late antigen-4 (VLA-4)/vascular cell adhesion molecule (VCAM), and other factors such as the CXCL12/CXCR4 axis, and the CXCL4/VCAM axis. This is highly compatible with modern medicine’s revelation of hematopoietic stem cell homing disorder. By activating signaling pathways such as PI3K/Akt and Wnt/β-catenin, up-regulating chemokine expression, enhancing cell adhesion, improving extracellular matrix remodeling, and alleviating oxidative stress, the method of tonifying the kidneys and filling in the marrow promotes the homing of hematopoietic stem cell through multiple pathways, which provides a new idea for the integration of Chinese and Western medicine in the treatment of chemotherapy-induced myelosuppression.

References

Bray F, Laversanne M, Sung H, et al., 2024, Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer Journal for Clinicians, 74(3): 229–263.

Teng Y, Zhang X, Xia C, et al., 2024, Comparison and Predictive Analysis of Cancer Incidence, Mortality, and Prevalence in China and Globally: An Interpretation of GLOBOCAN 2022 Data. Chinese Journal of Cancer Prevention and Treatment, 31(23): 1413–1420.

Barreto J, McCullough K, Ice L, et al., 2014, Antineoplastic Agents and the Associated Myelosuppressive Effects: A Review. Journal of Pharmacy Practice, 27(5): 440–446.

Epstein R, Weerasinghe R, Parrish A, et al., 2022, Real-world Burden of Chemotherapy-induced Myelosuppression in Patients with Small Cell Lung Cancer: A Retrospective Analysis of Electronic Medical Data from Community Cancer Care Providers. Journal of Medical Economics, 25(1): 108–118.

Miao Y, Li Y, Shen H, et al., 2019, Research Progress of Traditional Chinese Medicine in the Treatment of Chemotherapy-induced Myelosuppression in Malignant Tumors. Jilin Journal of Traditional Chinese Medicine, 39(2): 273–277.

Zhang Z, Zhou J, Peng X, et al., 2024, Completion Rates and Myelosuppression Degrees of Cancer Patients Receiving Radiotherapy or Chemoradiotherapy Unchanged Regardless of Delay Duration after Omicron Infection. Scientific Reports, 14(1): 14226.

Sahin A, Buitenhuis M, 2012, Molecular Mechanisms Underlying Adhesion and Migration of Hematopoietic Stem Cells. Cell Adhesion & Migration, 6(1): 39–48.

Pan X, Naruse C, Matsuzaki T, et al., 2025, Critical Role of the Potential O-linked Glycosylation Sites of CXCR4 in Cell Migration and Bone Marrow Homing of Hematopoietic Stem Progenitor Cells. Stem Cells, 43(6): sxaf025.

Li D, Xue W, Li M, et al., 2018, VCAM-1+ Macrophages Guide the Homing of HSPCs to a Vascular Niche. Nature, 564(7734): 119–124.

Kulkarni R, Kale V, 2020, Physiological Cues Involved in the Regulation of Adhesion Mechanisms in Hematopoietic Stem Cell Fate Decision. Frontiers in Cell and Developmental Biology, 8: 611.

Wu M, Yang H, Liu S, et al., 2025, Enhanced Engraftment of Human Haematopoietic Stem Cells via Mechanical Remodelling Mediated by the Corticotropin-releasing Hormone. Nature Biomedical Engineering, 9(5): 754–771.

Zheng Z, He H, Tang X, et al., 2022, Uncovering the Emergence of HSCs in the Human Fetal Bone Marrow by Single-cell RNA-seq Analysis. Cell Stem Cell, 29(11): 1562–1579.e7.

Chen C, Liu W, Yuan F, et al., 2025, G Protein-coupled Receptor GPR182 Negatively Regulates Sprouting Angiogenesis via Modulating CXCL12-CXCR4 Axis Signaling. Angiogenesis, 28(3): 25.

Broxmeyer H, Christopherson K, 2024, Stromal Cell Derived Factor-1/CXCL12, CXCR4 and CD26 in the Mobilization and Homing of Hematopoietic Stem and Progenitor Cells. Current Medicinal Chemistry – Anti-Inflammatory & Anti-Allergy Agents, 3: 4.

Grenier J, Testut C, Fauriat C, et al., 2021, Adhesion Molecules Involved in Stem Cell Niche Retention During Normal Haematopoiesis and in Acute Myeloid Leukaemia. Frontiers in Immunology, 12: 756231.

Tang C, 2018, Study on the Regulation of Hematopoietic Stem Cell Function by Physiological and Pathological Bone Marrow Microenvironment and Its Mechanism, thesis, Shanghai Jiao Tong University.

Wu G, Gao R, Zhang W, et al., 2025, Protective Effect of Periplaneta americana Extract on Cyclophosphamide-induced Myelosuppression in Mice. Chinese Journal of Modern Applied Pharmacy, 42(3): 341–351.

Xu C, Lu T, Lv X, et al., 2023, Role of the Bone Marrow Vascular Niche in Chemotherapy for MLL-AF9-induced Acute Myeloid Leukemia. Blood Science, 5(2): 92–100.

