PMID- 24406319
OWN - NLM
STAT- MEDLINE
DCOM- 20140925
LR  - 20220309
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 46
IP  - 1
DP  - 2014 Jan 10
TI  - Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone 
      marrow-derived macrophages.
PG  - e70
LID - 10.1038/emm.2013.135 [doi]
AB  - Mesenchymal stem cells (MSCs) have been widely studied for their applications in 
      stem cell-based regeneration. During myocardial infarction (MI), infiltrated 
      macrophages have pivotal roles in inflammation, angiogenesis and cardiac 
      remodeling. We hypothesized that MSCs may modulate the immunologic environment to 
      accelerate regeneration. This study was designed to assess the functional 
      relationship between the macrophage phenotype and MSCs. MSCs isolated from bone 
      marrow and bone marrow-derived macrophages (BMDMs) underwent differentiation 
      induced by macrophage colony-stimulating factor. To determine the macrophage 
      phenotype, classical M1 markers and alternative M2 markers were analyzed with or 
      without co-culturing with MSCs in a transwell system. For animal studies, MI was 
      induced by the ligation of the rat coronary artery. MSCs were injected within the 
      infarct myocardium, and we analyzed the phenotype of the infiltrated macrophages 
      by immunostaining. In the MSC-injected myocardium, the macrophages adjacent to 
      the MSCs showed strong expression of arginase-1 (Arg1), an M2 marker. In BMDMs 
      co-cultured with MSCs, the M1 markers such as interleukin-6 (IL-6), IL-1beta, 
      monocyte chemoattractant protein-1 and inducible nitric oxide synthase (iNOS) 
      were significantly reduced. In contrast, the M2 markers such as IL-10, IL-4, 
      CD206 and Arg1 were markedly increased by co-culturing with MSCs. Specifically, 
      the ratio of iNOS to Arg1 in BMDMs was notably downregulated by co-culturing with 
      MSCs. These results suggest that the preferential shift of the macrophage 
      phenotype from M1 to M2 may be related to the immune-modulating characteristics 
      of MSCs that contribute to cardiac repair.
FAU - Cho, Dong-Im
AU  - Cho DI
AD  - Research Laboratory of Cardiovascular Regeneration, Chonnam National University 
      Hospital, Gwangju, South Korea.
FAU - Kim, Mi Ra
AU  - Kim MR
AD  - Research Laboratory of Cardiovascular Regeneration, Chonnam National University 
      Hospital, Gwangju, South Korea.
FAU - Jeong, Hye-yun
AU  - Jeong HY
AD  - Research Laboratory of Cardiovascular Regeneration, Chonnam National University 
      Hospital, Gwangju, South Korea.
FAU - Jeong, Hae Chang
AU  - Jeong HC
AD  - Department of Cardiology, Chonnam National University Hospital, Gwangju, South 
      Korea.
FAU - Jeong, Myung Ho
AU  - Jeong MH
AD  - 1] Department of Cardiology, Chonnam National University Hospital, Gwangju, South 
      Korea [2] Heart Research Center, Chonnam National University Hospital, Gwangju, 
      South Korea.
FAU - Yoon, Sung Ho
AU  - Yoon SH
AD  - Department of Internal Medicine, School of Medicine, Chosun University, Gwangju, 
      South Korea.
FAU - Kim, Yong Sook
AU  - Kim YS
AD  - 1] Research Laboratory of Cardiovascular Regeneration, Chonnam National 
      University Hospital, Gwangju, South Korea [2] Heart Research Center, Chonnam 
      National University Hospital, Gwangju, South Korea.
FAU - Ahn, Youngkeun
AU  - Ahn Y
AD  - 1] Department of Cardiology, Chonnam National University Hospital, Gwangju, South 
      Korea [2] Heart Research Center, Chonnam National University Hospital, Gwangju, 
      South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140110
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Biomarkers)
RN  - 0 (Culture Media, Conditioned)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Biomarkers/metabolism
MH  - *Cell Differentiation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Culture Media, Conditioned/pharmacology
MH  - Humans
MH  - *Macrophage Activation
MH  - Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Macrophages/drug effects/*immunology/metabolism
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Myocardial Infarction/surgery
MH  - Rats
PMC - PMC3909888
EDAT- 2014/01/11 06:00
MHDA- 2014/09/26 06:00
PMCR- 2014/01/01
CRDT- 2014/01/11 06:00
PHST- 2013/07/01 00:00 [received]
PHST- 2013/08/20 00:00 [revised]
PHST- 2013/09/12 00:00 [accepted]
PHST- 2014/01/11 06:00 [entrez]
PHST- 2014/01/11 06:00 [pubmed]
PHST- 2014/09/26 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - emm2013135 [pii]
AID - 10.1038/emm.2013.135 [doi]
PST - epublish
SO  - Exp Mol Med. 2014 Jan 10;46(1):e70. doi: 10.1038/emm.2013.135.