Grognuz A, Scaletta C, Farron A, Raffoul W, Applegate L A
Unit of Regenerative Therapy, Service of Plastic, Reconstructive and Hand Surgery, Department of Musculoskeletal Medicine, University Hospital of Lausanne, Switzerland.
Cell Transplant. 2016;25(3):463-79. doi: 10.3727/096368915X688515. Epub 2015 Jun 24.
Tendon injuries are very frequent and affect a wide and heterogeneous population. Unfortunately, the healing process is long with outcomes that are not often satisfactory due to fibrotic tissue appearance, which leads to scar and adhesion development. Tissue engineering and cell therapies emerge as interesting alternatives to classical treatments. In this study, we evaluated human fetal progenitor tenocytes (hFPTs) as a potential cell source for treatment of tendon afflictions, as fetal cells are known to promote healing in a scarless regenerative process. hFPTs presented a rapid and stable growth up to passage 9, allowing to create a large cell bank for off-the-shelf availability. hFPTs showed a strong tenogenic phenotype with an excellent stability, even when placed in conditions normally inducing cells to differentiate. The karyotype also indicated a good stability up to passage 12, which is far beyond that necessary for clinical application (passage 6). When placed in coculture, hFPTs had the capacity to stimulate human adult tenocytes (hATs), which are responsible for the deposition of a new extracellular matrix during tendon healing. Finally, it was possible to distribute cells in porous or gel scaffolds with an excellent survival, thus permitting a large variety of applications (from simple injections to grafts acting as filling material). All of these results are encouraging in the development of an off-the-shelf cell source capable of stimulating tendon regeneration for the treatment of tendon injuries.
肌腱损伤非常常见，影响着广泛且异质的人群。不幸的是，愈合过程漫长，由于纤维化组织的出现，其结果往往不尽人意，这会导致瘢痕和粘连的形成。组织工程和细胞疗法成为传统治疗方法的有趣替代方案。在本研究中，我们评估了人胎儿祖肌腱细胞（hFPTs）作为治疗肌腱疾病的潜在细胞来源，因为已知胎儿细胞能在无瘢痕再生过程中促进愈合。hFPTs在传代至第9代时呈现出快速且稳定的生长，从而能够创建一个大型细胞库以供现货供应。hFPTs表现出强大的肌腱生成表型且稳定性极佳，即使置于通常会诱导细胞分化的条件下也是如此。核型分析还表明，直至传代12代时其稳定性良好，这远远超出了临床应用所需的传代次数（第6代）。当与其他细胞共培养时，hFPTs有能力刺激人成年肌腱细胞（hATs），后者在肌腱愈合过程中负责新细胞外基质的沉积。最后，能够将细胞分布在多孔或凝胶支架中，且细胞存活率极高，从而允许进行多种应用（从简单注射到用作填充材料的移植物）。所有这些结果对于开发一种现货供应的、能够刺激肌腱再生以治疗肌腱损伤的细胞来源而言是令人鼓舞的。
