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Table 2 Experimental validation of ETV2 function in therapeutic angiogenesis

From: ETV2/ER71, the key factor leading the paths to vascular regeneration and angiogenic reprogramming

Animal model

Animal species

Delivery methods

Administration route and dose

Observation time points

Outcome

References

Hindlimb ischemia

Athymic nude mice

Lentivirus

Single IM injection of 25 µl (IFU 3 × 107/ml) into the adductor muscle (4 sites, a total 100 µl per animal)

Day 7, 21, 28

Improved blood perfusion

Ref. [58]

Myocardial infarct

C57/BL6

Lentivirus

Single intra-myocardial injection of 5.6 × 106 IFU per site, a total two sites

8 weeks after MI

Improved cardiac function Increased capillary density

Ref. [59]

Myocardial infarct

Fisher 344 rats

Adeno-associated virus

Single intra-myocardial injection of 1 × 1012 GC per site, two sites

8 weeks after MI

Improved cardiac function Less fibrosis

Ref. [59]

Stroke

C57/BL6

Nanochannel electroporation of plasmid DNA encoding EFF (Etv2, Foxc2, Fli1) into MEFs

Single intracranial (subarachnoid space) injection of EFF-transfected MEFs at day 7 of MCAO

Day 21 after MCAO

Enhanced cerebral vascularity, infarct resolution and motor activity

Ref. [112]

Syngenic tumor model

C57/BL6

ETV2 siRNA nanoparticle

Repeated IV injection of 1 nmol per mouse at day 9–17 after SC transplantation of LLC, a total 5 times, EOD

Day 19 after LLC transplantation

Reduction in tumor size, less vessels

Ref. [61]

Heterotopic human GBM tumor

NOD/SCID mice

Lentiviral delivery of ETV2-specific gRNA/Cas9 into GBM cells

SC transplantation of ETV2-disrupted GBM cells (5 × 106 per mouse)

2 months after GBM transplantation

Reduction in tumor size and hCD31+/KI67+ TDECs

Ref. [62]

  1. EFF Etv2/Foxc2/Fli1; EOD Every other day; GBM Glioblastoma; GC Genome copy; gRNA Guide RNA; IFU Infectious unit; IM Intramuscular; IV Intravascular; LLC Lewis lung carcinoma; MCAO Middle cerebral artery occlusion; MEFs Mouse embryonic fibroblasts; MI Myocardial infarct; NOD/SCID Non-obese diabetic/severe combined immune deficiency; SC Subcutaneous