Journal
BIOACTIVE MATERIALS
Volume 6, Issue 12, Pages 4415-4429Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.04.010
Keywords
Stem cell-laden splenic hydrogel; hiPSC differentiation platform; Antioxidant stress; Myocardial infarction; Cardiac repair
Funding
- Key projects of the National Natural Science Foundation of China [81830055]
- National Science Fund for Distinguished Young Scholars [31625011]
- National Key Research and Development Program [2016YFC1101100]
- National Science Fund for Outstanding Young Scholars [31822021]
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Researchers developed a splenic extracellular matrix derived hydrogel to efficiently induce human pluripotent stem cells into endothelial and cardiac cells, as well as protect them from oxidative stress damage. In vivo studies showed that this hydrogel improved cardiac function and inhibited fibrosis in infarcted hearts.
Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.
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