Rapid and chronological expression of angiogenetic genes is a major mechanism involved in cell sheet transplantation in a rat gastric ulcer model

Abstract

Introduction: Cell sheet technology has been applied in the treatment of patients with severe cardiac failure. Although the paracrine effect of cell sheets accelerating angiogenesis is thought to be the intrinsic mechanism for improvement of cardiac function, little is known about how a cell sheet would function in the abdomen. Methods: We used acetic acid-induced gastric ulcer rat model to elucidate the mechanisms of myoblast sheet transplantation in the abdomen. Myoblast sheet was implanted onto the serosal side of the gastric ulcer and the effect of sheet transplantation was analyzed. The maximal diameter of the ulcer and the changes in the gene expression of various growth factors in transplanted site was analyzed. The progenitor marker CD34 was also examined by immunohistochemistry. Results: Cell sheet transplantation accelerated the ulcer healing. qPCR showed that angiogenic growth factors were significantly upregulated around the ulcer in the transplantation group. In addition, at first, HIF-1a and SDF-1 continued to increase from 3 h after transplantation to 72 h, then VEGF increased significantly after 24 h with a slight delay. An immunohistochemical analysis showed a statistically significant increase in CD34 positivity in the tissue around the ulcer in the transplantation group. Conclusion: Myoblast sheet secreted various growth factors and cytokines immediately after transplantation onto the serosal side of artificial ulcer in the abdomen. Autonomous secretion, resulting in the time-dependent and well-orchestrated gene expression of various growth factors, plays a crucial role in the cell sheet function. Cell sheet transplantation is expected to be useful to support angiogenesis of the ischemic area in the abdominal cavity.

Keywords

• Regenerative medicine
• Cell sheet technology
• Growth factors
• Gastrointestinal tract