Korn A1,2, Simsek S3,4, Fiet MD1,2, Waas ISE5, Niessen HWM1,2,6, Krijnen PAJ1,2
1Department of Pathology, Amsterdam University Medical Centre (AUMC) Location VUmc, Amsterdam. 2Amsterdam Cardiovascular Sciences, Amsterdam. 3Department of Internal Medicine, Northwest Clinics, Alkmaar. 4Department of Internal Medicine, AUMC Location VUmc, Amsterdam. 5Department of Pathology, AUMC Location VUmc, Amsterdam. 6Department of Cardiac Surgery, AUMC Location VUmc, Amsterdam.
Email: a.korn@amsterdamumc.nl
Background: Diabetes mellitus (DM) induces increased inflammation of atherosclerotic plaques, resulting in elevated plaque instability. Mesenchymal stem cell (MSC) therapy was shown to decrease plaque size and increase stability in non-DM animal models. We now studied the effect of MSC therapy in a streptozotocin-induced hyperglycaemia mouse model using a clinically relevant dose of adipose tissue-derived MSCs (ASCs).
Method: Hyperglycaemia was induced in male C57BL/6 ApoE-/- mice (n=24) via intraperitoneal streptozotocin (STZ) injection (0.05 mg/g bodyweight) for 5 consecutive days. 16 weeks after the first STZ injection, the mice received either 100,000 ASCs (n=9) or vehicle (n=14) intravenously. The effects of ASC treatment on the size and stability of aortic root atherosclerotic plaques were determined 4 weeks post-treatment via (immuno)histochemical analyses. Furthermore, plasma monocyte subsets within 3 days pre- and 3 days post-treatment, and 4 weeks post-treatment, were studied.
Results: ASC treatment did not significantly affect atherosclerotic plaque size or intra-plaque inflammation. Although ASC-treated mice had a higher percentage of intra-plaque fibrosis (42.5±3.3%) compared to vehicle-treated mice (37.6±6.8%, p=0.07), this did not reach significance. Additionally, although differences in the percentages of circulating pro- and anti-inflammatory monocytes were observed after ASC treatment compared to pre-treatment (p=0.005), their levels did not differ significantly at any time point compared to vehicle-treated mice.
Conclusions: ASC treatment with a clinically relevant dose did not significantly affect atherosclerotic plaque size or intra-plaque inflammation in a hyperglycaemia mouse model. Despite a borderline significant improvement in intraplaque fibrotic content, the potential of ASC treatment on atherosclerotic plaque stability in a diabetic environment remains to be determined.