Autologous skeletal myoblast sheets were developed in our department in 2003, and clinical research for humans began in 2007. About 50 patients with severe heart failure have been treated with this technique so far, and the effectiveness in cases of heart failure was clear. After industry and physician-led clinical trials, the world's first regenerative myocardial treatment product (Heart Sheet) was registered. Looking forward, we will continue fundamental and clinical research to further enhance the applicability of this treatment.
Heart Sheet, Cytokine angiogenesis and cytoprotection, Recipient cardiac tissue, Stem cell accumulation, Angiogenesis
In contrast to conventional (skeletal) myoblast sheets, induced pluripotent stem cell (iPS cell) cardiomyocyte sheets are able to actively contribute to contraction in the cardiac cycle, so have significant potential as a myocardium replacement therapy, and have already shown their effectiveness in improving cardiac function in large animal experiments. In collaboration with the Kyoto University Center for iPS Cell Research and Application (CiRA), we provide iPS cells for use in humans and research their clinical application, while closely cooperating with industry, academia, and government (AMED regenerative medicine network (A) iPS myocardial regeneration therapy).
In collaboration with the Osaka University Faculty of Engineering, we are also woring to develop 3D-printed iPS myocardium. We expect to use the 3D tissue created in this way, both for surgical treatment and pharmaceutical testing. Considering
the trajectory of this technology, in the not-too-distant future, a completely 3D-printed biological heart may be realised.
In addition to this, in cooperation with industry, we are developing further treatment methods using new pharmaceuticals and cell-types.
CoMIT: Center of Medical Innovation and Translational Research
With close cooperation between industry, academia, and government, from now and into the future, we will continue to develop innovative treatments for heart disease.
Among childhood heart disease, there are diseases of the myocardium that tend to become severe and necessitate heart transplants. Dilated cardiomyopathy is one such heart disease. In order to ameliorate the symptoms of cardiac insufficiency due to dilated cardiomyopathy, the condition is first treated with pharmaceuticals. However, it is not possible to treat the fundamental condition of the myocardium in this way, so when cases become severe a heart transplant must be considered. We often employ implanted ventricular assist devices (VAD) for children; however, this treatment is generally intended as a “bridge” to heart transplantation, so in most cases the function of the actual heart does not improve.
Regenerative medicine is intended to act directly on the myocardium, with the hope of improving actual heart function. At Osaka University, we have developed a myoblast cell-sheet therapy, which aims to improve myocardial function by applying
myoblasts (obtained from the patient's own skeletal muscle) in sheet form, directly to the heart surface.
In September 2015, the “Heart Sheet” became eligible for insurance coverage, and now we are conducting clinical trials to extend this treatment to children with dilated cardiomyopathy. After completion of the clinical trial, we plan to continue development until we can provide insurance-covered treatment for pediatric patients too.
If you have a child suffering from heart failure, please do not hesitate to contact us for a consultation.
As the incidence of congenital heart disease increases, the number of patients needing heart valve surgery at a relatively young age is also increasing year by year. Currently, there is a significant possibility that prosthetic valves implanted
under coverage of national insurance will require reoperation after about 10 years. For this reason, new prosthetic heart valves with high durability are considered to a be high priority.
Using cellular engineering procedures, fresh decellularized heart valves are made, in which transplant rejection is unlikely to occur. After transplantation, it has been found that the recipient's own cells make their way into the decellularized valve structure, self-organize, and thereby maintain the valve function.
External appearance of the
decellularized valve structure
Fresh decellularized heart valves
Because these decellularized valves are reported to give better results compared to existing artificial valves, they have the potential to become established as an essential component of next-generation surgical techniques.
Since 2013, our department has been conducting clinical research on cardiac valve transplant surgery using fresh decellularized human heart valves, for congenital heart disease patients with postoperative pulmonary valve insufficiency.
In October 2014, in collaboration with Hannover Medical School, we performed the first decellularized valve transplant in Japan, using a valve provided from Germany, and the heart valves used in the two most recent cases were provided by the recipients of heart transplants at Osaka University. During heart transplant, the heart of the recipient is removed together with the valves, but often the function of the valves is sufficient, even when heart transplantation is necessary due to muscular diseases. The decellularization and use of heart valves removed during transplantation is now considered extremely important from a medical resource perspective. Also, compared with other devices, there seems to be a reduced need for reoperation, which is also expected to lead to a reduction in medical expenses.
Currently, our department is planning a physician-led clinical trial for securing insurance coverage for this treatment.