Wang A, Zhong H, 2018, Roles of the Bone Marrow Niche in Hematopoiesis, Leukemogenesis, and Chemotherapy Resistance in Acute Myeloid Leukemia. Hematology, 23(10): 729–739.

Zhou Y, Cao H, Li W, et al., 2018, The CXCL12 (SDF-1)/CXCR4 Chemokine Axis: Oncogenic Properties, Molecular Targeting, and Synthetic and Natural Product CXCR4 Inhibitors for Cancer Therapy. Chinese Journal of Natural Medicines, 16(11): 801–810.

Haltalli M, Watcham S, Wilson N, et al., 2020, Manipulating Niche Composition Limits Damage to Haematopoietic Stem Cells during Plasmodium Infection. Nature Cell Biology, 22(12): 1399–1410.

Sun Y, 2018, Mechanism of Cell Autophagy Affecting Chemotherapy Resistance in Ovarian Cancer and Related Clinical Research, thesis, Fujian Provincial Hospital.

Cook E, Luo M, Rauh M, 2020, Clonal Hematopoiesis and Inflammation: Partners in Leukemogenesis and Comorbidity. Experimental Hematology, 83: 85–94.

Chen K, Ben H, Mao Z, 2020, Romidepsin Combined with Cytarabine Mediates Histone H3K14 Acetylation to Enhance CASP3 Transcription Activity in Lung Adenocarcinoma Cells. Chinese Journal of Biochemistry and Molecular Biology, 36(3): 319–327.

Sighinolfi S, Aprile A, Beretta S, et al., 2023, Intracellular Iron Controls HSC Metabolism by Affecting Mitochondrial Fitness. Blood, 142(Suppl. 1): 2470.

Shao L, Wang Y, Chang J, et al., 2013, Hematopoietic Stem Cell Senescence and Cancer Therapy-induced Long-term Bone Marrow Injury. Translational Cancer Research, 2(5): 397–411.

Chen J, 2015, The Role and Mechanism of Notch Recombinant Ligand D1R in Promoting Hematopoietic Reconstruction, thesis, Fourth Military Medical University.

Duda D, Kozin S, Kirkpatrick N, et al., 2011, CXCL12 (SDF-1α)-CXCR4/CXCR7 Pathway Inhibition: An Emerging Sensitizer for Anticancer Therapies? Clinical Cancer Research, 17(8): 2074–2080.

Xie M, Sun Z, Pang Y, 2024, Latest Research Progress of Eltrombopag in the Treatment of Adult Primary Immune Thrombocytopenia. Chinese Journal of Experimental Hematology, 32(5): 1622–1625.

Han L, Long Q, Li S, et al., 2020, Senescent Stromal Cells Promote Cancer Resistance through SIRT1 Loss-potentiated Overproduction of Small Extracellular Vesicles. Cancer Research, 80(16): 3383–3398.

Lu W, Liu K, Wang W, et al., 2015, Long-term Treatment with Rosiglitazone Delays Hematopoietic Recovery in Response to Stress. Blood, 126(23): 4769.

Tian D, 2017, Suwen (Plain Questions). People’s Medical Publishing House, 2017: 165.

Tian D, Liu G, 2017, Ling Shu (Spiritual Pivot). People’s Medical Publishing House, 2017: 122.

Tang R, 1999, Essentials of Integrating Chinese and Western Medical Classics. China Press of Traditional Chinese Medicine, 1999: 6–66.

Ding G, 2013, Annotated and Collated Treatise on the Origins and Manifestations of Various Diseases. People’s Medical Publishing House, 2013: 60–113 + 130 + 275 + 379 + 574 + 708 + 767 + 1019.

Zhang J, Li J, 2023, Jingyue Quanshu (Complete Works of Zhang Jingyue). People’s Medical Publishing House, 2023: 692.

Ye T, Su L, 2018, Linzheng Zhinan Yi’an (Case Records as a Guide to Clinical Practice). People’s Medical Publishing House, 2018: 464.

Wei W, 2019, Mechanism Study of the “Kidney-tonifying and Marrow-replenishing Method” Promoting Bone Marrow Mesenchymal Stem Cell Transplantation for Liver Cirrhosis Based on the SDF-1/CXCR4 Axis, thesis, Guangxi University of Chinese Medicine.

Wu S, 2008, The Effects of “Warming, Clearing, and Guiding” Methods on Regulating Hematopoietic Stem Cell Homing and GVHD in Transplanted Mice, thesis, Southern Medical University.

Huang X, Luo Z, 2012, Research on the Identity of Kidney Essence and Stem Cells and Its Application Prospects. Chinese Journal of Ethnomedicine and Ethnopharmacy, 21(10): 14–15.

Qian T, He Y, Han C, et al., 2024, Current Status and Prospects of Traditional Chinese Medicine Combined with Stem Cell Therapy for Chronic Kidney Disease. Frontiers in Pharmacology, 15: 1505206.

Wang K, 2021, Study on the Effect of Bushen Huoxue Tiaoying Huatan Decoction on the Homing of Bone Marrow Mesenchymal Stem Cells in Asthma Based on miRNA-139-5p Regulating the Notch Pathway, thesis, Anhui University of Chinese Medicine.

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