RETRACTED: Differentiation of human iPSCs into VSMCs and generation of VSMC-derived calcifying vascular cells

Trillhaase, Anja; Haferkamp, Undine; Rangnau, Alexandra; Märtens, Marlon; Schmidt, Beatrice; Trilck, Michaela; Seibler, Philip; Aherrahrou, Rédouane; Erdmann, Jeanette; Aherrahrou, Zouhair

doi:10.1016/j.scr.2018.07.008

Cited by 4 publications

(2 citation statements)

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“…Osteoblastic differentiation of VSMCs plays an important role in arterial calcification ( 42 ). With phenotype switching, VSMCs alternate from contractile (differentiated) phenotype to synthetic (dedifferentiated) phenotype, as well as reduced expression of differentiation marker α-SMA ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Positive Association of Leptin and Artery Calcification of Lower Extremity in Patients With Type 2 Diabetes Mellitus: A Pilot Study

et al. 2021

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ObjectiveWe aimed to explore the role and possible mechanism of leptin in lower-extremity artery calcification in patients with type 2 diabetes mellitus (T2DM).MethodsWe recruited 59 male patients with T2DM and 39 non-diabetic male participants. All participants underwent computed tomography scan of lower-extremity arteries. The calcification scores (CSs) were analyzed by standardized software. Plasma leptin level was determined by radioimmunoassay kits. Human vascular smooth muscle cells (VSMCs) calcification model was established by beta-glycerophosphate and calcium chlorideinduction. Calcium deposition and mineralization were measured by the o-cresolphthalein complexone method and Alizarin Red staining. The mRNA expression of bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and osteopontin (OPN) was determined by quantitative RT-PCR. The protein levels of BMP2, Runx2, α-smooth muscle actin (α-SMA) and (p)-Akt was determined by Western-blot analysis, and α-SMA was also measured by immunofluorescence analysis.ResultsCompared with controls, patients with T2DM showed higher median calcification score in lower-extremity artery [286.50 (IQR 83.41, 1082.00) vs 68.66 (3.41, 141.30), p<0.01]. Plasma leptin level was higher in patients with calcification score ≥300 than ≥100 (252.67 ± 98.57 vs 189.38 ± 44.19 pg/ml, p<0.05). Compared with calcification medium, intracellular calcium content was significantly increased in VSMCs treated by leptin (200, 400 and 800 ng/ml) combined with calcification medium [11.99 ± 3.63, 15.18 ± 4.55, and 24.14 ± 5.85 mg/ml, respectively, vs 7.27 ± 1.54 mg/ml, all p<0.01]. Compared with calcification medium, Alizarin Red staining showed calcium disposition was more obvious, and the mRNA level of BMP2, Runx2 and OCN was significantly increased, and immunofluorescence and Western blot analysis showed that the expression of α-SMA was downregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium, respectively. Compared with calcification medium, the protein level of BMP2 and Runx2 was upregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium. Moreover, blocking PI3K/Akt signaling pathway can decrease the protein expression of BMP2 and Runx2 in VSMCs treated by leptin (400 ng/ml) combined with calcification medium.ConclusionsLeptin promoted lower-extremity artery calcification of T2DM by upregulating the expression of BMP2 and Runx2, and regulating phenotypic switch of VSMCs via PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Positive Association of Leptin and Artery Calcification of Lower Extremity in Patients With Type 2 Diabetes Mellitus: A Pilot Study

et al. 2021

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“…We certainly observe differences in VSMC differentiation between individuals in our group, stressing the influence the investigator has on the final outcome. Other researchers have also observed different levels of SM-MHC + cells using the same protocol or have had to modify the protocol to obtain sufficient maturity in their hands (Cheung et al, 2012;He et al, 2018;Trillhaase et al, 2018;Zhang et al, 2019). These differences could be due to the use of different iPSC lines, but are likely also impacted by variation imparted by the user.…”

Section: Scale-up and Variability Issuesmentioning

confidence: 99%

Aortic “Disease-in-a-Dish”: Mechanistic Insights and Drug Development Using iPSC-Based Disease Modeling

Davaapil

Shetty

Sinha

2020

Front. Cell Dev. Biol.

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Thoracic aortic diseases, whether sporadic or due to a genetic disorder such as Marfan syndrome, lack effective medical therapies, with limited translation of treatments that are highly successful in mouse models into the clinic. Patient-derived induced pluripotent stem cells (iPSCs) offer the opportunity to establish new human models of aortic diseases. Here we review the power and potential of these systems to identify cellular and molecular mechanisms underlying disease and discuss recent advances, such as gene editing, and smooth muscle cell embryonic lineage. In particular, we discuss the practical aspects of vascular smooth muscle cell derivation and characterization, and provide our personal insights into the challenges and limitations of this approach. Future applications, such as genotype-phenotype association, drug screening, and precision medicine are discussed. We propose that iPSC-derived aortic disease models could guide future clinical trials via "clinical-trials-in-a-dish", thus paving the way for new and improved therapies for patients.

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Differential Mechanisms of Arterial and Valvular Calcification

Rogers

Aïkawa

2020

Contemporary Cardiology

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RETRACTED: Differentiation of human iPSCs into VSMCs and generation of VSMC-derived calcifying vascular cells

Cited by 4 publications

References 31 publications

Positive Association of Leptin and Artery Calcification of Lower Extremity in Patients With Type 2 Diabetes Mellitus: A Pilot Study

Positive Association of Leptin and Artery Calcification of Lower Extremity in Patients With Type 2 Diabetes Mellitus: A Pilot Study

Aortic “Disease-in-a-Dish”: Mechanistic Insights and Drug Development Using iPSC-Based Disease Modeling

Differential Mechanisms of Arterial and Valvular Calcification

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