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Published on: September 26, 2018
StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced
Amber Korn1,2,3, Suat Simsek4,5, Mitchell D Fiet1,2,3
1Department of Pathology, Amsterdam University Medical Centres (AUMC), Location VUmc, 1081 HV Amsterdam, The Netherlands.
Aims:
Diabetes mellitus (DM) increases cardiovascular risk by inducing atherosclerotic plaque instability. StemBell therapy (i.e., adipose tissue-derived stem cells (ASCs) coupled to ultrasound-activated microbubbles) previously improved plaque stability in non-DM ApoE-/- mice. Here, we investigated the effect of StemBell therapy on atherosclerotic plaque characteristics in a streptozotocin-induced DM mouse model.
Methods:
DM was induced in male C57BL/6 ApoE-/- mice (n = 18) via intraperitoneal streptozotocin (STZ) injection (0.05 mg/g bodyweight) for 5 consecutive days. Eight weeks after the first STZ injection, the mice received either 5 × 105 StemBells or vehicle intravenously. Due to unexpected mortality, the experiment was halted and restarted in week 9 with a final reduced dose of 1.25 × 105 StemBells to avoid complications. The effect of StemBell therapy on plaque characteristics was determined 4 weeks post-treatment in five vehicle-treated and five StemBell-treated mice via (immuno)histochemical analyses. Furthermore, plasma monocyte subsets within 3 days pre- and 3 days post-treatment, and 3 weeks post-treatment, were studied via flow cytometry.
Results:
StemBell therapy did not significantly affect atherosclerotic plaque size or intra-plaque inflammation. StemBell-treated mice had less intra-plaque Ly6G+ neutrophils (0.4 ± 0.5%) and intra-plaque Mac3+ pan-macrophages (17.7 ± 3.4%), but more CD163+ anti-inflammatory M2 macrophages (p = 0.5) compared to vehicle-treated mice, although this was non-significant.
Conclusions:
StemBell therapy did not significantly affect atherosclerotic plaque size or intra-plaque inflammation in a streptozotocin-induced DM mouse model. Future research is essential to explore the potential and limitations of StemBell therapy in DM-related atherosclerosis. The higher mortality of StemBell therapy in diabetic mice compared to the previous non-diabetic mice also warrants further investigation.
