Abstract
Background Our previous study demonstrated that intravenous administration of mesenchymal stromal cells (MSCs) significantly increased local cell engraftment and improved heart function. We sought to investigate whether HLA-G1 overexpressed MSCs could further increase local transplanted cells engraftment and improve heart function.
Methods
and Results Mice were randomized to receive intravenous administration of saline, human umbilical cord blood derived MSCs (hUCB-MSCs) 7 days prior to acute myocardial infarction (AMI), induced by ligation of the left anterior descending coronary artery. Then, intramyocardial transplantation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) was performed 30 minutes following AMI. Echocardiographic assessment was performed to assess heart function. In-vivo fluorescent imaging analysis were used to analyze cell engraftment. Flow cytometry of splenic regulatory T cells (Tregs) and natural killer (NK) cells was conducted to evaluate the immunomodulatory effect. Our result showed that systemic intravenous administration of hUCB-MSCs significantly increased systemic Tregs, decreased systemic NK cells, increased cell engraftment of intramyocardial transplanted hiPSC-CMs, culminating in improvement of heart function. Our in-vitro study showed that HLA-G1 overexpressed hUCB-MSCs modulated immune response by decreasing pro-inflammatory cytokines.
Conclusions
Systemic intravenous administration of HLA-G1 overexpressed hUCB-MSCs modulated immune response and enhanced the survival of local transplanted hiPSC-CMs to improve heart function following AMI.
Competing Interest Statement
The authors have declared no competing interest.
Nonstandard Abbreviations and Acronyms
- AMI
- Acute Myocardial Infarction
- CM
- Cardiomyocyte
- FMO
- Fluorescence Minus One
- FS
- Fractional Shortening
- FOV
- Field Of View
- HF
- Heart Failure
- HLA
- Human Leukocyte Antigen
- hiPSC
- Human Induced Pluripotent Stem Cell
- hUCB
- Human Umbilical Cord Blood
- IDO
- Indoleamine 2, 3-Dioxygenase
- IFN
- Interferon
- IL
- Interleukin
- LVEDD
- left ventricular end-diastolic dimension
- LVEF
- left ventricular ejection fraction
- VESD
- left ventricular end-systolic dimension
- MHC
- Major Histocompatibility Complex
- MSC
- Mesenchymal Stromal Cell
- MI
- Myocardial Infarction
- NK
- Natural Killer
- PBS
- Phosphate Buffered Saline
- SEM
- Standard Error of the Mean
- SMA TNF
- Smooth Muscle Antigen Tumor Necrosis Factor
- Treg
- Regulatory T cell
- TUNEL
- TdT-mediated dUTP Nick-End Labeling
- vWF
- Von Willebrand Factor
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