PMID- 28651946
OWN - NLM
STAT- MEDLINE
DCOM- 20190805
LR  - 20190805
IS  - 1097-685X (Electronic)
IS  - 0022-5223 (Print)
IS  - 0022-5223 (Linking)
VI  - 154
IP  - 3
DP  - 2017 Sep
TI  - Layered smooth muscle cell-endothelial progenitor cell sheets derived from the 
      bone marrow augment postinfarction ventricular function.
PG  - 955-963
LID - S0022-5223(17)31104-2 [pii]
LID - 10.1016/j.jtcvs.2017.04.081 [doi]
AB  - OBJECTIVE: The angiogenic potential of endothelial progenitor cells (EPCs) may be 
      limited by the absence of their natural biologic foundation, namely smooth muscle 
      pericytes. We hypothesized that joint delivery of EPCs and smooth muscle cells 
      (SMCs) in a novel, totally bone marrow-derived cell sheet will mimic the native 
      architecture of a mature blood vessel and act as an angiogenic construct to limit 
      post infarction ventricular remodeling. METHODS: Primary EPCs and mesenchymal 
      stem cells were isolated from bone marrow of Wistar rats. Mesenchymal stem cells 
      were transdifferentiated into SMCs by culture on fibronectin-coated culture 
      dishes. Confluent SMCs topped with confluent EPCs were detached from an Upcell 
      dish to create a SMC-EPC bi-level cell sheet. A rodent model of ischemic 
      cardiomyopathy was then created by ligating the left anterior descending artery. 
      Rats were randomized into 3 groups: cell sheet transplantation (n = 9), no 
      treatment (n = 12), or sham surgery control (n = 7). RESULTS: Four weeks 
      postinfarction, mature vessel density tended to increase in cell sheet-treated 
      animals compared with controls. Cell sheet therapy significantly attenuated the 
      extent of cardiac fibrosis compared with that of the untreated group (untreated 
      vs cell sheet, 198 degrees [interquartile range (IQR), 151-246 degrees] vs 103 
      degrees [IQR, 92-113 degrees], P = .04). Furthermore, EPC-SMC cell sheet 
      transplantation attenuated myocardial dysfunction, as evidenced by an increase in 
      left ventricular ejection fraction (untreated vs cell sheet vs sham, 33.5% [IQR, 
      27.8%-35.7%] vs 45.9% [IQR, 43.6%-48.4%] vs 59.3% [IQR, 58.8%-63.5%], P = .001) 
      and decreases in left ventricular dimensions. CONCLUSIONS: The bone 
      marrow-derived, spatially arranged SMC-EPC bi-level cell sheet is a novel, 
      multilineage cellular therapy obtained from a translationally practical source. 
      Interactions between SMCs and EPCs augment mature neovascularization, limit 
      adverse remodeling, and improve ventricular function after myocardial infarction.
CI  - Copyright (c) 2017 The American Association for Thoracic Surgery. Published by 
      Elsevier Inc. All rights reserved.
FAU - Shudo, Yasuhiro
AU  - Shudo Y
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Goldstone, Andrew B
AU  - Goldstone AB
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Cohen, Jeffrey E
AU  - Cohen JE
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Patel, Jay B
AU  - Patel JB
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Hopkins, Michael S
AU  - Hopkins MS
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Steele, Amanda N
AU  - Steele AN
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Edwards, Bryan B
AU  - Edwards BB
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Kawamura, Masashi
AU  - Kawamura M
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif.
FAU - Miyagawa, Shigeru
AU  - Miyagawa S
AD  - Department of Cardiovascular Surgery, Osaka University Graduate School of 
      Medicine, Osaka City, Japan.
FAU - Sawa, Yoshiki
AU  - Sawa Y
AD  - Department of Cardiovascular Surgery, Osaka University Graduate School of 
      Medicine, Osaka City, Japan.
FAU - Woo, Y Joseph
AU  - Woo YJ
AD  - Department of Cardiothoracic Surgery, Stanford University School of Medicine, 
      Stanford, Calif. Electronic address: joswoo@stanford.edu.
LA  - eng
GR  - R01 HL089315/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20170524
PL  - United States
TA  - J Thorac Cardiovasc Surg
JT  - The Journal of thoracic and cardiovascular surgery
JID - 0376343
CIN - J Thorac Cardiovasc Surg. 2017 Sep;154(3):951-952. PMID: 28629840
CIN - J Thorac Cardiovasc Surg. 2017 Sep;154(3):964-965. PMID: 28645824
CIN - J Thorac Cardiovasc Surg. 2017 Sep;154(3):962-963. PMID: 28651941
MH  - Animals
MH  - *Cell Transdifferentiation
MH  - Cell Transplantation/*methods
MH  - Cells, Cultured
MH  - Endothelial Progenitor Cells/*cytology
MH  - Fibrosis/therapy
MH  - Heart Ventricles/diagnostic imaging
MH  - Magnetic Resonance Imaging
MH  - Mesenchymal Stem Cells/*cytology
MH  - Myocardial Infarction/*therapy
MH  - Myocardium/pathology
MH  - Myocytes, Smooth Muscle/*transplantation
MH  - Neovascularization, Physiologic
MH  - Rats, Wistar
MH  - Stroke Volume
MH  - Ventricular Remodeling
PMC - PMC5947323
MID - NIHMS887934
OTO - NOTNLM
OT  - cell sheet
OT  - myocardial infarction
OT  - neovascularization
OT  - regeneration
OT  - stem cells
OT  - tissue engineering
COIS- Conflicts of Interest: None
EDAT- 2017/06/28 06:00
MHDA- 2019/08/06 06:00
PMCR- 2018/09/01
CRDT- 2017/06/28 06:00
PHST- 2016/05/26 00:00 [received]
PHST- 2017/04/08 00:00 [revised]
PHST- 2017/04/12 00:00 [accepted]
PHST- 2017/06/28 06:00 [pubmed]
PHST- 2019/08/06 06:00 [medline]
PHST- 2017/06/28 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - S0022-5223(17)31104-2 [pii]
AID - 10.1016/j.jtcvs.2017.04.081 [doi]
PST - ppublish
SO  - J Thorac Cardiovasc Surg. 2017 Sep;154(3):955-963. doi: 
      10.1016/j.jtcvs.2017.04.081. Epub 2017 May 24.