Laurent Alexis, Abdel-Sayed Philippe, Grognuz Anthony, Scaletta Corinne, Hirt-Burri Nathalie, Michetti Murielle, de Buys Roessingh Anthony S, Raffoul Wassim, Kronen Peter, Nuss Katja, von Rechenberg Brigitte, Applegate Lee Ann, Darwiche Salim E
Regenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, CH-1066 Épalinges, Switzerland.
Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Épalinges, Switzerland.
Biomedicines. 2021 Apr 3;9(4):380. doi: 10.3390/biomedicines9040380.
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.
肌腱缺损需要长期的多模式治疗管理，且会带来高附带负担并频繁导致功能丧失。最近，在治疗急性和退行性肌腱组织疾病的手术技术发展的同时，也开发了特定的细胞疗法，以最佳地刺激结构和功能的恢复。培养的原代人胎儿祖细胞肌腱细胞（hFPT）已被初步考虑用于同种异体同源细胞疗法，并已被表征为体外稳定、一致且可持续的细胞来源。在此，研究了从单一器官捐赠中优化治疗细胞来源、多层祖细胞库的工业转化以及既定hFPT细胞来源（即FE002-Ten细胞类型）的初步临床前安全性。结果强调了FE002-Ten hFPT的高稳健性以及在优化的生物样本库工作流程中适合可持续扩大生产规模。分别在鸡胚和体外证明了hFPT没有毒性或致瘤性。此外，一项使用兔髌腱部分厚度缺损模型的为期6周的试点良好实验室规范（GLP）安全性研究初步证实了基于hFPT的标准化移植的临床前安全性，其中未观察到免疫反应、产品排斥或肿瘤形成。这些结果强化了瑞士多模式胎儿祖细胞移植计划的基本原理，并促使在临床前和临床环境中围绕此类细胞来源在肌肉骨骼再生医学方面进行进一步研究。
