Superselective endovascular tissue access using trans-vessel wall technique: feasibility study for treatment applications in heart, pancreas and kidney in swine.

OBJECTIVES: With the emergence of targeted cell transplantation and gene therapy, there is a need for minimally invasive tissue access to facilitate delivery of therapeutic substrate. The objective of this study was to demonstrate the suitability of an endovascular device which is able to directly access tissue and deliver therapeutic agent to the heart, kidney and pancreas without need to seal the penetration site. METHODS: In vivo experiments were performed in 30 swine, including subgroups with follow-up to evaluate complications. The previously described trans-vessel wall (VW) device was modified to be sharper and not require tip detachment to seal the VW. Injections into targets in the heart (n = 13, 24-h follow-up n = 5, 72-h follow-up n = 3), kidney (n = 8, 14-day follow-up n = 3) and pancreas (n = 5) were performed. Some animals were used for multiple organ injections. Follow-up consisted of clinical monitoring, angiography and necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney and pancreas) were used. Injections were targeted towards the subepicardium, endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex. RESULTS: Injections were successful in target organs, visualized by intraparenchymal contrast on fluoroscopy and by necropsy. No serious complications (defined as heart failure or persistent arrhythmia, haemorrhage requiring treatment or acute kidney injury) were encountered over a total of 157 injections. CONCLUSIONS: The trans-VW device can achieve superselective injections to the heart, pancreas and kidney for delivery of therapeutic substances without tip detachment. All parts of these organs including the subepicardium, pancreas tail and renal subcapsular space can be efficiently reached.

Superselective intra-arterial umbilical cord blood administration to BM in experimental animals.

Umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by the low number of cells and delayed engraftment. UCB cells are infused i.v. for transplantation, although only a proportion of the cells reach the BM. We investigated whether UCB could be administered safely using superselective intra-arterial (i.a.) injection. We injected human UCB (5 × 10(6)) into the aorta in rats, into the iliac artery in mice and into the femoral nutrient artery (FNA) in rabbits. We used angiography, immunohistochemistry, intravital microscopy and qPCR to assess safety end points and the distribution of injected cells. All animals showed normal behavior. No evidence of organ infarction was noted. UCB injected into the FNA of rabbits did not change the flow rates, measured by angiography. By qPCR, we found significantly higher fold-change values in the injected BM compared with i.v. injection (P=0.0087). Using intravital microscopy we visualized the mouse capillary bed during i.a. injection without cellular congestion. In summary, we show that i.a. infusion of UCB is safe and reaches an eightfold increase in engraftment in the BM compared with i.v. infusion. These studies lay the foundation for clinical trials.