Bioimaging to monitor the in vivo Distribution of administered Mesenchymal stem cells (MSCs) for treating Graft versus Host Disease (GVHD) (141.12)

Abstract

Acute Graft-versus-Host Disease (GVHD) remains a major complication after allogeneic hematopoietic cell transplantation (HCT). Several publications show a potential benefit of human MSCs for the treatment of refractory GVHD; however, their cellular fate and distribution remain unclear. We set out to develop an animal model that can be used to study the effect of MSCs on GVHD. GVHD was induced by transplantating C3H/he or C57BL/6 donor bone marrow cells (5 × 106) and CD3+ spleen cells (1 × 106) into lethally irradiated BALB/c recipient mice. C3H/10T1/2 cell lines were transfected with a pcDNA3.1-luciferase construct (luc-MSCs). Bioluminescence of these cells was measured (IVIS-Xenogen system) after treatment with luciferin, showing a linear increase of photon emission with rising cell numbers. To track these cells in vivo, groups of mice were injected with various dose luc-MSCs per animal and imaged with bioluminescence imaging at various time points. After transplantation, mice were monitored daily for weight and survival. Differences in symptom severity were compared using a clinical GVHD scoring system. We conclude that this mouse model can be used to study the effects of MSCs on acute GVHD and the described bioluminescence technology provides a sensitive and safe tool for the repeated in vivo tracking of infused luc-MSCs in GVHD target organs.