Therapeutic Effects of 3D-Cultured Mesenchymal Stem Cells in Hyaluronic Acid Hydrogel on Acute Myocardial Infarction in Mice

ZHU Ying; ZHANG Yan; HAO Lu; CHEN Yu; ZHANG Ningkun

doi:10.3639/j.issn.2095-3097.2025.10.027

Abstract：Objective To study the advantages of hyaluronic acid hydrogel-based 3D culture of mesenchymal stem cell(MSC)compared to traditional 2D culture,and to evaluate its therapeutic effects in a mouse model of acute myocardial infarction(AMI),as well as to explore its underlying therapeutic mechanisms.Methods MSCs were cultured in hyaluronic acid hydrogel under 3D conditions and compared with 2D-cultured cells in terms of cell morphology,cell proliferation(MTT assay),and VEGF expression level detected by ELISA.An AMI model was established by rapid ligation of the left anterior descending coronary artery in male BALB/c mice.Twenty healthy male BALB/c mice were randomly divided into four groups(n=5 per group):sham group,phosphate-buffered saline group,2D MSCs transplantation group,and 3D MSCs transplantation group.The myocardial infarction area was measured using TTC staining and Image J software;cardiac fibrosis was assessed by HE staining,and cardiac function was evaluated by echocardiography.Results Compared with 2D-cultured cells,the 3D-cultured cells in hyaluronic acid hydrogel exhibited a more three-dimensional morphology,faster proliferation,and higher VEGF expression(P<0.01).In the AMI mouse model,the 3D MSCs transplantation group showed significantly reduced cardiac fibrosis and inflammatory cell infiltration,smaller myocardial infarction area,and largely restored cardiac function parameters by echocardiography,outperforming the 2D MSCs transplantation group(P<0.001).Conclusion Compared with 2D-cultured MSCs,3D-cultured MSCs demonstrate significant advantages in multiple aspects and exhibit better therapeutic effects on AMI,suggesting a promising new direction for cell transplantation therapy.