Ingrid Meulenbelt

The Leiden ex vivo human growth plate model in severe tall stature: a proof-of-concept study

Margo Tuerlings, Y.F. Ramos, Helena E. D. Suchiman, Sayedeh Sana Sayedipour et autres

ABSTRACT Background Viable human growth plate (GP) tissue is rarely available for translational research, limiting direct investigation of human longitudinal bone growth and pediatric growth disorders. In this proof-ofconcept study, we aimed to determine feasibility to establish a clinically integrated ex vivo …

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Spatial transcriptomics defines the mechanisms of hiPSC-derived stem cell-mediated repair in human articular cartilage

Yolande Ramos, Sayedeh Sana Sayedipour, Georgina Shaw, Margo Tuerlings et autres

ABSTRACT We here determined therapeutic efficacy and mode-of-action of human induced pluripotent-derived therapeutic stem cells (hiMSCs) across in vivo mouse and ex vivo human osteoarthritis models. hiMSC treatment in DMM-mice significantly reduced OARSI damage scores, which was affirmed by a decrease in …

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Dynamic suspension culture enhances scalable maturation of hiPSC-derived cartilage organoids for regenerative medicine

Giorgia Mazzini, Evelyn Houtman, Marcella van Hoolwerff, Merel Janssen et autres

Abstract Background Cartilage tissue engineering requires scalable culture strategies to produce high-quality organoids. Human induced pluripotent stem cells (hiPSCs) provide a renewable source of chondrogenic cells. However, conventional static 3D culture limits tissue maturation, reproducibility, and scalability. Dynamic culture systems may help …

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Comparative Assessment of Cartilage Quality in Human Induced Chondrocytes (hiCHOs) and Primary Articular Chondrocytes (hACs) Following Fibronectin-Based Selection

Giorgia Mazzini, Margo Tuerlings, Vicki van der Stap, Ilja Boone et autres

expansion. Fibronectin (FN)-based selection may enrich progenitor-like cells with better matrix-forming ability, but its long-term effect on ECM production by hiPSC-derived chondroprogenitors (hiCPCs), their derived chondrocytes (hiCHOs), and primary articular chondrocytes (hACs) from lesioned or preserved areas remains unclear.MethodsWe here compared cartilage …

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NUCLEAR FACTOR-I TRANSCRIPTION FACTORS DIRECT CHONDROGENIC CELL-FATE FROM NEUROGENIC TRAJECTORY

Rick Mulders, Mathew Nickel-Maunu, Marcella van Hoolwerff, Yolande F. Ramos et autres

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Supramolecular Engineering of Fluid Pressure in Filamentous Hybrid Double Network Hydrogels for 3D Chondrocyte Culture

Ciqing Tong, Ying Chen, Merel L. Janssen, Isabel Sariol et autres

Filamentous supramolecular polymers provide a modular synthetic platform that can emulate various extracellular matrix biopolymers in their structure and function. However, hydrogels based on their entangled one-dimensional nanostructures are mechanically weak and challenged in replicating the properties of native tissues that surmount …

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Application of human induced pluripotent stem cells for tissue modeling and therapy: are we on track?

Mathew Nickel Maunu, Ingrid Meulenbelt, Yolande F. M. Ramos

Stem cells are key for development of disease modeling and therapies. While promising, however, current application of cutting-edge hiPSC technologies is, among others, confounded by cellular heterogeneity leading to concerns about their suitability for experimental and clinical applications. Variations across donors, tissue …

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Nuclear Factor I genes drive chondrogenic cell-fate commitment

Rick Mulders, Mathew Nickel-Maunu, Marcella van Hoolwerff, Giorgia Mazzini et autres

Abstract Human induced pluripotent stem cells (hiPSCs) offer a powerful platform to model chondrogenesis and enable regenerative strategies, yet regulation of cell-fate commitment remains elusive. Here, we systematically mapped cell-fate trajectories from 7 time points during a 49-day chondrogenic hiPSC differentiation protocol …

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POST-TRAUMATIC KNEE OSTEOARTHRITIS GENOME-WIDE SIGNAL IN LONG NONCODING RNA TEX41 REGULATES TRANSCRIPTIONAL REPRESSOR ZEB2: A FUNCTIONALLY RELEVANT LINK TO INJURY

Margo Tuerlings, Daniel Dochtermann, Chelsea T. Nguyen, Alison Rocco et autres

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TRANSLATIONAL ADVANCEMENT OF HIPSC-DERIVED CARTILAGE COMBINING DYNAMIC BIOREACTOR CULTURE AND HUMAN EX VIVO MODELS OF OSTEOARTHRITIS

Giorgia Mazzini, Sana Sayedipour, Helena E. D. Suchiman, Marcella van Hoolwerff et autres

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HiMSC and EV derived treatments increase Quality of Life and reduce amount of Knee Replacement Surgeries compared to current standard of care for knee osteoarthritis patients in The Netherlands

Iris W. A. Boot, Georgina Shaw, Yolande F. M. Ramos, Mary Murphy et autres

OBJECTIVES: Current osteoarthritis treatments are designed to reduce pain and improve mobility instead of promoting the regeneration of cartilage. Cell-based therapies are being developed for the treatment of osteoarthritis. The aim of this study was to assess the cost-effectiveness of mesenchymal stromal …

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A damaging mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells

Zainab Harissa, Niek G.C. Bloks, Nancy S. Steward, Sara F. Tufa et autres

Osteoarthritis (OA) is a complex disease associated with genetic, biological, and mechanical risk factors that act, in part, to alter chondrocyte homeostasis. Our recent exome sequencing studies identified a damaging genetic variant in COL6A3, a monomeric unit of collagen type VI and …

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