Angiogenesis therapy using cell transplants of autologous bone marrow/peripheral blood mononuclear cells, CD34-positive cells, etc. for severe lower limb ischemia is being developed, but its effectiveness is not yet sufficient. In cases where severe lower limb ischemia is caused by arteriosclerosis obliterans, which is the most common cause of severe lower limb ischemia, the standard treatment of revascularization, especially endovascular treatment, is highly effective, so it is thought that it is difficult to demonstrate the effectiveness of angiogenesis therapy using cell transplants, which regenerates at the capillary and arteriole level.

 

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

 

Therefore, Professor Tsutomu Furuzono of Kinki University and Professor Shinya Fukumoto of Osaka Koritsu University have begun the development of an injectable cell scaffold (ICS), a substrate that can be attached to transplanted cells and implanted, with the aim of further improving angiogenesis therapy using cell transplantation. ICS has a spherical structure with a diameter of approximately 50 um, with a bioabsorbable polymer in the center and a surface covered with single crystals of hydroxyapatite (HAp). HAp has cell adhesion properties, so transplanted cells can be supported on its surface, and by retaining transplanted cells in ischemic tissue for a long period of time, it exerts a high angiogenesis effect.

 

Kenichi Yamahara, our company's representative director, proposed to doctors that ICS be made into a medical device for clinical application, and with the support of 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 practice as the transplant cells, it allows for repeated cell transplantation at a very low cost and with safety, which is different from conventional regenerative medicine products.

 

Currently, with the support of the AMED Translational Research Program, an investigator-initiated clinical trial using ICS for severe lower limb ischemia is being prepared at Hyogo College of Medicine Hospital, and manufacturing and marketing approval is expected in the future.