Canine adipose-derived mesenchymal stromal cells inhibit the growth of canine hematologic malignancy cell lines

Abstract

Introduction

Intestinal lymphoma may be latent in some dogs with chronic inflammatory enteropathy. Mesenchymal stromal cells (MSCs) have potential therapeutic applications for refractory chronic inflammatory enteropathy, but their impact on the development of potential intestinal lymphomas has not yet been evaluated. Therefore, this study was performed to investigate the effect of canine adipose-derived MSCs (cADSCs) on the growth of canine lymphoma cell lines to assess the safety of MSC-based therapy in terms of pro- and anti-tumorigenic effects.

Methods

CADSCs were co-cultured with canine lymphoma/leukemia cell lines of various lineages, with or without cell-to-cell contact, to evaluate their effects on proliferation, apoptosis, and cell cycle progression in vitro. Additionally, a bioluminescent canine lymphoma cell line, established through firefly luciferase transduction, was co-injected with varying doses of cADSCs into immunocompromised mice. The growth of canine lymphoma cells was monitored over time in vivo using bioluminescence imaging.

Results

CADSCs inhibited the proliferation of all canine lymphoma/leukemia cell lines in a dose-dependent manner in vitro, under conditions allowing cell-to-cell contact. This inhibition occurred via the induction of apoptosis, G0/G1 phase cell cycle arrest, or both mechanisms. However, these effects were lost when the cells were physically separated using Transwell inserts. In xenotransplantation mouse models, cADSCs dose-dependently inhibited canine lymphoma cell growth and lung metastasis, as indicated by reduced bioluminescence signals.

Conclusions

This study has demonstrated for the first time that cADSCs inhibit the growth of different lineages of canine lymphoma/leukemia cells both in vitro and in vivo. These findings suggest that MSC-based cell therapy could potentially be applied to canine chronic inflammatory enteropathy without increasing the risk of promoting the growth of latent intestinal lymphomas.