PMID- 35686052
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231117
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 10
DP  - 2022
TI  - Mesenchymal Stem Cells-Derived Exosomes Ameliorate Ischemia/Reperfusion Induced 
      Acute Kidney Injury in a Porcine Model.
PG  - 899869
LID - 10.3389/fcell.2022.899869 [doi]
LID - 899869
AB  - Exosomes are membrane-enclosed vesicles secreted by cells, containing a variety 
      of biologically active ingredients including proteins, nucleic acids and lipids. 
      In this study, we investigated the therapeutic effects of the exosomes and 
      underlying mechanisms in a miniature pig model of ischemia/reperfusion-induced 
      acute kidney injury (I/R-AKI). The exosomes were extracted from cultured human 
      umbilical cord derived mesenchymal stem cells (hUC-MSCs) and infused into a 
      miniature pig model of I/R AKI. Our results showed that 120 min of unilateral 
      ischemia followed by reperfusion and contralateral nephrectomy resulted in renal 
      dysfunction, severe kidney damage, apoptosis and necroptosis. Intravenous 
      infusion of one dose of exosomes collected from about 4 x 10(8) hUC-MSCs 
      significantly improved renal function and reduced apoptosis and necroptosis. 
      Administration of hUC-MSC exosomes also reduced the expression of some 
      pro-inflammatory cytokines/chemokines, decreased infiltration of macrophages to 
      the injured kidneys and suppressed the phosphorylation of nuclear factor-kappaB and 
      signal transducer and activator of transcription 3, two transcriptional factors 
      related to inflammatory regulation. Moreover, hUC-MSC exosomes could promote 
      proliferation of renal tubular cells, angiogenesis and upregulation of Klotho and 
      Bone Morphogenetic Protein 7, two renoprotective molecules and vascular 
      endothelial growth factor A and its receptor. Collectively, our results suggest 
      that injection of hUC-MSC exosomes could ameliorate I/R-AKI and accelerate renal 
      tubular cell repair and regeneration, and that hUC-MSC exosomes may be used as a 
      potential biological therapy for Acute kidney injury patients.
CI  - Copyright (c) 2022 Huang, Cao, Cui, Ma, Gao, Yu, Shen, Yang, Liu, Qiu, Cai and 
      Zhuang.
FAU - Huang, Jianni
AU  - Huang J
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Cao, Hao
AU  - Cao H
AD  - Department of Cardiac Surgery, Shanghai East Hospital, Tongji University School 
      of Medicine, Shanghai, China.
FAU - Cui, Binbin
AU  - Cui B
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Ma, Xiaoyan
AU  - Ma X
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Gao, Ling
AU  - Gao L
AD  - Translational Medical Center for Stem Cell Therapy and Institute for Regenerative 
      Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 
      China.
FAU - Yu, Chao
AU  - Yu C
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Shen, Fengchen
AU  - Shen F
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Yang, Xinyu
AU  - Yang X
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Liu, Na
AU  - Liu N
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
FAU - Qiu, Andong
AU  - Qiu A
AD  - School of Life Science and Technology, Advanced Institute of Translational 
      Medicine, Tongji University, Shanghai, China.
FAU - Cai, Guangyan
AU  - Cai G
AD  - Department of Nephrology, Chinese PLA General Hospital, Beijing, China.
FAU - Zhuang, Shougang
AU  - Zhuang S
AD  - Department of Nephrology, Shanghai East Hospital, Tongji University School of 
      Medicine, Shanghai, China.
LA  - eng
GR  - R01 DK113256/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20220524
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC9171021
OTO - NOTNLM
OT  - acute kidney injury
OT  - apoptosis
OT  - exosomes
OT  - human umbilical cord derived mesenchymal stem cells
OT  - ischemia/reperfusion
OT  - macrophages
OT  - necroptosis
OT  - transcriptional factors
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/11 06:00
MHDA- 2022/06/11 06:01
PMCR- 2022/01/01
CRDT- 2022/06/10 02:40
PHST- 2022/03/19 00:00 [received]
PHST- 2022/04/26 00:00 [accepted]
PHST- 2022/06/10 02:40 [entrez]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/06/11 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 899869 [pii]
AID - 10.3389/fcell.2022.899869 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2022 May 24;10:899869. doi: 10.3389/fcell.2022.899869. 
      eCollection 2022.