PMID- 33470478
OWN - NLM
STAT- MEDLINE
DCOM- 20211108
LR  - 20211108
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 45
IP  - 5
DP  - 2021 May
TI  - Potential surrogate quantitative immunomodulatory potency assay for monitoring 
      human umbilical cord-derived mesenchymal stem cells production.
PG  - 1072-1081
LID - 10.1002/cbin.11553 [doi]
AB  - Mesenchymal stem cells (MSCs) play an important role as immune modulator through 
      interaction with several immune cells, including macrophages. In this study, the 
      immunomodulatory potency of human umbilical cord-derived mesenchymal stem cells 
      (hUC-MSCs) was demonstrated in the in vivo middle cerebral artery occlusion 
      (MCAo)-induced brain injury rat model and in vitro THP-1-derived macrophages 
      model. At 24 h after induction of MCAo, hUC-MSCs was administered via tail vein 
      as a single dose. Remarkably, hUC-MSCs could inhibit M1 polarization and promote 
      M2 polarization of microglia in vivo after 14 days induction of MCAo. Compared 
      with THP-1-derived macrophages which had been stimulated by lipopolysaccharide, 
      the secretion of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and 
      interferon-gamma inducible protein (IP-10), were significantly reduced in the 
      presence of hUC-MSCs. Moreover, the secretion of anti-inflammatory cytokine, 
      interleukin-10 (IL-10), was significantly increased after cocultured with 
      hUC-MSCs. Prostaglandins E2 (PGE2), secreted by hUC-MSCs, is one of the crucial 
      immunomodulatory factors and could be inhibited in the presence of COX2 
      inhibitor, NS-398. PGE2 inhibition suppressed hUC-MSCs immunomodulatory 
      capability, which was restored after addition of synthetic PGE2, establishing the 
      minimum amount of PGE2 required for immunomodulation. In conclusion, our data 
      suggested that PGE2 is a crucial potency marker involved in the therapeutic 
      activity of hUC-MSCs through macrophages immune response modulation and cytokines 
      regulation. This study provides the model for the development of a surrogate 
      quantitative potency assay of immunomodulation in stem cells production.
CI  - (c) 2021 International Federation for Cell Biology.
FAU - Teng, Sen-Wen
AU  - Teng SW
AD  - Department of Obstetrics and Gynecology, Cardinal Tien Hospital, New Taipei, 
      Taiwan.
AD  - School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan.
FAU - Sung, Hsin-Yu
AU  - Sung HY
AD  - Meribank Biotech Co., Ltd., Taipei, Taiwan.
FAU - Wen, Yu-Chieh
AU  - Wen YC
AD  - Meridigen Biotech Co., Ltd., Taipei, Taiwan.
FAU - Chen, Ssu-Yu
AU  - Chen SY
AD  - Meridigen Biotech Co., Ltd., Taipei, Taiwan.
FAU - Lovel, Ronald
AU  - Lovel R
AD  - Meridigen Biotech Co., Ltd., Taipei, Taiwan.
FAU - Chang, Wen-Ying
AU  - Chang WY
AD  - Meribank Biotech Co., Ltd., Taipei, Taiwan.
FAU - Wu, Tang Bo-Chung
AU  - Wu TB
AD  - Meridigen Biotech Co., Ltd., Taipei, Taiwan.
FAU - Hsuan, Yogi Cheng-Yo
AU  - Hsuan YC
AD  - Meribank Biotech Co., Ltd., Taipei, Taiwan.
AD  - Meridigen Biotech Co., Ltd., Taipei, Taiwan.
FAU - Lin, Willie
AU  - Lin W
AUID- ORCID: 0000-0003-0169-5927
AD  - Meridigen Biotech Co., Ltd., Taipei, Taiwan.
LA  - eng
GR  - Meridigen Biotech Co., Ltd./
PT  - Journal Article
DEP - 20210202
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Cytokines)
RN  - 0 (Prostaglandins E)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/metabolism/*therapy
MH  - Cell Differentiation/immunology
MH  - Coculture Techniques/methods
MH  - Cytokines/metabolism
MH  - Dinoprostone/immunology/*metabolism
MH  - Female
MH  - Fetal Blood/metabolism
MH  - Human Embryonic Stem Cells/metabolism
MH  - Humans
MH  - Immunity/drug effects
MH  - Immunomodulation/immunology
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/metabolism/physiology
MH  - Microglia/metabolism
MH  - Prostaglandins E/immunology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - immunomodulation
OT  - mesenchymal stem cells
OT  - potency
OT  - prostaglandins E2
EDAT- 2021/01/21 06:00
MHDA- 2021/11/09 06:00
CRDT- 2021/01/20 08:43
PHST- 2020/12/01 00:00 [revised]
PHST- 2020/08/19 00:00 [received]
PHST- 2020/12/27 00:00 [accepted]
PHST- 2021/01/21 06:00 [pubmed]
PHST- 2021/11/09 06:00 [medline]
PHST- 2021/01/20 08:43 [entrez]
AID - 10.1002/cbin.11553 [doi]
PST - ppublish
SO  - Cell Biol Int. 2021 May;45(5):1072-1081. doi: 10.1002/cbin.11553. Epub 2021 Feb 
      2.