Biology subjects

Tsimbouri, P. M.

Publications and source records attributed to Tsimbouri, P. M..

3 recordsLinked to original sources

bioRxiv2026

iPSC-Derived Chondroprogenitors as a Promising Cell Source for Cartilage Engineering: A Comparison with MSCs in Unmodified and Peptide-Functionalized Alginate Hydrogels

Articular cartilage degeneration is a hallmark of degenerative joint diseases, yet its limited regenerative capacity poses significant challenges for tissue engineering. While mesenchymal stem cells (MSCs) are the most commonly employed cell type in cartilage tissue engineering, they exhibit donor variability, restricted expansion capacity, and tendencies toward fibrocartilage formation and hypertrophic differentiation. Human induced pluripotent stem cell-derived chondroprogenitors (iCPs) represent a promising alternative, offering scalable production of developmentally relevant cells with intrinsic chondrogenic commitment. However, their performance within three-dimensional biomaterial scaffolds remains largely unexplored. Here, we compared chondrogenic differentiation of iCPs and MSCs within alginate hydrogels of varying stiffness (0.37 - 4.55 kPa) exhibiting physiologically relevant stress relaxation properties. Intermediate stiffness (2% alginate, ~2.17 kPa) optimally supported chondrogenesis for both cell types. While MSCs differentiated as single cells, iCPs spontaneously self-organized into cartilaginous aggregates without requiring a separate pellet pre-culture step, showing significantly higher hyaline indices and reduced COL10 expression, despite initial low viability in hydrogels. To further enhance chondrogenesis, we functionalized 2% alginate gels with RGD and HAVDI peptides mimicking integrin- and cadherin-mediated signaling. HAVDI/RGD functionalization significantly enhanced hyaline cartilage marker expression in both cell types, with iCPs exhibiting superior matrix composition characterized by elevated aggrecan and SOX9 expression and reduced COL10 and MMP13 compared to MSCs. These findings establish iCPs as a promising cell source for cartilage tissue engineering and disease modeling, particularly within biomaterials integrating mechanical and bioactive cues that recapitulate the native cartilage microenvironment.

cell biology↗

bioRxiv2026

Culture enhanced MSCs to boost haematopoietic engraftment in a model of the post-leukaemic bone marrow niche.

Relapse remains a leading cause of treatment failure in acute myeloid leukaemia (AML), making haematopoietic stem cell transplantation (HSCT) the only curative option for many patients. Yet HSCT efficacy is often limited by impaired engraftment, driven by AML-induced remodelling of the bone marrow stem cell niche. Mesenchymal stromal cells (MSCs) are key mediators of niche formation and could, in principle, restore a supportive microenvironment when introduced alongside HSC therapy; but this strategy remains largely untested. A key obstacle to MSC-based therapy is that MSCs acquire a senescent, pro-inflammatory phenotype during standard in vitro expansion. We addressed this by engineering a polymer-laminin presentation system that suppresses senescence and preserves a proliferative, regenerative MSC phenotype during expansion. Then, to investigate potential cell therapy use, we developed a bioengineered in vitro model as a new approach methodology (NAM) for studying disease-driven niche modification. The system consists of MSC spheroids embedded in a synthetic hydrogel within a transwell platform, allowing controlled co-culture of healthy or AML-derived haematopoietic cells, therapeutic MSCs, and chemotherapeutic agents. Using this platform, we modelled an AML-like niche and showed that MSCs expanded via the polymer-laminin system, when introduced alongside HSCs, significantly improved HSCT engraftment relative to both standard-expanded MSCs and HSCT performed without MSC support. These results establish MSC phenotype maintenance as a critical determinant of therapeutic efficacy, and position this NAM as a platform for pre-clinical screening of niche-targeted therapies in AML.

bioengineering↗

bioRxiv2026

Stiffness Drives Endothelial Senescence and Inflammation in Aging and Doxorubicin-Induced Vascular Dysfunction

Age-related arterial stiffening affects over [~] 60% of elderly individuals and is a major independent risk factor for cardiovascular mortality. Similarly, doxorubicin-induced cardiotoxicity affects up to [~] 48% of cancer patients, limiting therapeutic options. Here, we demonstrate that vascular stiffness mechanically amplifies endothelial senescence phenotypes, identifying the extracellular matrix as a potential therapeutic target for both cardiovascular aging and chemotherapy-induced vascular dysfunction. Using polyacrylamide (PAAm) hydrogels to mimick soft (3.3 kPa) and physiological (30 kPa) arterial stiffness, and glass to reproduce pathological stiffening, we show that substrate rigidity enhances senescence markers including {beta}-galactosidase activity, DNA damage, and inflammatory cytokine secretion in both therapy-induced and replicative senescence models. Critically, we identify a protective effect at physiological stiffness, where IL-6 and IL-8 secretion is minimized compared to both softer and stiffer conditions, suggesting an optimal mechanical therapeutic window. RNA sequencing reveals stiffness-dependent activation inflammatory pathways including chemotaxis and leukocyte migration. Our findings position vascular stiffening not just as a consequence but as driver of endothelial dysfunction, creating a positive feedback loop amenable to therapeutic intervention. These mechanobiological insights provide rationale for developing mechanical-based therapies in cardiovascular medicine and cardio-oncology, where targeting tissue mechanics alongside conventional approaches could improve clinical outcomes.

bioengineering↗