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Journal of Transmitted Diseases and Immunity
ISSN: 2573-0320
Page 66
Volume 4
May 10-11, 2018
Frankfurt, Germany
Immunology Research 2018
Tissue Science 2018
JOINT EVENT
2 2
n d
E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Immunology and
Evolution of Infectious Diseases
&
1 2
t h
E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Tissue Engineering and
Regenerative Medicine
R
ecent studies suggest that the epicardium plays an important
role in cardiomyogenesis during development, while it
becomes quiescent in adult heart. Thymosin beta 4 (Tβ4) has an
effect on activating the epicardium. However, effectiveness ofTβ4
administration is unsatisfactory. Therefore, this study prepared
cardiac patch and investigated efficiency of activating the
epicardium by Tβ4 released sustainedly from the cardiac patch.
Mesenchymal stem cells (MSCs) isolated from bone marrow of
rats and mice were transfected with Tβ4. Tβ4 release from the
cells was determined with an acquity ultra-performance liquid
chromatography system. For preparing of cardiac patch, the cells
transfected with Tβ4 and Flag were seeded on PLACL/collagen
membrane formulated by electrospinning. The survival and
proliferation of the cells on the nanofibers were examined after
treatment with hypoxia. In MI models of rats and Wt1
CreERT2/+,
R26
mTmG
mice, the patches were implanted on the epicardium
of the infarcted region. In rat models, differentiation of the
epicardium-derived cells (EPDCs) and the engrafted MSCs
towards cardiomyocytes and vascular cells was examined by
Wt1 immunostaining and Flag labeling. In transgenic mouse
models, the activated EPDCs expressed GFP. At four week after
implantation of the patches, cardiac function was improved
significantly, scar area in the infarcted region was reduced
obviously. EPDCs increased in subepicardium and myocardium,
and some Wt1
+
cells and GFP
+
cells expressed CD31, α-SMA or
cTnT. Moreover, c-kit
+
cells were observed in subepicardium and
myocardium, and a few of them expressed CD31, α-SMA or cTnT.
Flag labeling showed that some engrafted MSCs migrated into
subepicardium and myocardium. These results suggest that
Tβ4 released from the transfected MSCs in PLACL/collagen
nanofibrous patches may effectively attenuate left ventricular
remodeling and improve cardiac function by activating the
epicardial cells and recruiting endogenous stem cells. Our
finding provides a novel strategy for myocardial regeneration by
enhancing the endogenous regenerative mechanisms.
References:
1. Guo H D, Cui G H, Wang H J and Tan Y Z (2010)
Transplantation of marrow-derived cardiac stem cells
carried in designer self-assembling peptide nanofibers
improves cardiac function after myocardial infarction.
Biochem Bioph Res Co. 399:42–8.
2. Guo H D, Wang H J, Tan Y Z and Wu J H (2011)
Transplantation of marrow-derived cardiac stem
cells carried in fibrin improves cardiac function after
myocardial infarction. Tissue Eng Part A 17:45–58.
3. Kai D, Wang Q L, Wang H J, Prabhakaran M P, Zhang Y
Z, Tan Y Z and Ramakrishna S (2014) Stem cell loaded
nanofibrous patch promotes regeneration of infarcted
myocardium with functional improvement in rat model.
Acta Biomaterialia. 10:2727–38.
4. Wang Q L, Wang H J, Li Z H, Wang Y L, Wu X P, Tan Y
Z (2017) Mesenchymal stem cell-loaded cardiac patch
promotes epicardial activation and repair of the infarcted
myocardium. J Cell Mol Med. 21:1751–66.
Biography
Yu-zhen Tan is a Professor in Department of Anatomy, Histology and Em-
bryology at Shanghai Medical School of Fudan University. She completed
her MD at Nanjing Medical University, China and; PhD at Shinshu University
School of Medicine, Japan. In 1999, she became a Professor of Shanghai
Medical School of Fudan University. She firstly designed and synthesized
the self-assembling peptide modified with RGDSP, and investigated effects
of the peptide carrying stem cells on repairing the infracted myocardium.
She was also first to investigate effects of the PCL/gelatin nanofibrous
patch on repairing the infracted myocardium after transplantation on the
epicardium. Her research interests include “Stemcell differentiation and car-
diovascular regenerative medicine”.
yztan@shmu.edu.cnCardiac patch loading MSCs overexpressing T
β
4 promotes
repair of the infarcted myocardium by endogenous regenerative
mechanisms
Yu-zhen Tan, Qiang-li Wang, Hai-jie Wang
and
Yong-li Wang
Shanghai Medical School of Fudan University, China
Yu-zhen Tan et al., J Transm Dis Immun 2018, Volume 2
DOI: 10.21767/2573-0320-C2-006