Jeannerat Annick, Meuli Joachim, Peneveyre Cédric, Jaccoud Sandra, Chemali Michèle, Thomas Axelle, Liao Zhifeng, Abdel-Sayed Philippe, Scaletta Corinne, Hirt-Burri Nathalie, Applegate Lee Ann, Raffoul Wassim, Laurent Alexis
Preclinical Research Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland.
Plastic and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland.
Pharmaceutics. 2023 Jul 3;15(7):1873. doi: 10.3390/pharmaceutics15071873.
Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative medicine applications. The aim of this study was to establish bioengineering and surgical proofs-of-concept for an artificial graft (Neoligaments Infinity-Lock 3 device) bearing cultured and viable FE002 primary progenitor tenocytes. Technical optimization and in vitro validation work showed that the combined preparations could be rapidly obtained (dynamic cell seeding of 10 cells/cm of scaffold, 7 days of co-culture). The studied standardized transplants presented homogeneous cellular colonization in vitro (cellular alignment/coating along the scaffold fibers) and other critical functional attributes (tendon extracellular matrix component such as collagen I and aggrecan synthesis/deposition along the scaffold fibers). Notably, major safety- and functionality-related parameters/attributes of the FE002 cells/finished combination products were compiled and set forth (telomerase activity, adhesion and biological coating potentials). A two-part human cadaveric study enabled to establish clinical protocols for hand ligament cell-assisted surgery (ligamento-suspension plasty after trapeziectomy, thumb metacarpo-phalangeal ulnar collateral ligamentoplasty). Importantly, the aggregated experimental results clearly confirmed that functional and clinically usable allogeneic cell-scaffold combination products could be rapidly and robustly prepared for bio-enhanced hand ligament reconstruction. Major advantages of the considered bioengineered graft were discussed in light of existing clinical protocols based on autologous tenocyte transplantation. Overall, this study established proofs-of-concept for the translational development of a functional tissue engineering protocol in allogeneic musculoskeletal regenerative medicine, in view of a pilot clinical trial.
手部肌腱/韧带结构断裂（撕裂、割伤）通常需要手术重建和移植，以恢复手指的机械功能。临床级人原代祖细胞肌腱细胞（FE002冷冻保存的祖细胞来源）此前已被提议用于同种异体组织工程和再生医学应用中的多种治疗用途。本研究的目的是为一种承载培养的、有活力的FE002原代祖细胞肌腱细胞的人工移植物（Neoligaments Infinity-Lock 3装置）建立生物工程和手术概念验证。技术优化和体外验证工作表明，可以快速获得联合制剂（每平方厘米支架动态接种10个细胞，共培养7天）。所研究的标准化移植物在体外呈现均匀的细胞定植（细胞沿支架纤维排列/包被）以及其他关键功能特性（肌腱细胞外基质成分，如I型胶原和聚集蛋白聚糖沿支架纤维的合成/沉积）。值得注意的是，汇编并阐述了FE002细胞/成品组合产品的主要安全性和功能性相关参数/特性（端粒酶活性、粘附和生物包被潜能）。一项分为两部分的人体尸体研究能够建立手部韧带细胞辅助手术的临床方案（大多角骨切除术后韧带悬吊成形术、拇指掌指关节尺侧副韧带成形术）。重要的是，汇总的实验结果清楚地证实，可以快速且有力地制备用于生物增强手部韧带重建的功能性和临床可用的同种异体细胞-支架组合产品。根据基于自体肌腱细胞移植的现有临床方案，讨论了所考虑的生物工程移植物的主要优点。总体而言，鉴于一项初步临床试验，本研究为同种异体肌肉骨骼再生医学中功能性组织工程方案的转化发展建立了概念验证。
