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Kyriakides, T.

Publications and source records attributed to Kyriakides, T..

4 recordsLinked to original sources

Epithelial Reprogramming and Transition during Pulmonary Bioengineering

Recent research has emphasized the critical role of cell state transitions in tissue homeostasis. In lung biology, transitional cells are recognized as a feature of tissue-scale processes during both normal physiology and disease. The precise way that transitional cell states emerge and are regulated remains to be determined. Engineered tissues, built in a laboratory through bioengineering approaches, allow detailed study of cellular states that are not commonly found in native biology, and allow opportunities to directly induce and manipulate cellular transitions. The following study explores and characterizes epithelial cell states that emerge via cellular reprogramming in a tissue engineering context. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/701406v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1d456f3org.highwire.dtl.DTLVardef@1989ba5org.highwire.dtl.DTLVardef@127dd7org.highwire.dtl.DTLVardef@3dd7a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Curvature-Encoded Photochemistry for Programmable Isolation and Fractionation of Extracellular and Plasma Membrane Vesicles

AbstractLipid-based nanoparticles, including extracellular vesicles (EVs), cell membrane vesicles (CMVs), and biomimetic nanovesicles, are emerging as powerful carriers for therapy and diagnosis due to their ability to transport diverse payloads across biological barriers. EVs, in particular, show promise for liquid biopsy and systemic therapy because of their endogenous origin, biocompatibility, and intrinsic targeting capacity. Cell-derived plasma membrane nanovesicles complement EVs by preserving the source cells membrane architecture and receptor landscape, creating customizable scaffolds for biomimetic drug delivery. However, the full potential of these lipid nanovesicles has been challenging because current isolation workflows are labor-intensive, low-yield, and often lack purity, forming a critical bottleneck for clinical translation and standardized manufacturing. To overcome these challenges, we developed a programmable electrostatic and light-activated platform for isolating lipid vesicles directly from complex biological fluids in a rapid, high-purity, and scalable manner. Our approach employs photocleavable lipid nanoprobes (PLNs) that insert into vesicle membranes in a size-dependent fashion and, together with a cationic polymer, enable efficient capture on a solid support. A brief light exposure cleaves the probes to trigger on-demand release and fractionation of intact vesicles with high speed and precision. Using this platform, we demonstrate high-purity EV isolation with preserved membrane protein functionality, as well as single-step enrichment of right-side-out (RSO) cell membrane nanovesicles that maintain native membrane orientation for effective drug delivery. The capability to rapidly isolate and tailor vesicle subpopulations by size and orientation establishes a unified materials platform for precision nanomedicine and advanced therapeutics, paving the way toward clinical-grade vesicle production and next-generation liquid biopsy applications.

bioengineering↗

Alteration of skin fibroblast steady state contributes to healing outcomes

Fibroblasts display complex functions associated with distinct gene expression profiles that influence matrix production and cell communications and the autonomy of tissue development and repair. Thrombospondin-2 (TSP-2), produced by fibroblasts, is a potent angiogenesis inhibitor and negatively associated with tissue repair. Single-cell (sc) sequencing analysis on WT and TSP2KO skin fibroblasts demonstrate distinct cell heterogeneity. Specifically, we found an enrichment of Sox10+ multipotent progenitor cells, identified as Schwann precursor cells, in TSP2KO fibroblasts, while fibrosis-related subpopulations decreased. Immunostaining of tissue and cells validated the increase of this Sox10+ population in KO fibroblasts. Furthermore, in silico analysis suggested enhanced pro-survival signaling, including WNT, TGF-{beta}, and PDGF-{beta}, alongside a reduced BMP4 response. Additionally, the creation of two TSP2KO NIH3T3 cell lines using the CRISPR/Cas9 technique allowed functional and signaling validation in a less complex system. Moreover, KO 3T3 cells exhibited enhanced migration and proliferation, with elevated levels of pro-regenerative molecules including TGF-{beta}3 and Wnt4, and enrichment of nuclear {beta}-catenin. These functional and molecular alterations likely contribute to improved healing and increased neurogenesis in TSP2-deficient wounds. Overall, our findings describe the heterogeneity of dermal fibroblasts and identify pro-regenerative features of TSP2KO fibroblasts.

pathology↗

Integrin β3 Targeting Biomaterial Preferentially Promotes Secretion of bFGF and Proliferation of iPSC-Derived Vascular Smooth Muscle Cells

Human-induced pluripotent stem cell-derived-vascular smooth muscle cells (hiPSC-VSMC) have been shown to promote angiogenesis and wound healing. However, there is a paucity of research on how the extracellular matrix (ECM) microenvironment may impact the hiPSC-VSMCs function. In this study, our objective was to understand the effect of specific ECM ligand-integrin interaction on hiPSC- VSMCs paracrine secretion, cell proliferation, and morphology. We here showed a precise modulation of hiPSC-VSMC in a fibronectin functionalized fibrillar collagen scaffold by targeting their integrin {beta}3. The secretion of proangiogenic growth factor, basic fibroblast growth factor (bFGF) was found to be fibronectin dependent via v{beta}3 integrin interactions. Also, our data indicate the possible role of a positive feedback loop between integrin {beta}3, bFGF, and matrix metalloproteinase-2 in regulating hiPSC- VSMCs morphology and cell proliferation. Finally, the secretome with improved proangiogenic activity shows potential for future regenerative applications.

bioengineering↗