Table 3.
Overview of the various large animal models of cardiac regeneration using growth factors, proteins, and other regenerative molecules.
| Growth Factors, Proteins, and Other Molecules | ||||
|---|---|---|---|---|
| Molecule Delivery Method |
Animal Model Sample Size Follow-Up |
Main Effects | Proposed Mechanism | |
| VEGF + angiopoietin-1 AAV mc. |
Pig (AMI) (n = 24) 8 w |
↑ LVEF ↑ Capillary density |
↑ Angiogenesis ↑ CM proliferation ↓ Apoptosis |
[58] |
| VEGF + PDGF-B AAV i.c. |
Pig (reduction stent) (n = 27) 56 d |
↑ LVEF ↑ Collateralization |
[59] | |
| VEGF-A plasmid + GET mc. |
Pig (AMI) (n = 37) 7 w |
↑ Angiogenesis | [60] | |
| VEGF-B167 AAV i.c. |
Canine (dilated CMP) (n = 53) |
↑ LVEF ↓ LVEDP ↑ dP/dtmax |
↓ Apoptosis | [61] |
| FGF-1 + CHIR99021 NPs mc. |
Pig (AMI) (n = 12) 28 d |
↑ LVEF ↑ Angiogenesis |
CM cell cycle reentry | [62] |
| Microencapsulated IGF-1 i.c. |
Pig (AMI) (n = 24) 10 w |
↑ LVEF (+18%) ↓ CVF ↓ ESVi |
↑ Angiogenesis ↓ Apoptosis |
[64] |
| rhPDGF-AB i.v. |
Pig (AMI) (n = 36) 28 d |
↑ Survival ↑ LVEF ↑ Scar anisotropy ↓ VT |
↑ Angiogenesis Fibroblast modulation |
[65] |
| TIMP-3 i.c. |
Pig (AMI) (n = 17) 28 d |
↓ Infarct size (−45%) ↓ LV dilation (−40%) |
MMP inhibition | [70] |
| rhAgrin i.c. |
Pig (AMI) (n = 19) 28 d |
↑ LVEF ↓ Scar size ↓ Adverse remodeling |
CM cell-cycle reentry ↑ Angiogenesis ↓ Inflammation |
[71] |
| Fstl-1 Epicardial patch |
Pig (AMI) (n = 6) 5 w |
↑ LVEF ↓ Scar size ↑ CM proliferation ↑ Arteriogenesis |
↑ Cardiogenesis ↓ Apoptosis |
[73] |
| AnxA1 cardiotropic AAV i.v. |
Pig (AMI) (n = 7) 7 d |
↑ VEGF-A Macrophage polarization |
Macrophage modulation | [75] |
| Ccna2 AAV mc. |
Pig (AMI) (n = 27) 6 w |
↑ LVEF ↑ CM proliferation |
CM cell-cycle reentry | [76] |
| SCF mc. |
Pig (AMI) (n = 22) 3 m |
↑ LVEF (+12%) ↑ Angiogenesis |
↑ Angiogenesis ↓ Apoptosis |
[77] |
| Tβ4 + MRTF-A AAV i.v. |
Pig (reduction stent) (n = 20) 56 d |
↑ LVEF ↓ LVEDP ↑ Collateralization |
↓ Apoptosis ↑ Collateralization |
[78] |
Main effects are always reported as (control vs. treatment); if no second value is reported, the value is the calculated relative difference between treatment and control. Only significant values are reported in the main effects column (p < 0.05). Sample size reports the total number of animals enrolled in the study. Abbreviations: NPs: nanoparticles, CVF: collagen volume fraction, ESVi: end systolic volume (indexed to Body Surface Area), VT: ventricular tachycardia.