Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration  

作　　者：Yin Yuan Lijun Chen Jing Yang Sining Zhou Yangxin Fang Qi Zhang Ning Zhang Yifei Li Li Yuan Fan Jia Shuo Ni Charlie Xiang 

机构地区：[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,National Medical Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [2]Department of Biology,The David H.Koch Institute for Integrative Cancer Research at MIT,Massachusetts Institute of Technology,Cambridge,MA 02139,USA [3]Research Units of Infectious disease and Microecology,Chinese Academy of Medical Sciences,Hangzhou 310003,China [4]Innovative Precision Medicine(IPM)Group,Hangzhou 311215,China [5]MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou 310027,China [6]Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province,Department of Cardiology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China [7]Department of Cancer Immunology and Virology,Dana-Farber Cancer Institute,Boston,MA 02215,USA,Department of Immunology,Harvard Medical School,Boston MA 02115,USA [8]Department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200233,China

出　　处：《Nano Research》2024年第8期7449-7460,共12页纳米研究（英文版）

基　　金：supported by the National Key R&D Program of China(No.2022YFA1105603);the Fundamental Research Funds for the Central Universities(No.2022ZFJH003);National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09201002-005);the National Natural Science Foundation of China(Nos.82200994 and 81900563);CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045);Shanghai Post-doctoral Excellence Program(No.2022428).

摘　　要：Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis treatment.However,limited sources and poor tissue-homing efficiency limit their clinical capabilities.In this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet microfluidics.MenSCs were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for bone.With this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse models.Moreover,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting CCL28.The recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone marrow.This study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.

关 键 词：mesenchymal stem cells MICROFLUIDICS bone marrow homing stem cell niche postmenopausal osteoporosis 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]