Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Karyotyping and Cell Proliferation Studies
2.3. Flow Cytometry
2.4. Cardiac In Vitro Differentiation of pCPC
2.5. Quantitative Real-Time PCR
2.6. RNA-Seq Analysis
2.7. pCPC Ientiviral Transduction In Vitro
2.8. Western Blot
2.9. Immunofluorescence
2.10. Co-Culture of Engineered pCPC in Decellularized Rat Cardiac Scaffolds
2.11. Transplantation of Engineered pCPC in Swine Myocardial Infarct Model
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- Group 1: Treatment group, received subpopulations A + C = pCPC-HGF-mCherry + pCPC-IGF1-eGFP (20 × 106 cells each subpopulation/animal at 2 × 106 cells/mL, total volume 20 mL).
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- Group 2: Control group, received subpopulations B + D = pCPC-mCherry + pCPC-eGFP (20 × 106 cells each subpopulation/animal at 2 × 106 cells/mL, total volume 20 mL).
2.12. Statistical Analysis
3. Results
3.1. Characterization of Adult pCPC
3.2. Generation and Characterization of pCPC with Forced IGF-1 or HGF Overexpression
3.3. Evaluation of the Potential Effect of IGF-1 and HGF Overexpression on pCPC Gene Expression Profile
3.4. IGF-1 Synergizes with Decellularized Rat Cardiac Scaffolds in the Promotion of Cardiogenic Differentiation of pCPC
3.5. In Vivo Evaluation of pCPC-IGF1-eGFP and pCPC-HGF-mCherry Co-Administration for the Treatment of Swine Myocardial Infarct
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Protein | Description | Others | Type | Log FC pCPC/hCPC | RU pCPC |
---|---|---|---|---|---|
Membrane | |||||
F11R | Junctional adhesion molecule A | CD321/JAM1 | Int M | 2.45 | 16.3 |
IL1R1 | Interleukin 1 receptor, type I | IL-1R-alpha | TK-R | 1.07 | 182 |
IGF2R | IGF Cation-independent mannose-6-phosphate receptor | CD222/M6P-R | Mb-R | 0.31 | 16.1 |
DPP4 | Dipeptidyl peptidase 4 | CD26 | Int M Gly | −0.38 | 190.2 |
CACNG7 | Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 7 | TARP Gamma-7 | TM | −0.98 | 42.5 |
ECE1 | Endothelin-Converting Enzyme 1 | ECE | Enz | −1.6 | 157 |
GPR4 | G Protein-Coupled Receptor 4 | G-PCR 19 | TM | −7.74 | 0.21 |
Secretome | |||||
IL1B | Interleukin 1 Beta | IL-1 Beta | Cyt | 9.1 | 100.4 |
IGF1 | Insulin-Like Growth Factor 1 | - | GF | 8.77 | 55 |
IL1A | Interleukin 1 Alpha | Hematopoietin-1 | Cyt | −1.81 | 122 |
TGF b1 | Transforming Growth Factor Beta 1 | TGF-Beta-1 | GF | −2.76 | 1565 |
Cytoplasm | |||||
PAPSS2 | 3′-Phosphoadenosine 5′-Phosphosulfate Synthase 2 | Adeno 5-Phosphosulfate Kinase | kin | 2.77 | 1889 |
P4HA1 | Prolyl 4-Hydroxylase Subunit Alpha 1 | P4HA | Hydrox | 1.22 | 1423 |
PHD1 | Prolyl Hydroxylase Domain-Containing Protein 1 | EGLN2 | Hydrox | −0.42 | 81.2 |
Nuclear | |||||
IGF2BP2 | Insulin-Like Growth Factor 2 MRNA Binding Protein 2 | IMP2 | RNA-BP | 0.05 | 175.8 |
IGF2BP3 | IGF2 MRNA-Binding Protein 3 | IMP3 | RNA-BP | 0.42 | 71.4 |
GATA4 | GATA Binding Protein 4 | - | TF | −0.3 | 44 |
WT1 | Wilms Tumor 1 | WR33 | TF | −0.91 | 6.29 |
Groups | Group 1 (Treatment, n = 9) | Group 2 (Control, n = 7) | ||
---|---|---|---|---|
1 Week (Preinjection) | 10 Weeks | 1 Week (Preinjection) | 10 Weeks | |
LVEF (%) | 28 ± 5 | 26 ± 12 | 23 ± 7 | 19 ± 5 |
LVEDVi (mL/m2) | 93 ± 15 | 106 ± 41 | 113 ± 20 | 122 ± 25 |
LVESVi (mL/m2) | 67 ± 15 | 82 ± 42 | 86 ± 18 | 99 ± 26 |
Infarct Size (%) | 20 ± 4 | 14 ± 3 | 24 ± 4 | 15 ± 4 |
Δ LVEF (%) | n/a | −2.2 ± 10 | n/a | −3.7 ± 6.9 |
Δ LVEDVi (mL/m2) | n/a | 12.8 ± 31 | n/a | 9 ± 22.8 |
Δ LVESVi (mL/m2) | n/a | 15.2 ± 30 | n/a | 12.2 ± 21.2 |
Δ Infarct Size (%) | n/a | −6.7 ± 3.3 | n/a | −9.7 ± 5.8 |
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Prat-Vidal, C.; Crisóstomo, V.; Moscoso, I.; Báez-Díaz, C.; Blanco-Blázquez, V.; Gómez-Mauricio, G.; Albericio, G.; Aguilar, S.; Fernández-Santos, M.-E.; Fernández-Avilés, F.; et al. Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction. Cells 2021, 10, 2571. https://doi.org/10.3390/cells10102571
Prat-Vidal C, Crisóstomo V, Moscoso I, Báez-Díaz C, Blanco-Blázquez V, Gómez-Mauricio G, Albericio G, Aguilar S, Fernández-Santos M-E, Fernández-Avilés F, et al. Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction. Cells. 2021; 10(10):2571. https://doi.org/10.3390/cells10102571
Chicago/Turabian StylePrat-Vidal, Cristina, Verónica Crisóstomo, Isabel Moscoso, Claudia Báez-Díaz, Virginia Blanco-Blázquez, Guadalupe Gómez-Mauricio, Guillermo Albericio, Susana Aguilar, María-Eugenia Fernández-Santos, Francisco Fernández-Avilés, and et al. 2021. "Intracoronary Delivery of Porcine Cardiac Progenitor Cells Overexpressing IGF-1 and HGF in a Pig Model of Sub-Acute Myocardial Infarction" Cells 10, no. 10: 2571. https://doi.org/10.3390/cells10102571