Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration
Abstract
:1. Cardiac Wound Healing and the Road to Xenogeneic Cell Therapy
2. Overcoming the Immunological Barrier and Graft Rejection
2.1. Multilayered Immunological Challenges
2.2. Genetic Engineering to Overcome the Barriers
3. Infection Risks in Xenogeneic Cell Therapy
4. Stem Cells and Their Applications in Cardiovascular Regeneration
4.1. Porcine Mesenchymal Stem Cells as a Promising Candidate in Cardiac Regeneration
4.2. Delivery and Final Fate
4.3. Genetic Engineering to Improve Efficiency of Mesenchymal Stem Cells
5. Future Prospects for Xenogeneic Cell Therapy
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ANG-1 | angiopoietin 1 |
ATMSC | adipose tissue-derived mesenchymal stem cell |
ATSC | adipose tissue-derived stem cell |
CDC | cardiosphere-derived cells |
CRISPR | clustered regularly interspaced short palindromic repeat |
ECM | extracellular matrix |
ERK1/2 | extracellular signal-regulated kinase 1/2 |
ESC | embryonal stem cell |
FGFβ | fibroblast growth factor β |
G-CSF | granulocyte colony-stimulating factor |
GTKO | galactosyltransferase knockout |
HEV | hepatitis E virus |
HGF | hepatocyte growth factor |
HLA | human leukocyte antigen |
IGF-1 | Insulin-like growth factor 1 |
IL-8 | interleukin-8 |
iPSCs | induced pluripotent stem cells |
MHC | major histocompatibility complex |
MI | myocardial infarction |
MSC | mesenchymal stromal cells |
PCMV | porcine cytomegalovirus |
PCV | porcine circovirus |
PDGF | platelet-derived growth factor |
PD-L1 | programmed cell death ligand 1 |
PERV | porcine endogenous retroviruses |
PI3K | phosphoinositide 3-kinase |
ROS | reactive oxygen species |
SDF-1 | stromal cell-derived factor 1 |
SLA | swine leukocyte antigen |
TALEN | transcription activator-like effector nucleases |
TGFβ | transforming growth factor β |
TKO | triple knockout |
TLR4 | toll-like receptor 4 |
VEGF | vascular endothelial growth factor |
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Cell Type and Cell Number | Delivery Method | Clinical Condition | Main Outcome | Study |
---|---|---|---|---|
Autologous MSC 3 × 107 cells | Direct left ventricular injection | Acute MI | Improved cardiac function Reduced oxidative stress and inflammatory response | [114] |
Allogeneic ATMSCs 1 × 107 cells | Intracoronary infusion | Acute MI | Unaltered cardiac function Unaltered scar size Promoted revascularization | [115] |
Allogeneic ATMSCs 5 × 107 cells Overexpressing IGF-1 or HGF | Intramyocardial injection | Acute MI | Unaltered cardiac function Promoted revascularization Reduced inflammation Enhanced fibrosis | [116] |
Allogeneic ATDPCs 1.75 × 106 cells | Recellularized myocardial scaffold | Acute MI | Improved cardiac function Reduced infarct size Promoted revascularization Attenuated fibrosis | [117] |
Xenogeneic MSCs 1 × 106 cells | Intramyocardial injection | Acute MI | Improved cardiac function Unaltered infarct size Improved preservation of capillarity | [99] |
Allogeneic MSCs 1.4 × 107 cells | Intramyocardial injection | Subacute MI | Unaltered cardiac function Reduced scar size | [118] |
Autologous BMCs eNOS-transfected 1 × 107 cells | Intramyocardial injection | Subacute MI | Improved cardiac function Unaltered scar size Unaltered fibrosis | [119] |
ATSCs 1 × 107 cells | Intramyocardial injection | Subacute MI | Improved cardiac function Reduced infarct size | [120] |
Autologous MSC 6 × 107 cells | Intramyocardial injection | Chronic MI | Unaltered cardiac function Unaltered scar size Attenuation of LV wall thinning | [121] |
Autologous BMCs 5 × 106 | Left or right coronary artery infusion | Chronic MI | Improved cardiac function Promoted revascularization | [122] |
Allogeneic MSC 2 × 108 cells | Intramyocardial injection | Chronic MI | Improved cardiac function Reduced scar size | [104] |
Allogeneic MSC 1.5 × 107 cells | Recellularized collagen scaffold | Chronic MI | Improved cardiac function Reduced scar size Promoted revascularization | [123] |
Allogeneic MSCs and CDCs 3.5 × 107 cells | Intracoronary infusion | Chronic ischemic cardiomyopathy (coronary stenosis) | Improved cardiac function Unaltered perfusion Improved remote wall thickening | [124] |
Allogeneic MSCs and CSCs 2 × 108 cells | Transendocardial injection | Chronic ischemic cardiomyopathy | Improved cardiac function Reduced scar size Low-grade inflammatory infiltrates | [107] |
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Galow, A.-M.; Goldammer, T.; Hoeflich, A. Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration. Int. J. Mol. Sci. 2020, 21, 9686. https://doi.org/10.3390/ijms21249686
Galow A-M, Goldammer T, Hoeflich A. Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration. International Journal of Molecular Sciences. 2020; 21(24):9686. https://doi.org/10.3390/ijms21249686
Chicago/Turabian StyleGalow, Anne-Marie, Tom Goldammer, and Andreas Hoeflich. 2020. "Xenogeneic and Stem Cell-Based Therapy for Cardiovascular Diseases: Genetic Engineering of Porcine Cells and Their Applications in Heart Regeneration" International Journal of Molecular Sciences 21, no. 24: 9686. https://doi.org/10.3390/ijms21249686