Abstract
Tendon defects require multimodal therapeutic management over extensive periods and incur high collateral burden with frequent functional losses. Specific cell therapies have recently been developed in parallel to surgical techniques for managing acute and degenerative tendon tissue affections, to optimally stimulate resurgence of structure and function. Cultured primary human fetal progenitor tenocytes (hFPT) have been preliminarily considered for allogeneic homologous cell therapies, and have been characterized as stable, consistent, and sustainable cell sources in vitro. Herein, optimized therapeutic cell sourcing from a single organ donation, industrial transposition of multi-tiered progenitor cell banking, and preliminary preclinical safety of an established hFPT cell source (i.e., FE002-Ten cell type) were investigated. Results underlined high robustness of FE002-Ten hFPTs and suitability for sustainable manufacturing upscaling within optimized biobanking workflows. Absence of toxicity or tumorigenicity of hFPTs was demonstrated in ovo and in vitro, respectively. Furthermore, a 6-week pilot good laboratory practice (GLP) safety study using a rabbit patellar tendon partial-thickness defect model preliminarily confirmed preclinical safety of hFPT-based standardized transplants, wherein no immune reactions, product rejection, or tumour formation were observed. Such results strengthen the rationale of the multimodal Swiss fetal progenitor cell transplantation program and prompt further investigation around such cell sources in preclinical and clinical settings for musculoskeletal regenerative medicine.
Highlights
Drastic modifications within rapidly evolving lifestyles have continuously been driving the need for innovative therapeutic solutions in musculoskeletal medicine in recent years
Cell banking and tier nomenclature depended on the passage numbers rather than on cell population doubling values (PDV), since the seeding and harvest parameters were consistent throughout production passages (Figure S4)
The presented workflow was applicable for Passages 1 to 8, which are of interest for clinical applications
Summary
Drastic modifications within rapidly evolving lifestyles (e.g., sedentary occupation, high-risk sports, long-term pharmacologic drug use) have continuously been driving the need for innovative therapeutic solutions in musculoskeletal medicine in recent years This trend has been important for structural repair and functional restoration of tendons [1,2,3,4]. Delayed inflammatory reactions, low baseline metabolism, limited extracellular matrix (ECM) deposition, and complex structural reorganization or alignment of tendons limit the scope and efficacy of specific therapeutic interventions [20,24] Transplantation techniques such as tendon transfers (e.g., surgical harvest and grafting of autologous vestigial tendons) have been effectively limited by rapid graft degeneration. Surgical approaches would most probably benefit from additional stimulation by appropriate therapeutic cells, for optimal elasticity, mobility, and tensile strength restoration [25,26,27,28]
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