Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,...Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,and high cost.To overcome these challenges,we developed Epimedium-derived nanovesicles(ENVs)from the traditional Chinese medicinal herb Epimedium,addressing the solubility and bioavailability issues associated with conventional extracts.ENVs encapsulate bioactive constituents,including icariin and hematopoiesis-promoting ceramides.In a cyclophosphamide(CTX)-induced myelosuppression mouse model,prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression,significantly outperforming the Epimedium-based herbal extract“Joungal”(Shengbai Formula)despite equivalent icariin content.Notably,ENVs promoted hematopoietic stem cell(HSC)proliferation—an outcome rarely achieved with existing therapies.Mechanistically,ENVs modulated the gut microbiota,enriching lactobacillus species and enhancing lactate production.This microbiota-driven lactate signaling stimulated LepR+mesenchymal stem cells(MSCs)in the bone marrow niche to secrete stromal cellderived factor-1(SDF-1)and stem cell factor(SCF),thereby supporting HSC expansion and restoring hematopoietic function.In vivo safety evaluations confirmed the excellent biocompatibility of ENVs.Our findings uncover a gut-lactate-bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration.This work introduces a cost-effective,scalable,and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.展开更多
基金supported by National Natural Science Foundation of China(Nos.82104445 and 82470182]Basic Scientific Research Funds of Department of Education of Zhejiang Province(No.KYZD2024013)+2 种基金The Startup Foundation of Zhejiang Provincial People’s Hospital(Nos.C-2023-QDJJ12 and C-2024-ZZJJ05)Science and Technology Plan Project of Traditional Chinese Medicine in Zhejiang Province(No.2025ZR007)The National Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-24044).
文摘Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,and high cost.To overcome these challenges,we developed Epimedium-derived nanovesicles(ENVs)from the traditional Chinese medicinal herb Epimedium,addressing the solubility and bioavailability issues associated with conventional extracts.ENVs encapsulate bioactive constituents,including icariin and hematopoiesis-promoting ceramides.In a cyclophosphamide(CTX)-induced myelosuppression mouse model,prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression,significantly outperforming the Epimedium-based herbal extract“Joungal”(Shengbai Formula)despite equivalent icariin content.Notably,ENVs promoted hematopoietic stem cell(HSC)proliferation—an outcome rarely achieved with existing therapies.Mechanistically,ENVs modulated the gut microbiota,enriching lactobacillus species and enhancing lactate production.This microbiota-driven lactate signaling stimulated LepR+mesenchymal stem cells(MSCs)in the bone marrow niche to secrete stromal cellderived factor-1(SDF-1)and stem cell factor(SCF),thereby supporting HSC expansion and restoring hematopoietic function.In vivo safety evaluations confirmed the excellent biocompatibility of ENVs.Our findings uncover a gut-lactate-bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration.This work introduces a cost-effective,scalable,and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.
