Porcine induced pluripotent stem cell-derived osteoblast-like cells prevent glucocorticoid-induced bone loss in Lanyu pigs

• Published in: PloS one 2018-08, Vol.13 (8), p.e0202155
• Main Authors: Liao, Yu-Jing, Tang, Pin-Chi, Chen, Yu-Hsin, Chu, Feng-Hsiang, Kang, Ting-Chieh, Chen, Lih-Ren, Yang, Jenn-Rong
• Format: Article
• Language: English
• Subjects: Animal models; Animal sciences; Animals; Biocompatibility; Biology and Life Sciences; Bone density; Bone loss; Bone mass; Calcium; Cancellous bone; CAT scans; Cell Differentiation; Cells, Cultured; Complications and side effects; Computed tomography; Cortical bone; Councils; Diaphysis; Diet; Female; Fibroblasts; Gene expression; Glucocorticoids; Glucocorticoids - adverse effects; Hogs; Induced Pluripotent Stem Cells - cytology; Laboratory animals; Livestock; Medicine and Health Sciences; Metaphysis; Osteoblasts - cytology; Osteoblasts - transplantation; Osteoporosis; Osteoporosis - etiology; Osteoporosis - therapy; Ovariectomy; Phenotypes; Physiology; Pluripotency; Porosity; Prednisolone; Prevention; Research and Analysis Methods; Stem cell transplantation; Stem Cell Transplantation - methods; Stem cells; Swine; Tomography; Transplantation; Vertebra; Vertebrae; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202155

The application of appropriate animal models and techniques for the study of osteoporosis is important. Lanyu pigs, a local miniature breed, have been widely used in various biomedical studies in Taiwan. This study aimed to induce bone loss in Lanyu pigs and to examine whether porcine induced pluripotent stem cell (piPSC)-derived osteoblast-like cells could recover bone mass of tibiae via local cell transplantation. piPSCs were directed to differentiate into osteoblast-like cells using osteogenic medium, and differentiated cells expressed osteogenic markers and phenotypes. Twenty mature female Lanyu pigs were divided into four groups, including control (C, 1% calcium diet), treatment 1 (T1, ovariectomy + 1% calcium diet), treatment 2 (T2, ovariectomy + 0.5% calcium diet), and treatment 3 (T3, ovariectomy + 0.5% calcium diet + 1 mg/kg of prednisolone) and were subjected to bone loss induction for twelve months. Micro-CT images revealed that the lowest trabecular bone parameters, such as trabecular bone volume, thickness, separation, number, and total porosity, were detected in the T3 group. The lowest proportions of cortical bone in the proximal metaphysis, proximal diaphysis, and distal diaphysis were also found in the T3 group. These results indicate that ovariectomy, calcium restriction, and prednisolone administration can be applied to induce proper bone loss in Lanyu pigs. After bone loss induction, pigs were subjected to cell transplantation in the left tibiae and were maintained for another six months. Results showed that transplanted piPSC-derived osteoblast-like cells significantly improved trabecular bone structures at transplanted sites and maintained cortical bone structures in the proximal metaphysis. In conclusion, the therapeutic potential of piPSC-derived osteoblast-like cells was confirmed via cell transplantation in the left tibiae of Lanyu pigs. These findings reveal the therapeutic potential of piPSCs for glucocorticoid-induced bone loss in pig models.