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Application of Adipose Tissue-derived Stem Cell Therapy with a Clinically Relevant Dose Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-induced Hyperglycaemia Mouse Model

Overview

Overview

Journal J Mol Cell Cardiol Plus

Date 2025 Jan 13

PMID 39803590

Authors

Authors

Amber Korn

Suat Simsek

Mitchell D Fiet

Ingeborg S E Waas

Hans W M Niessen

Paul A J Krijnen

Affiliations

Affiliations

Soon will be listed here.

Abstract

Aims: 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).

Methods: Hyperglycaemia was induced in male C57BL/6 ApoE mice (=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 (=9) or vehicle (=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%, =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 (=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.

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