Regenerative medicine with cell sheet engineering

Regenerative medicine with cell sheet engineering

Cornea regeneration

Corneal epithelial stem cell deficiency is caused by loss of the stem cells caused by trauma or autoimmune disease such as Stevens-Johnson syndrome.  Transparency of the corneal is impaired by invasion by conjunctival cells, and visual acuity is decreased.  We collaborate with Prof.  Kohji NISHIDA at the Osaka University to develop autologous oral mucosal epithelial cell sheet for transplantation to repair corneal surface.

Esophageal mucosa regeneration

Esophageal stenosis is a major complication of endoscopic submucosal dissection (ESD) for removing esophageal cancer and decrease QOL of patients after the dissection.  We collaborate with Prof. Masakazu YAMAMOTO and Dr. Takeshi OHKI at Hospital of Tokyo Women’s Medical University to investigate potency of transplantation of oral mucosal epithelial cell sheet for preventing esophageal stenosis after ESD.  In accordance with the investigation, the clinical studies were performed at Hospital of Tokyo Women’s Medical University and Nagasaki University, and the clinical trial was performed by CellSeed Inc.  The transplantation of the cell sheets is also useful for preventing stenosis after balloon dilation, and the clinical studies have been performed at National Center for Child Health and Development and Tomishiro Central Hospital.

Cartilage regeneration

Since osteoarthritis is highly prevalence and progressive, a new method for the treatment is highly expected particularly in the aging society.  We collaborate with Prof. Masato SATO at the Tokai University to achieve cartilage regeneration using chondrocyte sheets.  To date, we confirmed that autologous chondrocyte sheets can be efficiently transplanted to the damaged cartilage tissue and the cell sheet transplantation was effective to treat osteoarthritis.  This cell sheet-based therapy is expected to become a new option to regenerate cartilage in the near future.

Myocardium regeneration

Severe heart failure is the one of the poor prognosis diseases and novel therapeutic strategies have been expected. We collaborate with Prof. Yoshiki SAWA at Osaka University to develop a new method using skeletal myoblast sheets for the treatment of severe heart failure. The transplanted myoblast cell sheets secrete various types of cytokine and improve heart function and QOL of patients with dilated cardiomyopathy and ischemic heart disease. Currently, myoblast cell sheet (Terumo Co.) has been approved as the first commercialized cell sheet-based regenerative medicine product from Ministry of Health, Labor and Welfare in 2015. Furthermore, human iPS cell-derived cardiac cell sheet transplantation first in human clinical trial started in 2020. We are developing thickened and functional 3D cardiac tissue for the direct circulation support of heart failure patients.

Treatment of middle ear disease

Tympanoplasty is surgical method for cholesteatoma and adhesive otitis media.  Regeneration of middle ear mucosa after the surgery is important for preventing complication such as re-adhesion of tympanic membrane and recrudescence of cholesteatoma.  Collaborative research with Prof. Hiromi KOJIMA at Jikei University School of Medicine developed regenerative therapy for middle ear mucosa by transplantation of nasal mucosal epithelial cell sheets, and the clinical studies were performed.  Prof. Hiromi KOJIMA et al. and Japan Tissue Engineering Co., Ltd. will start clinical trial for promoting this therapy.

Paradentium regeneration

Approximately 40% people aged 40 or older suffer from periodontitis, and there is no effective therapy for large defect of the alveolar bone.  Prof. Isao ISHIKAWA and Prof. Takanori IWATA et al. investigated potency and safety of transplantation of periodontal ligament-derived cell sheets for regeneration of the paradentium in preclinical and clinical study.  Clinical trial has been performed by Prof. Tomohiro ANDO at Hospital of Tokyo Women’s Medical University and Prof. Takanori IWATA at Tokyo Medical and Dental University for serious periodontitis with no effective therapy by using allogeneic ligament-derived cell sheets fabricated by CellSeed Inc.

Treatment of pulmonary leak

In chest surgery, lung air leaks are often observed after thoracic procedures and are a peculiar complication in addition to other complications such as bleeding and infection.  Although it is expected that the tight sealing of intraoperative air leaks will be effective to reduce the chest cavity drainage period, there has been no clinical use of adhesive materials that have both strong adhesiveness and low toxicity.  Prof. Masato KANZAKI at Tokyo Women’s Medical University and his collaborators have demonstrated that autologous dermal fibroblast sheets was effectively used to prevent the air leak after operation in the preclinical study.  Currently to move on to clinical study, they are working on verifying the optimization of cell-sheet-fabrication conditions and others, utilizing human dermal fibroblasts.