In vivo tracking of live and dead mesenchymal stromal cells

---

S.F.H. de Witte, M. Gargesha, A.M. Merino Rodriguez, S.J. Elliman, P.N. Newsome, D. Roy, C.C. Baan, M.J. Hoogduijn

Chair(s): Prof. dr. C.C. Baan & dr. M.R. Rookmaaker

Wednesday 8 march 2017

18:42 - 18:54h at Hendrik Marsmanzaal

Categories: Parallel - Basaal

Parallel session: Parallelsessie V – Basaal 1 - Analyse niet-hematopoietische cellen in orgaantransplantatie

---

Introduction:
Mesenchymal stromal cells (MSC) are under investigation as an experimental immunomodulatory therapy. Their administration is commonly by intravenous (IV) infusion, although previous studies have reported that MSC infused by this method are trapped in the lungs and mostly disappear within a day. It is unclear what happens to MSC after their disappearance from the lungs. In the present study we examined the bio distribution and survival of MSC after IV infusion with CryoViz 3D imaging technology.

Material and Methods:
Human umbilical cord derived MSC were double-labelled with Qtracker605 beads, which are contained in live cells, and Hoechst3242, which is a DNA stain visible in live and dead cells. Labelled MSC were infused via the tail vein (120 000) into C57Bl/6 mice. To analyse the bio distribution of live and dead cells, whole body imaging of mice was performed at 5 minutes and 24 hours after MSC infusion via 3D imaging using CryoViz.

Results:
Directly after administration, the majority of MSC were alive and located in the lungs (86±11% from the total amount of cells present), with a small percentage located in the liver (2±0.5%). A small percentage of live MSC were identified in other organs at 5 min (16±9%) and 24 hours (2±1%). After 24 hours a significant decrease in the numbers of live MSC in the lungs was observed, whereas, an accumulation of dead cells was observed in the liver after 24 hours.

Discussion:
From these data we can conclude that after getting trapped in the lungs, MSC are relocated to the liver after 24 hours, although at this stage most of the MSC are dead. The biological effect of the accumulation of dead MSC in the liver is yet unknown. These findings help us further understand the fate of MSC after IV infusion, which is useful for understanding the mechanisms of MSC therapy.