PMID- 37848990
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231118
IS  - 1477-3155 (Electronic)
IS  - 1477-3155 (Linking)
VI  - 21
IP  - 1
DP  - 2023 Oct 18
TI  - Exosomes from umbilical cord-derived mesenchymal stem cells combined with gelatin 
      methacryloyl inhibit vein graft restenosis by enhancing endothelial functions.
PG  - 380
LID - 10.1186/s12951-023-02145-1 [doi]
LID - 380
AB  - BACKGROUND: The prevalence of coronary artery disease is increasing. As a common 
      treatment method, coronary artery bypass transplantation surgery can improve 
      heart problems while also causing corresponding complications. Venous graft 
      restenosis is one of the most critical and intractable complications. Stem 
      cell-derived exosomes could have therapeutic promise and value. However, as 
      exosomes alone are prone to inactivation and easy removal, this therapeutic 
      method has not been widely used in clinical practice. Methacrylated gelatin 
      (GelMA) is a polymer with a loose porous structure that maintains the biological 
      activity of the exosome and can control its slow release in vivo. In this study, 
      we combined human umbilical cord mesenchymal stem cell-derived exosomes 
      (hUCMSC-Exos) and GelMA to explore their effects and underlying mechanisms in 
      inhibiting venous graft restenosis. RESULTS: Human umbilical cord mesenchymal 
      stem cells (hUCMSCs) were appraised using flow cytometry. hUCMSC-Exos were 
      evaluated via transmission electron microscopy and western blotting. hUCMSC-Exos 
      embedded in a photosensitive GelMA hydrogel (GelMA-Exos) were applied topically 
      around venous grafts in a rat model of cervical arteriovenous transplantation, 
      and their effects on graft reendothelialization and restenosis were evaluated 
      through ultrasonic, histological, and immunofluorescence examinations. 
      Additionally, we analyzed the material properties, cellular reactions, and 
      biocompatibility of the hydrogels. We further demonstrated that the topical 
      application of GelMA-Exos could accelerate reendothelialization after autologous 
      vein transplantation and reduce restenosis in the rat model. Notably, GelMA-Exos 
      caused neither damage to major organs in mice nor excessive immune rejection. The 
      uptake of GelMA-Exos by endothelial cells stimulated cell proliferation and 
      migration in vitro. A bioinformatic analysis of existing databases revealed that 
      various cell proliferation and apoptosis pathways, including the mammalian target 
      of rapamycin (mTOR)-phosphoinositide 3-kinase (PI3K)-AKT signaling pathways, 
      might participate in the underlying regulatory mechanism. CONCLUSIONS: Compared 
      with the tail vein injection of hUCMSC-Exos, the local application of a mixture 
      of hUCMSC-Exos and GelMA was more effective in promoting endothelial repair of 
      the vein graft and inhibiting restenosis. Therefore, the proposed 
      biomaterial-based therapeutic approach is a promising treatment for venous graft 
      restenosis.
CI  - (c) 2023. BioMed Central Ltd., part of Springer Nature.
FAU - Deng, Yuhang
AU  - Deng Y
AD  - Department of Cardiac Surgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      230001, Anhui, China.
FAU - Li, Yiming
AU  - Li Y
AD  - Department of Cardiac Surgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      230001, Anhui, China.
FAU - Chu, Zhuyang
AU  - Chu Z
AD  - Department of Cardiac Surgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      230001, Anhui, China.
FAU - Dai, Chun
AU  - Dai C
AD  - Department of Cardiac Surgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      230001, Anhui, China.
FAU - Ge, Jianjun
AU  - Ge J
AD  - Department of Cardiac Surgery, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei, 
      230001, Anhui, China. slgejianjun@outlook.com.
LA  - eng
PT  - Journal Article
DEP - 20231018
PL  - England
TA  - J Nanobiotechnology
JT  - Journal of nanobiotechnology
JID - 101152208
RN  - 0 (gelatin methacryloyl)
RN  - 9000-70-8 (Gelatin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Rats
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Gelatin
MH  - *Exosomes/metabolism
MH  - Endothelial Cells
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Mesenchymal Stem Cells
MH  - Umbilical Cord
MH  - Human Umbilical Vein Endothelial Cells
MH  - Mammals
PMC - PMC10583421
OTO - NOTNLM
OT  - Exosomes
OT  - Intimal hyperplasia
OT  - Mesenchymal stem cells
OT  - Photosensitive hydrogel
OT  - Restenosis
COIS- The authors declare no competing interests.
EDAT- 2023/10/18 06:43
MHDA- 2023/10/23 01:18
PMCR- 2023/10/18
CRDT- 2023/10/18 00:03
PHST- 2023/07/27 00:00 [received]
PHST- 2023/10/09 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/18 06:43 [pubmed]
PHST- 2023/10/18 00:03 [entrez]
PHST- 2023/10/18 00:00 [pmc-release]
AID - 10.1186/s12951-023-02145-1 [pii]
AID - 2145 [pii]
AID - 10.1186/s12951-023-02145-1 [doi]
PST - epublish
SO  - J Nanobiotechnology. 2023 Oct 18;21(1):380. doi: 10.1186/s12951-023-02145-1.