PMID- 38395929
OWN - NLM
STAT- MEDLINE
DCOM- 20240226
LR  - 20240227
IS  - 1477-3155 (Electronic)
IS  - 1477-3155 (Linking)
VI  - 22
IP  - 1
DP  - 2024 Feb 23
TI  - Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal 
      stem cells within a modified gelatine hydrogel promote osteochondral regeneration 
      by enhancing stem cell activity and regulating immunity.
PG  - 74
LID - 10.1186/s12951-024-02333-7 [doi]
LID - 74
AB  - Due to its unique structure, articular cartilage has limited abilities to undergo 
      self-repair after injury. Additionally, the repair of articular cartilage after 
      injury has always been a difficult problem in the field of sports medicine. 
      Previous studies have shown that the therapeutic use of mesenchymal stem cells 
      (MSCs) and their extracellular vesicles (EVs) has great potential for promoting 
      cartilage repair. Recent studies have demonstrated that most transplanted stem 
      cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are 
      subsequently generated play crucial roles in tissue repair. Additionally, MSCs 
      are known to exist under low-oxygen conditions in the physiological environment, 
      and these hypoxic conditions can alter the functional and secretory properties of 
      MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs 
      that are isolated from adipose-derived MSCs cultured under hypoxic conditions 
      (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than 
      those that are isolated from cells cultured under normoxic conditions. Through in 
      vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs 
      exerted enhanced effects on stem cell proliferation, stem cell migration, and 
      bone marrow derived macrophages (BMDMs) M(2) polarization compared to ApoEVs. 
      Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular 
      matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint 
      cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM 
      scaffold provided mechanical support and created a microenvironment that was 
      conducive to cartilage regeneration, and the H-ApoEVs further enhanced the 
      regenerative capacity of endogenous stem cells and the immunomodulatory 
      microenvironment of the joint cavity; thus, this approach significantly promoted 
      cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery 
      system based on a modified gelatine matrix/3D-printed ECM scaffold together with 
      hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs 
      and represents a promising approach for promoting cartilage regeneration.
CI  - (c) 2024. The Author(s).
FAU - Ding, Zhengang
AU  - Ding Z
AD  - Guizhou Medical University, Guiyang, 550004, Guizhou, China.
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Yan, Zineng
AU  - Yan Z
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Yuan, Xun
AU  - Yuan X
AD  - Guizhou Medical University, Guiyang, 550004, Guizhou, China.
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Tian, Guangzhao
AU  - Tian G
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
AD  - School of Medicine, Nankai University, Tianjin, 300071, China.
FAU - Wu, Jiang
AU  - Wu J
AD  - Guizhou Medical University, Guiyang, 550004, Guizhou, China.
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Fu, Liwei
AU  - Fu L
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
AD  - School of Medicine, Nankai University, Tianjin, 300071, China.
FAU - Yin, Han
AU  - Yin H
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - He, Songlin
AU  - He S
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
AD  - School of Medicine, Nankai University, Tianjin, 300071, China.
FAU - Ning, Chao
AU  - Ning C
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Zheng, Yazhe
AU  - Zheng Y
AD  - Guizhou Medical University, Guiyang, 550004, Guizhou, China.
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Zhang, Zhichao
AU  - Zhang Z
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
AD  - School of Medicine, Nankai University, Tianjin, 300071, China.
FAU - Sui, Xiang
AU  - Sui X
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Hao, Libo
AU  - Hao L
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
FAU - Niu, Yuting
AU  - Niu Y
AD  - Central Laboratory, Peking University School and Hospital of Stomatology, 
      Beijing, 100081, People's Republic of China. yuting.niu@bjmu.edu.cn.
FAU - Liu, Shuyun
AU  - Liu S
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China. 
      clear_ann@163.com.
FAU - Guo, Weimin
AU  - Guo W
AD  - Department of Orthopaedic Surgery Guangdong Provincial Key Laboratory of 
      Orthopedics and Traumatology, First Affiliated Hospital Sun Yat-Sen University, 
      Guangzhou, 510080, Guangdong, China. guowm5@mail.sysu.edu.cn.
FAU - Guo, Quanyi
AU  - Guo Q
AD  - Guizhou Medical University, Guiyang, 550004, Guizhou, China. 
      doctorguo_301@163.com.
AD  - Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Laboratory of 
      Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & 
      War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China. 
      doctorguo_301@163.com.
LA  - eng
GR  - 2019YFA0110600/National Key Research and Development Program of China/
PT  - Journal Article
DEP - 20240223
PL  - England
TA  - J Nanobiotechnology
JT  - Journal of nanobiotechnology
JID - 101152208
RN  - 0 (Hydrogels)
RN  - 9000-70-8 (Gelatin)
SB  - IM
MH  - Humans
MH  - Hydrogels
MH  - Tissue Scaffolds/chemistry
MH  - Gelatin
MH  - *Cartilage, Articular
MH  - Stem Cells
MH  - *Mesenchymal Stem Cells
MH  - *Extracellular Vesicles
MH  - Hypoxia
PMC - PMC10885680
OTO - NOTNLM
OT  - 3D printing
OT  - Cartilage injury
OT  - Hypoxia
OT  - Modified gelatine matrix
OT  - Stem cell-derived apoptotic extracellular vesicles
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2024/02/24 11:42
MHDA- 2024/02/26 06:42
PMCR- 2024/02/23
CRDT- 2024/02/23 23:42
PHST- 2023/12/30 00:00 [received]
PHST- 2024/02/09 00:00 [accepted]
PHST- 2024/02/26 06:42 [medline]
PHST- 2024/02/24 11:42 [pubmed]
PHST- 2024/02/23 23:42 [entrez]
PHST- 2024/02/23 00:00 [pmc-release]
AID - 10.1186/s12951-024-02333-7 [pii]
AID - 2333 [pii]
AID - 10.1186/s12951-024-02333-7 [doi]
PST - epublish
SO  - J Nanobiotechnology. 2024 Feb 23;22(1):74. doi: 10.1186/s12951-024-02333-7.