Table 1. Preclinical models reporting TRCD-based allogeneic MSC cell sheet therapy in various tissue sites.
| Target site | Disease model | MSC sheet preparation and properties in vitro | In vivo observation | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Origin | Size | Seeding density in 35 mm dish | Culture duration | Total grafted cell number | In vitro properties | Grafted MSC sheets | Therapeutic effects in host tissue | ||
| Heart [22] | Rat myocardial infraction model | Adipose tissue | 24 × 24 mm2 | 7.8 × 105 cells/dish | 3 days | 1 × 106 cells/rat | VEGF and HGF secretion | High cell viability at 2-day post-transplantation Cell sheet retention at least for 4 weeks |
Enhanced angiogenesis Suppression of fibrosis Improvement of cardiac function |
| Periodontal membrane [24,105,106] | Dog three-wall infrabony defect model | Periodontal ligament tissue | 8.8 cm2 (35 mm dish) | 3–4 × 104 cells/dish | 5 days | N.A. (trimmed triple-layered sheets) | Alkaline phosphatase activity Osteoblast/cementoblast markers Periodontal markers |
Cell sheet retention at least for 2 months | Periodontal regeneration including alveolar bone, cementum, well-oriented fibers, and nerve filament |
| Skin [108] | Rat wound-healing model of type 2 diabetes and obesity | Adipose tissue | 8.8 cm2 (35 mm dish) | 1.5 × 105 cells/dish | 7–8 days | 1.5 × 105 cells/rat | VEGF, HGF, TGF-ß1, IGF-1, EGF, and KGF secretion | Cell sheet retention at least for 2 months | Improved skin wound healing Enhanced angiogenesis |
| Bone [23] | Rat bisphosphonate-related osteonecrosis of the jaw model | Bone marrow | 8.8 cm2 (35 mm dish) | 2.5 × 105 cells/dish | 7 days | 1.5 × 106 cells/rat | VEGF and HGF secretion Bone regeneration marker (RANKL and OPG) gene expression |
Cell sheet retention at least for 2 months | Improved skin wound healing Bone regeneration Enhanced angiogenesis |
| Esophagus [109] | Porcine esophageal endoscopic submucosal dissection model | Adipose tissue | 3.5 cm2 (12 well plate) | 3.8 × 106 cells/dish | 12 h | 1.2 × 107 cells/rat (double-layered sheets x4) | N.A. | Cell sheet retention at least for 3 days | Less alimentary trouble and higher weight gain Reduced stricture and fibrosis formation |
| Intestine [110] | Porcine intestial anastomosis delayed wound-healing model | Adipose tissue | 8.8 cm2 (35 mm dish) | 2.4 × 106 cells/dish | 4 days | 2.4 × 106 cells/rat | Gene expression levels of FGF2 and TGF-ß1 | Cell sheet retention at least for 1 week | Enhanced collagen synthesis Increased the stiffness of intestinal anatomosis |
| Artery [104] | Rat femoral artery injury model | Adipose tissue | 8.8 cm2 (35 mm dish) | 1 × 106 cells/dish | 1–2 days | 6 × 106 cells/rat (triple-layered sheets x2) | N.A. | Cell sheet retention at least for 2 weeks | Artery reendothelialization Suppression of myofibroblast proliferation |
| Kidney [7] | Rat ischemia — reperfusion — injury model | Bone marrow | 8.8 cm2 (35 mm dish) | 1.2 × 106 cells/dish | 2 days | 7.2 × 106 cells/rat | VEGF and HGF secretion | Cell sheet retention at least for 2 weeks | Enhanced angiogenesis Suppression of microvascular injury Suppression of fibrosis Improvement of renal function |
| Neuron [111] | Rat stroke model | Adipose tissue | 8.8 cm2 (35 mm dish) | 1 × 106 cells/dish | 2 days | 3 × 106 cells/rat (triple-layered sheets) | IGF-1, HGF, VEGF, and TGF-ß1 secretion single-cell condition) |
Cell sheet retention at least for 2 weeks | Enhanced angiogenesis Enhanced neurogenesis Behavior improvement |