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Sci Rep. 2015 Jun 3;5:10902. doi: 10.1038/srep10902.

Extracellular Matrix can Recover the Downregulation of Adhesion Molecules after Cell Detachment and Enhance Endothelial Cell Engraftment.

Author information

1
1] Collaborative Innovation Center for Biotherapy, Nankai University School of Medicine, Tianjin, China [2] Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, China [3] The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
2
1] Collaborative Innovation Center for Biotherapy, Nankai University School of Medicine, Tianjin, China [2] Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, China.
3
Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China.
4
1] Collaborative Innovation Center for Biotherapy, Nankai University School of Medicine, Tianjin, China [2] State Key Lab of Experimental Hematology, Chinese Academy of Medical Sciences, Tianjin, China.
5
1] Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, China [2] The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
6
State Key Lab of Experimental Hematology, Chinese Academy of Medical Sciences, Tianjin, China.
7
The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
8
Department of Radiology and Molecular Imaging Program at Stanford (MIPS).
9
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
10
Department of Cardiac Nuclear Imaging, Fuwai Hospital, Peking Union Medical College &Chinese Academy of Medical Sciences, Beijing, China.

Abstract

The low cell engraftment after transplantation limits the successful application of stem cell therapy and the exact pathway leading to acute donor cell death following transplantation is still unknown. Here we investigated if processes involved in cell preparation could initiate downregulation of adhesion-related survival signals, and further affect cell engraftment after transplantation. Human embryonic stem cell-derived endothelial cells (hESC-ECs) were suspended in PBS or Matrigel and kept at 4 °C. Quantitative RT-PCR analysis was used to test the adhesion and apoptosis genes' expression of hESC-ECs. We demonstrated that cell detachment can cause downregulation of cell adhesion and extracellular matrix (ECM) molecules, but no obvious cell anoikis, a form of apoptosis after cell detachment, was observed. The downregulation of adhesion and ECM molecules could be regained in the presence of Matrigel. Finally, we transplanted hESC-ECs into a mouse myocardial ischemia model. When transplanted with Matrigel, the long-term engraftment of hESC-ECs was increased through promoting angiogenesis and inhibiting apoptosis, and this was confirmed by bioluminescence imaging. In conclusion, ECM could rescue the functional genes expression after cell detached from culture dish, and this finding highlights the importance of increasing stem cell engraftment by mimicking stem cell niches through ECM application.

PMID:
26039874
PMCID:
PMC4454140
DOI:
10.1038/srep10902
[Indexed for MEDLINE]
Free PMC Article

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