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Research Article

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

Yin Yuan1,2,§, Lijun Chen1,3,§, Jing Yang1, Sining Zhou1, Yangxin Fang1, Qi Zhang1, Ning Zhang1, Yifei Li1, Li Yuan4, Fan Jia5,6(), Shuo Ni7,8(), Charlie Xiang1,3()
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
Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou 310003, China
Innovative Precision Medicine (IPM) Group, Hangzhou 311215, China
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
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
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston MA 02115, USA
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

§ Yin Yuan and Lijun Chen contributed equally to this work.

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In this work, we isolated a kind of mesenchymal stem cells from women’s menstrual blood (MenSCs) and established a bone marrow-targeted cell delivery system (ZAM) via microfluidics. Systematic infusion of ZAMs enhanced the bone marrow homing efficiency of MenSCs and restored bone mass effectively by remodeling mouse bone marrow niche.

Abstract

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 water-in-oil-in-water droplet microfluidics. MenSCs were encapsulated within β-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 (nTreg) 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.

Keywords

mesenchymal stem cellsmicrofluidicsbone marrow homingstem cell nichepostmenopausal osteoporosis

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Nano Research
Volume 17 Issue 8,
August 2024
Pages 7449-7460
DOI: 10.1007/s12274-024-6715-1
Cite this article:
Yuan Y, Chen L, Yang J, et al. Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration. Nano Research, 2024, 17(8): 7449-7460. https://doi.org/10.1007/s12274-024-6715-1
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