Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow-derived mesenchymal stem cells and slow age-related degeneration

Qian Lei; Fei Gao; Teng Liu; Wenxiang Ren; Li Chen; Yulin Cao; Wenlan Chen; Shaojun Guo; Qiong Zhang; Weiqun Chen; Hongxiang Wang; Zhichao Chen; Qiubai Li; Yu Hu; An-Yuan Guo

doi:10.1126/scitranslmed.aaz8697

Extracellular vesicles deposit PCNA to rejuvenate aged bone marrow-derived mesenchymal stem cells and slow age-related degeneration

Sci Transl Med. 2021 Jan 27;13(578):eaaz8697. doi: 10.1126/scitranslmed.aaz8697.

Authors

Qian Lei¹, Fei Gao², Teng Liu³, Wenxiang Ren², Li Chen⁴, Yulin Cao², Wenlan Chen², Shaojun Guo², Qiong Zhang³, Weiqun Chen⁴, Hongxiang Wang⁴, Zhichao Chen², Qiubai Li⁵, Yu Hu⁵, An-Yuan Guo⁶

Affiliations

¹ Institute of Hematology, Union Hospital, Tongji Medical College, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430022, China.
² Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³ Center for Artificial Intelligence Biology, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
⁴ Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
⁵ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. [email protected] [email protected] [email protected].
⁶ Center for Artificial Intelligence Biology, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. [email protected] [email protected] [email protected].

PMID: 33504653
DOI: 10.1126/scitranslmed.aaz8697

Abstract

Stem cell senescence increases alongside the progressive functional declines that characterize aging. The effects of extracellular vesicles (EVs) are now attracting intense interest in the context of aging and age-related diseases. Here, we demonstrate that neonatal umbilical cord (UC) is a source of EVs derived from mesenchymal stem cells (MSC-EVs). These UC-produced MSC-EVs (UC-EVs) contain abundant anti-aging signals and rejuvenate senescing adult bone marrow-derived MSCs (AB-MSCs). UC-EV-rejuvenated AB-MSCs exhibited alleviated aging phenotypes and increased self-renewal capacity and telomere length. Mechanistically, UC-EVs rejuvenate AB-MSCs at least partially by transferring proliferating cell nuclear antigen (PCNA) into recipient AB-MSCs. When tested in therapeutic context, UC-EV-triggered rejuvenation enhanced the regenerative capacities of AB-MSCs in bone formation, wound healing, and angiogenesis. Intravenously injected UC-EVs conferred anti-aging phenotypes including decreased bone and kidney degeneration in aged mice. Our findings reveal that UC-EVs are of high translational value in anti-aging intervention.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow
Cellular Senescence
Extracellular Vesicles*
Mesenchymal Stem Cells*
Mice
Proliferating Cell Nuclear Antigen

Substances

Proliferating Cell Nuclear Antigen