Research contents

Goal of research and development

In this research project, we will conduct a first-in-human clinical study of “Angiogenic cell therapy using autologous DFAT cells for critical limb ischemia (CLI)” to determine the safety and efficacy of DFAT cells for therapeutic angiogenesis. The profile of the clinical study is as follows: for CLI patients, we use approximately 10 mL of lipoaspirates as the source material and culture it for about five weeks in an isolator installed in the cell processing facility (CPF) in our institution, and then we prepare DFAT cells with the necessary cell count, which we transplant into ischemic muscle of a patient. The primary endpoint is confirmation of safety, and we plan to evaluate adverse events that may have occurred by the 52nd week after transplantation. The secondary endpoint is the evaluation of efficacy, for which we plan to evaluate changes of severity classification, ischemic pain, and other items. We will investigate the safety and efficacy of DFAT cell therapy via clinical studies with the goal of clarifying the validity of a transition to a clinical trial.

Background of research and development

CLI, which is a severe form of ASO, is often difficult to treat and results in limb amputation. Recently, to preserve the limb, cell therapy has been attempted for refractory CLI in expectation of a proangiogenic effect. MSC can be cultured and prepared from a relatively small amount of bone marrow aspirate or adipose tissue, and the safety of transplantation is high; therefore, it is expected as cell source for therapeutic angiogenesis. However, MSC are a heterozygous cell population with considerable individual differences in their quality, and a decrease in their ability has been clarified particularly in diabetic patients. Therefore, regardless of patient status, a technique to produce MSC that shows stable and homogeneous ability is expected. The research group of Nihon University demonstrated that DFAT cells, which were obtained by culturing mature fat cells isolated from fatty tissue via a method called ceiling culture, acquired high proliferation potency and multipotency that are similar to those of MSC. Because DFAT cells abundantly produce homogeneous MSC-like cells from a small amount of aspirated adipose tissue, we can expect DFAT cells to be a highly practical cell source for regenerative medicine. DFAT cells secrete large amounts of various angiogenic factors and at the same time have the potential to differentiate into vascular structure cells that show stable and high angiogenic ability. In addition, we have confirmed in animal experiments that unlike iPS cells, even if DFAT cells are transplanted in an undifferentiated state, they do not cause tumorigenesis and can be transplanted safely. From these findings, we thought that cell therapy with DFAT cells could be an effective therapy for CLI and planned a clinical study of angiogenic cell therapy for CLI using autologous DFAT cells.

Future prospects of research and development

The DFAT technique is one that can abundantly produce MSC-like cells with homogeneous and stable performance from a small amount of adipose tissue and that has a possibility of satisfying such scientific requirements as “standardization of MSC”. Although DFAT cell research is being conducted in many countries, there is still no example of its administration in humans, and this study will be the world’s first clinical study using DFAT cells. The study results are expected to contribute to the spread of highly practical angiogenic cell therapy at low cost, regardless of the age and underlying diseases of patients. Moreover, the results have a possibility of universally developing most of the preceding cell therapies using MSC into safer and less expensive ones. In this research and development, we plan to start clinical application in patients with CLI, and in the future, we will extend its adaptation to such common diseases as sequelae of myocardial infarction and cerebral infarction. When these plans are realized, we can expect to overcome an unmet medical need and reduce medical costs. Thus, this study is thought to make a significant contribution to society from the viewpoints of not only the development of regenerative therapy but also medical economics.