StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced Diabetes Mellitus Mouse Model

Amber Korn; Suat Simsek; Mitchell D. Fiet; Ingeborg S.E. Waas; Klazina Kooiman; Hans W.M. Niessen; Paul A.J. Krijnen

doi:10.3390/biology14091130

StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced Diabetes Mellitus Mouse Model

Amber Korn^*
, Suat Simsek
, Mitchell D. Fiet
, Ingeborg S.E. Waas
, Klazina Kooiman
, Hans W.M. Niessen
, Paul A.J. Krijnen

^*Corresponding author for this work

Cardiology

University of Amsterdam
Amsterdam UMC
North West Hospital Group

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

31 Downloads (Pure)

Abstract

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.

Original language	English
Article number	1130
Journal	Biology
Volume	14
Issue number	9
DOIs	https://doi.org/10.3390/biology14091130
Publication status	Published - 26 Aug 2025

Bibliographical note

Publisher Copyright:
© 2025 by the authors.

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StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced Diabetes Mellitus Mouse ModelFinal published version, 2.89 MBLicence: CC BY

Cite this

@article{15704807d15f44dd8f115c38b3cf9fa0,

title = "StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced Diabetes Mellitus Mouse Model",

abstract = "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.",

author = "Amber Korn and Suat Simsek and Fiet, \{Mitchell D.\} and Waas, \{Ingeborg S.E.\} and Klazina Kooiman and Niessen, \{Hans W.M.\} and Krijnen, \{Paul A.J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 by the authors.",

year = "2025",

month = aug,

day = "26",

doi = "10.3390/biology14091130",

language = "English",

volume = "14",

journal = "Biology",

issn = "2079-7737",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

TY - JOUR

T1 - StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced Diabetes Mellitus Mouse Model

AU - Korn, Amber

AU - Simsek, Suat

AU - Fiet, Mitchell D.

AU - Waas, Ingeborg S.E.

AU - Kooiman, Klazina

AU - Niessen, Hans W.M.

AU - Krijnen, Paul A.J.

PY - 2025/8/26

Y1 - 2025/8/26

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105017381352

U2 - 10.3390/biology14091130

DO - 10.3390/biology14091130

M3 - Article

C2 - 41007277

AN - SCOPUS:105017381352

SN - 2079-7737

VL - 14

JO - Biology

JF - Biology

IS - 9

M1 - 1130

ER -

StemBell Therapy Does Not Significantly Affect Atherosclerotic Plaque Characteristics in a Streptozotocin-Induced Diabetes Mellitus Mouse Model

Abstract

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