Table 3 Examples of tendon cell sheet models
From: Boosting tendon repair: interplay of cells, growth factors and scaffold-free and gel-based carriers
Experimental cell sheet | Outcome | Preparation of cell sheet | Study type and animal models | Reference |
|---|---|---|---|---|
Rabbit ADSCs sheet | Cell sheets were cultured over 3 weeks, and cell metabolic activity, cell sheet thickness, and early differentiation gene expression were analyzed. One week-old cell sheets displayed upregulation of early differentiation gene markers (Runx and Sox9). Cell sheet thickness and cell metabolic activity increased in the second and third week. | ADSCs were cultured in 6-well culture plates until 100% confluence. Confluent cells were then cultured in expansion medium supplemented with 50 mg/ml ascorbic acid for 3 weeks to facilitate cell sheet formation. | In vitro | Neo et al. 2016 |
Mouse MSC sheet | MSC sheet transplantation into musculotendinous junction at 4–8 weeks showed similar recovery of muscle mass and tension to the contralateral non-transplanted side. However, at 14–18 weeks, MSC sheet-treated group showed increased recovery of muscle mass and tension output. Engrafted MSCs primarily formed connective tissues and muscle fibres, and bridged the ruptured tendon-muscle fibre units. | The cells reached full confluence, detached from culture dishes with 2 mM EDTA, then collected and centrifuged into hybrid sheet/pellet like structure. | In vitro and in vivo; Mouse musculo-tendinous junction model | Hashimoto et al. 2016 |
Human ACL-derived CD34+ cell sheet | ACL-derived CD34+ cell sheet improved the ACL repair which was judged by histological assessment at week 2 and biomechanical evaluation at week 8 in a rat ACL injury model. | Cells were plated in temperature-responsive culture dishes at 37 °C for 17 h, and then incubated at 20 °C for 20 min, and afterwards the cell sheets detached spontaneously. | Rat ACL injury model | Mifune et al. 2013 |
Human rotator cuff-derived cell sheet | The cell sheets transplanted to the infraspinatus injury site induced angiogenesis and Col synthesis, and improved tendon-bone junction repair at 4 and 8 weeks postoperation. | Cells were cultured on 24-well temperature-responsive culture dishes at 37 °C for 17 h. Then, the plates were placed at room temperature for 20 min, and the cell sheets detached from the wells spontaneously. | Rat rotator cuff injury model | Harada et al. 2017 |
Rat TSPC GFP-labelled sheet | The TSPC sheet radiographically, histologically and biomechanically improved ACL healing in a rat model at week 2, 6 and 12 postoperatively. GFP-labelled TSPCs were detected at the graft-bone tunnel interface and in the intra-articular graft midsubstance in all samples at week 2. | Cells were plated in normal culture dishes in low-glucose medium. After 100% confluence, cell sheet was detached by rinsing with saline. | Rat ACL injury model | Lui et al. 2014 |
Rat TSPC sheet | TSPC sheet grafting into Achilles tendon defect significantly improved the histological features and Col content both at 2 and 4 weeks post-surgery, indicating that TSPC sheets can speed up tendon remodelling in the early stages of the healing process. | TSPC sheets were prepared by plating on temperature-responsive culture dishes. Cells were cultured for 3 days and then induced for cell sheet formation by treating with 25 mM ascorbic acid in complete culture medium at 37 °C. After 9 days, monolayer cell sheets were obtained by reducing the temperature from 37 °C to 20 °C for 20 min. | Rat Achilles tendon injury model | Komatsu, et al. 2016 |