PMID- 33779331
OWN - NLM
STAT- MEDLINE
DCOM- 20220204
LR  - 20220204
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 40
IP  - 10
DP  - 2021 Oct
TI  - Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and 
      inflammatory response during spinal cord injury by inhibiting the 
      TLR4/MyD88/NF-kappaB signaling pathway.
PG  - 1612-1623
LID - 10.1177/09603271211003311 [doi]
AB  - Spinal cord injury (SCI) is one of the most common destructive injuries, which 
      may lead to permanent neurological dysfunction. Currently, transplantation of 
      bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows 
      promise as effective therapies. BMSCs secrete various factors that can regulate 
      the microenvironment, which is called paracrine effect. Among these paracrine 
      substances, exosomes are considered to be the most valuable therapeutic factors. 
      Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and 
      inflammation response in the injured spinal cord tissues. In in vitro studies, 
      BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced 
      PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including 
      tumor necrosis factor (TNF)-alpha and IL (interleukin)-1beta and promoted the secretion 
      of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that 
      LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid 
      differentiation factor 88 (MyD88) and nuclear transcription factor-kappaB (NF-kappaB) was 
      significantly downregulated after treatment with BMSCs-derived exosomes. In in 
      vivo studies, we found that hindlimb motor function was significantly improved in 
      SCI rats with systemic administration of BMSCs-derived exosomes. We also observed 
      that the expression of pro-apoptotic proteins and pro-inflammatory factors was 
      significantly decreased, while the expression of anti-apoptotic proteins and 
      anti-inflammatory factors were upregulated in SCI rats after exosome treatment. 
      In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation 
      response induced by injury and promote motor function recovery by inhibiting the 
      TLR4/MyD88/NF-kappaB signaling pathway, which suggests that BMSCs-derived exosomes 
      are expected to become a new therapeutic strategy for SCI.
FAU - Fan, Liying
AU  - Fan L
AUID- ORCID: 0000-0001-5298-7167
AD  - Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China.
FAU - Dong, Jun
AU  - Dong J
AD  - Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China.
FAU - He, Xijing
AU  - He X
AD  - Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China.
FAU - Zhang, Chun
AU  - Zhang C
AD  - Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China.
FAU - Zhang, Ting
AU  - Zhang T
AD  - Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi Province, China.
LA  - eng
PT  - Journal Article
DEP - 20210329
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Myd88 protein, rat)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Bone Marrow Cells/*physiology
MH  - Exosomes/*metabolism
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Male
MH  - Mesenchymal Stem Cells/*physiology
MH  - Myeloid Differentiation Factor 88/genetics/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/*metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
OTO - NOTNLM
OT  - Spinal cord injury
OT  - bone marrow mesenchymal stem cells
OT  - exosomes
OT  - inflammatory response
OT  - the TLR4/MyD88/NF-kappaB pathway
EDAT- 2021/03/30 06:00
MHDA- 2022/02/05 06:00
CRDT- 2021/03/29 12:33
PHST- 2021/03/30 06:00 [pubmed]
PHST- 2022/02/05 06:00 [medline]
PHST- 2021/03/29 12:33 [entrez]
AID - 10.1177/09603271211003311 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2021 Oct;40(10):1612-1623. doi: 10.1177/09603271211003311. Epub 
      2021 Mar 29.