Characterization Of Tendon Stem/progenitor Cells And Their Interaction With Scaffold

Tendons injuries occur frequently during sports and other rigorous activities, which can lead to instability and abnormal joint movement. Natural tendon healing often results in the formation of scar tissue, which has inferior mechanical properties and is susceptible to re-injury. Therefore, the functional repair of tendon injury remains a major challenge. Currently, there are various treatment regimes for repairing tendon injuries, including autografts, allografts, xenografts, suture techniques, tendon-to-bone fixation and tendon prostheses. However, these therapeutic outcomes are limited by immunological reaction, inevitable donor site morbidity, poor graft integration and high rates of recurrent tearing. Up to date, tissue engineering has emerged as a promising strategy for tendon regeneration.Tissue engineering utilizes a combination of seed cells, bio-scaffolds, and bioactive molecules to replace or repair injured tissues. Previous tendon tissue engineering researchers also proved the efficacy of cell transplantation with scaffolds. However there are two challenges remained to be overcome before clinical translation. One is how to get the enough seed cells? The other is how to design the teno-lineage inductive scaffold?The current study includes four parts:We firstly isolated human fetal and adult tendon derived tendon stem/progenitor cells, and showed that they possess several universal criteria of stem cells, including clonogenicity, self-renewal and multipotent differentiation capacity. Then we investigated the property of nestin positive tendon stem/progenitor cells (TSPCs) and the role of Nestin in regulation of TSPCs biological activity. It is demonstrated that nestin is essential to TSPCs differentiation and survival, especially in collegen fibril assembly. In the third part, we explored the interaction between TSPCs and bioscaffold and design aligned nanofibers to mimic the native tendon matrix. The activity of hTSPCs on aligned nanofibers was investigated and compared with randomly-oriented nanofibers. Also, the efficacy of aligned nanofibers in inducing tendon tissue regeneration was investigated in vivo. We found aligned nanofiber initiated teno-lineage differentiaiton and is suitable for tendon tissue engineering. The regulation of tendon stem cell differentiation by the alignment of nanofibers; Finally, the impact of collagenous matrices derived from different tissues (tendon, bone and dermis) was investigated on the fate decision of human tendon stem/progenitor cells (hTSPCs) and selected for tendon repair. Based on the specific biological function of the tendon-derived decellular matrix, a tissue-engineered tendon with TSPCs and tendon-derived matrix was successfully constructed for Achilles tendon reconstruction. This study provided important information for the future tissue engineering application with stem cells and bioscaffold.