1. Academic Validation
  2. IGF-1C domain-modified hydrogel enhanced the efficacy of stem cells in the treatment of AMI

IGF-1C domain-modified hydrogel enhanced the efficacy of stem cells in the treatment of AMI

  • Stem Cell Res Ther. 2020 Mar 26;11(1):136. doi: 10.1186/s13287-020-01637-3.
Yong Yao 1 2 Liang Yang 3 Li-Feng Feng 3 Zhi-Wei Yue 1 4 Nian-Huan Zhao 5 6 Zongjin Li 7 8 9 Zuo-Xiang He 10
Affiliations

Affiliations

  • 1 Nankai University School of Medicine, Tianjin, China.
  • 2 Department of Nuclear Medicine, The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, Guangdong, China.
  • 3 Department of Pharmacology, School of Medicine, Nankai University, Tianjin, China.
  • 4 The Key Laboratory of Bioactive Materials, Ministry of Education, the College of Life Science, Nankai University, Tianjin, China.
  • 5 Department of Nuclear Medicine, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China.
  • 6 Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Huangshi, China.
  • 7 Nankai University School of Medicine, Tianjin, China. zongjinli@nankai.edu.cn.
  • 8 The Key Laboratory of Bioactive Materials, Ministry of Education, the College of Life Science, Nankai University, Tianjin, China. zongjinli@nankai.edu.cn.
  • 9 Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China. zongjinli@nankai.edu.cn.
  • 10 Department of Nuclear Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China. zuoxianghe@hotmail.com.
Abstract

Background: Due to the low survival rate of cell transplantation, stem cell has not been widely used in clinical treatment of acute myocardial infarction (AMI). In this study, we immobilized the C domain peptide of insulin-like growth factor-1 on chitosan (CS-IGF-1C) to obtain bioactive hydrogel. The purpose was to investigate whether CS-IGF-1C hydrogel incorporated with human placenta-derived mesenchymal stem cells (hP-MSCs) can boost the survival of hP-MSCs and enhance their therapeutic effects.

Methods: hP-MSCs, which continuously expressed green fluorescent protein (GFP) and firefly luciferase (Fluc), were transplanted with CS-IGF-1C hydrogel into a mouse myocardial infarction model. Cell survival was detected by bioluminescence imaging (BLI), and cardiac function was measured by echocardiogram. Real-Time PCR and histological analysis were used to explore the therapeutic mechanism of CS-IGF-1C hydrogel.

Results: CS-IGF-1C hydrogel could induce the proliferation of hP-MSCs and exert anti-apoptotic effects in vitro. The Calcine-AM/PI staining results showed that hP-MSCs seeded on CS-IGF-1C hydrogel could protect neonatal mouse ventricular cardiomyocytes (NMVCs) against oxidative stress. It was observed by BLI that CS-IGF-1C hydrogel injected into ischemic myocardium could improve the survival rate of hP-MSCs. Histology analysis indicated that co-transplantation of the CS-IGF-1C hydrogel and hP-MSCs could increase angiogenesis, reduce collagen deposition, ameliorate left ventricular expanded, and further promote the recovery of cardiac function. Besides, we found that the inflammatory response was inhibited and the expression of apoptosis-related genes was downregulated by CS-IGF-1C hydrogel.

Conclusions: CS-IGF-1C hydrogel provides a conducive microenvironment for cells and significantly boosts the survival of hP-MSCs in mouse myocardial infarction model, which suggest that it may be a potential candidate for prolonging the therapeutic effect of hP-MSCs during AMI.

Keywords

Acute myocardial infarction; Angiogenesis; Bioluminescence imaging; CS-IGF-1C hydrogel; Human placenta–derived mesenchymal stem cells.

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