Related Experiment Video
Updated: Aug 19, 2026
Ultrasound-Guided Induced Pluripotent Stem Cell-Derived Cardiomyocyte Implantation in Myocardial Infarcted Mice
Published on: March 30, 2022
G-CSF promotes bone marrow cells to migrate into infarcted mice heart, and differentiate into cardiomyocytes
Shinya Fukuhara1, Shinji Tomita, Takeshi Nakatani
1Department of Regenerative Medicine & Tissue Engineering, National Cardiovascular Center, Osaka, Japan. shinyafukuhara@hotmail.com
Insights
Granulocyte-colony stimulating factor (G-CSF) enhances survival and promotes bone marrow cell migration to infarcted heart tissue. This study demonstrates that bone marrow cells can differentiate into cardiomyocytes, improving cardiac function after myocardial infarction.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Stem Cell Biology
Background:
- Granulocyte-colony stimulating factor (G-CSF) has shown potential in improving cardiac function post-infarction.
- The precise mechanism, particularly the role of mobilized stem cells, remains unclear.
- Investigating stem cell origins and G-CSF efficacy is crucial for understanding cardiac repair.
Purpose of the Study:
- To investigate the origin and phenotypic changes of migrated stem cells after G-CSF treatment.
- To evaluate the therapeutic efficacy of G-CSF in a mouse model of myocardial infarction.
- To determine if bone marrow cells contribute to cardiomyocyte regeneration.
Main Methods:
- Irradiated C57BL/6 mice received GFP-mouse bone marrow cells (GFP-BMC).
- Myocardial infarction was induced via coronary artery ligation.
- Mice received either G-CSF or saline, followed by histological analysis of cardiac tissue.
Main Results:
- G-CSF treatment significantly increased survival rates post-infarction (100% vs. 50%).
- G-CSF significantly promoted the migration of bone marrow-derived GFP cells (BMD-GFP) to the infarcted border zone.
- BMD-GFP cells expressed cardiomyocyte (troponin I, myosin heavy chain-slow) and neural (nestin) markers, with increased proliferation (Ki-67).
Conclusions:
- G-CSF administration improves survival and promotes bone marrow cell homing to infarcted cardiac regions.
- Bone marrow-derived cells contribute to cardiac repair by differentiating into cardiomyocytes.
- G-CSF represents a promising therapeutic strategy for myocardial infarction by enhancing stem cell-mediated regeneration.
Abstract:
A recent study showed that granulocyte-colony stimulating factor (G-CSF) treatment improved the infarcted cardiac function. Although mobilized stem cells may affect it, the mechanism is unclear. In this study, we investigated the origins of stem cells and phenotypic changes of the migrated cells, and evaluated the efficacy of G-CSF. Eighteen C57BL/6 mice were irradiated (900 cGy) and GFP mouse-derived bone marrow cells (GFP-BMC: 10(6) cells) were injected via a tail vein followed by splenectomy 4 weeks later. Ligation of the left descending coronary artery was performed 2 weeks later. Recombinant human G-CSF (200 microg/kg/day) was injected for 3 days before and 5 days after ligation (group 1, n = 10). Saline was injected in group 2 (n = 8). Four weeks after infarction, hearts and other organs were fixed for histology. The survival rate after postoperative day 3 in group 1 was 100%, while that in group 2 was 50% (p = 0.03). Bone marrow-derived GFP cells (BMD-GFP) in group 1 (103.3+/-71.9/mm2) were located at the infarcted border area significantly more than those in group 2 (43.6+/-23.7/mm2) (p < 0.0001). BMD-GFP cells were positive for troponin I (16.6%), myosin heavy chain-slow (16.7%), and nestin (8.8%) in group 1. Ki-67-positive BMD-GFP in group 1 (10.0+/-7.0/mm2) were significantly more than those in group 2 (4.8+/-6.1/mm2) (p = 0.01). G-CSF increased the survival rate after infarction. G-CSF promoted BMC to migrate into the infarcted border area. Bone marrow was one of the origins of regenerated cardiomyocytes.
