Delivery of mesenchymal stromal cell therapy via renal intra-arterial infusion

A. Keller, B.K. Møller, J.M. Sierra Parraga, C. Andersen, A. Munk, S. Lohmann, C. Moers, C.C. Baan, R.J. Ploeg, M.J. Hoogduijn, B. Jespersen, M. Eijken

Wednesday 13 march 2019

14:12 - 14:14h at Koningin Máximazaal

Categories: Basaal, Parallelsessie

Parallel session: Parallelsessie III - Basaal I

Background: Mesenchymal stromal cell (MSC) therapy has been proposed to treat kidney disease due to their immunoregulatory and regenerative capacities. Intravenous MSC infusion has been associated with off-target engraftment and intra-arterial (IA) delivery could offer a more targeted therapy. Limited knowledge is available regarding the fate and state of MSC after IA infusion. Therefore, we have studied the efficacy of this delivery route.

Methods: MSC were isolated from adipose tissue or male pigs. A female porcine unilateral kidney ischemia-reperfusion model was infused with 10 million fluorescently labeled MSC via the renal artery. 

Analysis of blood and or dissociated kidney tissue biopsies by flow cytometry allowed MSC detection. Confocal microscopy analysis of kidney biopsies allowed to identify structures where MSC are retained. 

Y-chromosome PCR allowed identification or MSC 2 weeks after infusion. 

To elucidate an active or passive mechanism for MSC retention, metabolically inactive MSC were infused and retention was analyzed.

Results: After infusion, low numbers or MSC left the kidney through the renal vein. No MSC were seen in systemic arterial blood. MSC were found in kidney tissue, predominantly in the renal cortex with 80% of MSC alive. Also, MSC were detected in kidney tissue using confocal microcopy 8h after infusion.

Heat-inactivated MSC (HI-MSC) were found in MSC. In vitro,regular MSC but not HI-MSC exhibited adherent capacities, suggesting retention was a passive process in the kidney.

Survival after 2 weeks was analyzed by Y chromosome PCR. A reduced but significant percentage of MSC was still detected in kidney tissue, while HI-MSC derived DNA was undetectable.

Conclusions: Summarizing, delivery of MSC therapy through the renal artery is feasible and effective. MSC stay in kidney tissue for 8h with a high survival rate. After 2 weeks, MSC are still found in kidney tissue. Our results suggest that MSC are retained in the kidney through a passive process but the specific interactions remain unclear and require further investigation.