Application of Stem Cells and Cellular Engineering in Musculoskeletal Tissue Regeneration

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 740

Special Issue Editor


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Guest Editor
Orthopaedic Biotechnology Lab, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Via Cristina Belgioioso 173, 20157 Milan, Italy
Interests: orthopedics; musculoskeletal field; mesenchymal stem/stromal cells; regenerative medicine; clinical biochemistry
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Special Issue Information

Dear Colleagues,

Musculoskeletal tissues, including bone, cartilage, tendon, ligament, and muscle, possess limited intrinsic regenerative capacity, making their repair a major clinical challenge. In recent years, stem cell–based therapies and cellular engineering strategies have emerged as promising approaches to enhance tissue regeneration and restore functional integrity. Mesenchymal stem/stromal cells (MSCs), induced pluripotent stem cells, and tissue-specific progenitors have demonstrated significant potential due to their regenerative capacity, immunomodulatory properties, and paracrine activity. In parallel, advances in cellular engineering—such as gene editing, biomaterial-based scaffolds, bioreactors, and three-dimensional culture systems—have enabled the development of more sophisticated and physiologically relevant regenerative strategies. The integration of stem cells with engineered microenvironments allows precise control over cell fate, matrix deposition, and tissue organization, ultimately improving repair outcomes. Moreover, emerging insights into mechanobiology, cell–matrix interactions, and extracellular vesicle signaling are further expanding the therapeutic landscape. This Special Issue aims to highlight cutting-edge research and translational advances in the application of stem cells and cellular engineering for musculoskeletal tissue regeneration. Original research articles and comprehensive reviews addressing basic mechanisms, preclinical models, and clinical perspectives are welcomed, with the goal of fostering interdisciplinary collaboration and accelerating the translation of innovative regenerative therapies into clinical practice.

Topics of interest include, but are not limited to:

  • Stem cell therapies for musculoskeletal tissues;
  • Mesenchymal stem/stromal cells and progenitors;
  • Cellular and gene engineering approaches;
  • Biomaterials, scaffolds, and 3D culture systems;
  • Mechanobiology and cell–matrix interactions;
  • Preclinical animal models for musculoskeletal regeneration;
  • Extracellular vesicles and secretome‑based therapies.

Dr. Alessandra Colombini
Guest Editor

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Keywords

  • mesenchymal stem cells (MSCs)
  • tissue specific progenitors
  • cellular engineering
  • musculoskeletal tissue regeneration
  • tissue engineering
  • biomaterials
  • 3D culture systems
  • mechanobiology
  • extracellular vesicles
  • translational regenerative medicine

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Published Papers (1 paper)

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Research

16 pages, 3885 KB  
Article
Preclinical Tumorigenicity Study of an Advanced Therapy Medicinal Product for Diffuse Cartilage Lesions in an Osteoarthritic Environment
by Alessandra Colombini, Vincenzo Raffo, Vincenzo Pennone, Katia Mareschi, Luciana Labanca, Laura Mangiavini, Matteo Moretti, Camilla Recordati, Federico Armando, Laura de Girolamo and Arianna B. Lovati
Cells 2026, 15(5), 429; https://doi.org/10.3390/cells15050429 - 28 Feb 2026
Viewed by 527
Abstract
Background: Advanced therapy medicinal products require rigorous preclinical testing to exclude tumorigenicity. Human articular cartilage cells expanded at low density with human platelet lysate show enhanced proliferation, matrix production, and immunomodulatory properties, supporting their use for diffuse cartilage lesions in osteoarthritic joints. This [...] Read more.
Background: Advanced therapy medicinal products require rigorous preclinical testing to exclude tumorigenicity. Human articular cartilage cells expanded at low density with human platelet lysate show enhanced proliferation, matrix production, and immunomodulatory properties, supporting their use for diffuse cartilage lesions in osteoarthritic joints. This study evaluated tumorigenicity and biodistribution of cartilage cell spheroids generated using two platelet lysate sources. Methods: Cartilage cells were expanded at low density with two platelet lysates and assembled into spheroids. Cytogenetic stability was assessed by metaphase karyotyping following expansion. Immunodeficient mice received subcutaneous implantation and were monitored for 180 days. Human colon carcinoma cells and mouse fibroblasts were used as controls. Clinical follow-up, full organ histopathology, and immunohistochemistry were performed to detect human cell persistence. Results: Expanded cartilage cells showed predominantly normal karyotypes, with rare low-level mosaic chromosomal alterations not detected at the previous passage. Cartilage cell spheroids were well tolerated in vivo, with complete survival and no evidence of tumorigenicity, inflammation, or human cell persistence at implantation sites or distant organs. Control experiments confirmed the sensitivity of the model, and no systemic toxicity was observed. Conclusions: Spheroids derived from cartilage cells are non-tumorigenic, non-migratory, and biologically safe in immunodeficient mice. These findings support their development as cell-based cartilage therapies and align with regulatory recommendations for non-clinical safety evaluation. Full article
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