Vytaute Starkuviene’s research while affiliated with Heidelberg University and other places

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Publications (11)


ABCB5⁺ MSCs. Cultured ABCB5⁺ MSCs are shown at passage 5, grown in Ham’s F10 Medium supplemented with 10% (v/v) FBS, 1% (v/v) penicillin/streptomycin (P/S), and 1% (v/v) L-glutamine (Scale bar: 100 µm).
Immunomodulatory mechanisms of ABCB5⁺ MSCs.
Differentiation potential of ABCB5⁺ MSCs.
Summary of literature on the (potential) clinical applications of ABCB5 + MSCs.
The Differentiation and Regeneration Potential of ABCB5 Mesenchymal Stem Cells: A Review and Clinical Perspectives
  • Literature Review
  • Full-text available

January 2025

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4 Reads

Zheng He

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Vytaute Starkuviene

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Michael Keese

Mesenchymal stem cells (MSCs) are a family of multipotent stem cells that show self-renewal under proliferation, multilineage differentiation, immunomodulation, and trophic function. Thus, these cells, such as adipose tissue-derived mesenchymal stem cells (ADSCs), bone marrow-derived MSCs (BM-MSCs), and umbilical cord-derived mesenchymal stem cells (UC-MSCs), carry great promise for novel clinical treatment options. However, the challenges associated with the isolation of MSCs and the instability of their in vitro expansion remain significant barriers to their clinical application. The plasma membrane-spanning P-glycoprotein ATP-binding cassette subfamily B member 5 positive MSCs (ABCB5⁺ MSCs) derived from human skin specimens offer a distinctive advantage over other MSCs. They can be easily extracted from the dermis and expanded. In culture, ABCB5⁺ MSCs demonstrate robust innate homeostasis and a classic trilineage differentiation. Additionally, their ability to modulate the recipients’ immune system highlights their potential for allogeneic applications in regenerative medicine. In this review, we primarily discuss the differentiation potential of ABCB5⁺ MSCs and their perspectives in regenerative medicine.

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High-Content Analysis of MicroRNAs Facilitates the Development of Combinatorial Therapies for Vascular Diseases

May 2021

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78 Reads

Jian Zhang

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Vytaute Starkuviene

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[...]

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Michael Keese

In response to vascular injury vascular smooth muscle cells (VSMCs) alternate between a differentiated (contractile) and a dedifferentiated (synthetic) state or phenotype. Although parts of the signaling cascade regulating the phenotypic switch have been described, little is known on the role of miRNAs involved. To systematically address this issue, we have established a microscopy-based quantitative assay and identified 23 miRNAs that induced contractile phenotypes when over-expressed. These were then correlated to miRNAs identified from RNA-sequencing when comparing cells in the contractile and synthetic states. Using both approaches, six miRNAs (miR-132-3p, miR-138-5p, miR-141-3p, miR-145-5p, miR-150-5p, and miR-22-3p) were filtered as candidates that induce the phenotypic switch from synthetic to contractile. To identify potentially common regulatory mechanisms of these six miRNAs, their predicted targets were compared with five miRNAs sharing ZBTB20, ZNF704, and EIF4EBP2 as common potential targets and four miRNAs sharing 16 common potential targets. The interaction network consisting of these 19 targets and additional 18 hub targets were created to facilitate validation of miRNA-mRNA interactions by suggesting the most plausible pairs. Furthermore, the information on drug candidates was integrated into the network to predict novel combinatorial therapies that encompass the complexity of miRNAs-mediated regulation. This is the first study that combines phenotypic screening approach with RNA sequencing and bioinformatics to systematically identify miRNAs-mediated pathways and to identify potential drug candidates to positively influence the phenotypic switch of VSMCs.


Figure S4

December 2012

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8 Reads

Efficiency test of siRNAs targeting EGFR and TfR. Cells were transfected with the respective siRNAs and the negative control and RT-PCR was performed 48 h after the incubation. Expression of mRNA encoding GAPDH was used for the normalization. Graphs bars indicate the average values derived from 3 independent transfection experiments and error bars indicate standard errors. *, p≤0,05; (TIF)



Figure S1

December 2012

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10 Reads

Tests of Pre-miRs functionality. (A) Test of miRNAs over-expression by qRT-PCR. Cells were transfected with the corresponding Pre-miRs and negative controls and qRT-PCR was performed 48 h after the transfection with TaqMan MicroRNA assays. Y axis represents relative changes in the miRNA expression levels, expressed in a logarithmic scale. (B) Test of miRNAs over-expression by dual luciferase assay. The assay was performed 48 h after co-transfection of the reporter constructs with the complementary miRNA binding sites and the respective RNA oligonucleotides. Changes in the reporter expression level were quantified as Renilla/firefly luciferase ratio normalized against the control sample. In both graphs bars indicate the average values derived from 2–3 independent transfection experiments (for more see Materials and Methods), error bars indicate standard errors. *, p≤0,05; **, p≤0,01; ***, p≤0,001 when compared to mock-transfected cells in (A) or to cells transfected only with luciferase reporter plasmid in (B). (TIF)


Figure S5

December 2012

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10 Reads

Microscopy-based assay to quantify miRNA influence on cell proliferation. (A) Example images to demonstrate four classes of nuclei considered in the automated image analysis are represented in the upper row. Confusion matrix for classification of these phenotypes using a weighted SVM classifier with fourfold cross-validation and accuracy of the results are demonstrated in the lower row. (B) Over-expression of miR-17 seed sequence family reduces the number of mitotic cells. Cells were transfected with the respective Pre-miRs and the negative control, and the fluorescence microscopy based assay to identify mitotic cells was performed in living cells (see Methods). Bars show mean values of two independent experiments and error bars show the standard errors of the means. (C) Over-expression of the members of miR-17 seed family inhibits cell proliferation. Cells were transfected with Pre-miRs or INCENP siRNA and the total number of cells was quantified after 72 h of continues incubation. Cell numbers of the population transfected with the negative control was set to 1. *, p≤0,05; **, p≤0,01; ***, p≤0,001, (when compare to mock-transfected cells in (C)). (TIF)



Figure S3

December 2012

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12 Reads

TBC1D2 and LDLR are directly targeted by miR-17 seed family. HeLa cells were co-transfected with the reporters containing wild-type 3′UTRs of LDLR and TBC1D2 and mutated 3′UTR of TBC1D2, Pre-miR-20a, Pre-miR-93 and Pre-miR-92a. Luciferase activity was measured 24 h following the co-transfection. The activity of luciferase for each experiment was normalized to the activity of the control samples, co-transfected with the respective reporter vector and control Pre-miR (see Methods). The bars show mean fold changes of luciferase activity and the error bars show s.e.m. derived from 3 independent experiments. **, p≤0,01; ***, p≤0,001. (TIF)