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Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Endogenous bone-marrow-derived stem cells contribute only a small proportion of regenerated myocardium in the acute
Shinya Fukuhara1, Shinji Tomita, Takeshi Nakatani
1Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, 565-8565, Japan.
Insights
Granulocyte-colony stimulating factor (G-CSF) promotes bone marrow cells (BMC) to regenerate heart tissue after infarction. However, bone marrow-derived cells contribute minimally to myocardial regeneration compared to non-bone marrow sources.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Stem Cell Biology
Background:
- Granulocyte-colony stimulating factor (G-CSF) facilitates bone marrow cell (BMC) migration to infarcted hearts.
- Previous studies indicated BMCs differentiate into cardiomyocytes, but their contribution to myocardial regeneration remains unclear.
Purpose of the Study:
- To quantify the proportional contribution of bone marrow (BM) and non-bone marrow (n-BM) cells to neomyocardium regeneration post-myocardial infarction.
- To assess the role of G-CSF in mobilizing BMCs for cardiac repair.
Main Methods:
- Irradiated mice received green fluorescent protein (GFP)-labeled BMCs.
- Myocardial infarction was induced via coronary artery ligation.
- G-CSF was administered, and heart tissues were analyzed for BM-derived cell contribution using histology and cell markers (troponin I, nestin, Ki67).
Main Results:
- The chimeric rate of GFP-BMC was 54.6%.
- BM-derived cells constituted a small fraction of regenerated cardiomyocytes (6.7% +/- 1.7% for troponin I-positive cells).
- Non-bone marrow sources significantly predominated in myocardial regeneration.
Conclusions:
- Bone marrow is a source of regenerated cardiomyocytes after myocardial infarction.
- The contribution of bone marrow-derived cells to myocardial regeneration is minor compared to non-bone marrow sources.
Background:
Our recent study showed that granulocyte-colony stimulating factor (G-CSF) promoted bone-marrow cells (BMC) to migrate into the infarcted heart and that they differentiated into cardiomyocytes. However, we still do not know to what degree bone-marrow-derived cardiomyocytes contribute to myocardial regeneration after injury. In this study, we verified the proportional contribution of cells from bone marrow (BM) and from non-bone marrow (n-BM) in regenerating neomyocardium after myocardial infarction.
Methods:
Eight C57BL/6 mice were irradiated (900 cGy), and green fluorescent protein (GFP) mouse-derived BMCs (GFP-BMC, 1 x 10(6) cells) were injected. Four weeks later, the left descending coronary artery was ligated. Recombinant human G-CSF (200 microg/kg/day, 8 days) was injected. At 4 weeks after ligation, hearts were fixed for histology. We calculated the proportions of cardiomyocytes derived from BM and n-BM after taking the chimeric rate into consideration.
Results:
The chimeric rate was 54.6% +/- 5.9%. At the infarcted border area, the total cell number was 1000.3 +/- 56.5/mm(2), and mobilized BM-derived GFP-BMC was 103.3 +/- 13.1/mm(2). After compensation with the chimeric rate, we found BM-derived troponin I-positive cells at 23.9 +/- 4.1/mm(2), nestin-positive cells at 12.9 +/- 2.6/mm(2), and Ki67-positive cells at 18.3 +/- 2.6/mm(2), respectively. We found significant differences in the contribution of troponin I-(6.7% +/- 1.7% vs 93.3% +/- 1.7%), nestin- (2.4 +/- 0.5 vs 97.6 +/- 0.5), and Ki67-positive (3.9 +/- 1.0 vs 96.1 +/- 1.0) cells derived from BM and n-BM.
Conclusions:
Bone marrow was one of the origins of regenerated cardiomyocytes; however, the contribution of cells from BM was very small compared with those of n-BM origin in the infarction model.
