Injectable Decellularized Extracellular Matrix Hydrogel Containing Stromal Cell-Derived Factor 1 Promotes Transplanted Cardiomyocyte Engraftment and Functional Regeneration after Myocardial Infarction.

Abstract

Transplantation of exogenous cardiomyocytes (CMs) is a hopeful method to treat myocardial infarction (MI). However, its clinical application still remains challenging due to low retention and survival rates of the transplanted cells. Herein, a stromal cell-derived factor 1 (SDF-1)-loaded injectable hydrogel based on a decellularized porcine extracellular matrix (dECM) is developed to encapsulate and deliver CMs locally to the infarct area of the heart. The soluble porcine cardiac dECM is composed of similar components such as the human cardiac ECM, which could be self-assembled into a nanofibrous hydrogel at physiological temperature to improve the retention of transplanted CMs. Furthermore, the chemokine SDF-1 could recruit endogenous cells to promote angiogenesis, mitigating the ischemic microenvironment and improving the survival of CMs. The results in vitro show that this composite hydrogel exhibits good biocompatibility, anti-apoptosis property, and chemotactic effects for mesenchymal stromal cells and endothelial cells through SDF-1-CXCR4 axis. Moreover, intramyocardial injection of this composite hydrogel to the infarcted area leads to the promotion of angiogenesis and inhibition of fibrosis, reducing the infarction size and improving the cardiac function. The combination of natural biomaterials, exogenous cells, and bioactive factors shows potential for MI treatment in the clinical application.

• Authors: Kui Wu, Yuanyuan Wang, Hong Yang, Yihuan Chen, Kunyan Lu, Yong Wu, Chunxia Liu, Haixin Zhang, Hanyu Meng, Qian Yu, Yanxia Zhang, Zhenya Shen
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 15 Issue 2 Pg. 2578-2589 (Jan 18 2023) ISSN: 1944-8252 [Electronic] United States
• PMID: 36598791 (Publication Type: Journal Article)

Chemical References

• Chemokine CXCL12
• Decellularized Extracellular Matrix
• Hydrogels

Topics

• Animals
• Humans
• Chemokine CXCL12 (chemistry, pharmacology)
• Decellularized Extracellular Matrix (chemistry, pharmacology)
• Endothelial Cells
• Extracellular Matrix
• Hydrogels (pharmacology)
• Myocardial Infarction (therapy)
• Myocytes, Cardiac (metabolism)
• Regeneration
• Swine