Development of angiogenic therapy using cell transplants such as autologous bone marrow and peripheral blood mononuclear cells, and CD34-positive cells for severe limb ischemia is underway, but its effectiveness is still insufficient.When severe limb ischemia is caused by arteriosclerosis obliterans, which is the most common type of severe limb ischemia, the standard treatment, revascularization, especially endovascular treatment, is highly effective, which is thought to be why it is difficult to demonstrate the effectiveness of angiogenic therapy using cell transplants, which regenerate at the capillary and arteriole level.

 

On the other hand, the angiogenic effect of cell transplantation is thought to be due more to the indirect contribution of angiogenic factors secreted by the transplanted cells than to the direct contribution of the transplanted cells themselves to form new blood vessels. However, it has been reported that most transplanted cells, such as mononuclear cells, quickly migrate into the systemic circulation and rarely remain in the ischemic tissue. Therefore, if the transplanted cells can be made to remain in the ischemic tissue for a long period of time, a dramatic improvement in the angiogenic effect can be expected.

 

Therefore, Professor Tsutomu Furuzono of Kindai University and Professor Shinya Fukumoto of Osaka Metropolitan University, in collaboration with Gunze Co., Ltd., have begun developing an injectable cell scaffold (ICS), an injectable substrate that can be attached to transplanted cells, with the aim of further improving angiogenic therapy using cell transplantation. ICS have a spherical structure with a diameter of approximately 50 μm, with a bioabsorbable polymer core and a surface coated with hydroxyapatite (HAp) single crystals. HAp has the ability to adhere cells, allowing transplanted cells to be supported on its surface, and by retaining transplanted cells in ischemic tissue for an extended period of time, they exhibit a high angiogenic effect.

 

Kenichi Yamahara, our company's representative director, proposed the clinical application of ICS to doctors and the manufacturer, BioX Co., Ltd. , to develop it into a medical device, and with support from the AMED Medical Device Development Promotion Research Project, he has been working on PMDA compliance and biological safety testing. ICS is characterized by its extremely low cost of production, and by using peripheral blood mononuclear cells obtained using an apheresis device commonly used in clinical settings as the transplant cells, it enables repeated, extremely low-cost and safe cell transplants, unlike conventional regenerative medicine products.

 

Currently, with the support of the AMED Translational Research Program, an exploratory investigator-initiated clinical trial using ICS for severe lower limb ischemia is being conducted at Hyogo Medical University Hospital and Oita Oka Hospital, with Kenichi Yamahara as the coordinating investigator ( jRCT2052230115 ). During this process, safety as well as efficacy was suggested, and so our company was founded with the aim of conducting the next confirmatory clinical trial and further obtaining manufacturing and marketing approval in the future.