Kugako Sugimoto, NOST Tokyo
Originally published on the site of NL Agency.
A Japanese research team of Osaka City University Graduate School of Medicine and others have developed a method that enhances the success of cell-based therapeutic angiogenesis, the growth of blood vessels. The research team injected nano-scaffolds, hydroxyapatite-coated poly(L-lactic acid) microspheres, together with bone marrow mononuclear cells into ischemic hindlimbs of mice. Substantially longer retention of implanted cells in the targeted area was observed than with existing methods. Since this retention is crucial for successful cell-based therapeutic angiogenesis, the proposed method is highly promising as treatment for patients who suffer ischemic vascular disease. The research team published the results in the U.S. Web journal, PLOS ONE, in April 2012.
Details
To treat ischemic vascular disease caused by atherosclerotic occlusion of the arteries that supply blood to the mycocardium and limbs, cell transplantation has been developed. However, the success remains limited due to the low remaining rate of injected cells in the targeted site. Between seventy and ninety percent of transplanted cells disappear from the injection site within one week. A longer retention time is a key issue for successful treatment that allows time for implanted cells to produce and release angiogenic growth factors that results in the promotion of capillary formation in the target area.
The researchers, including Assistant Professor Fukumoto from the Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine worked together with the Department of Biomedical Engineering, School of Biology-Oriented Science and Technology, Kinki University to develop nano-hydroxyapatite coated poly L-lactic acid (PLLA) microspheres, the so-called nano-scaffold, aiming for longer retention time of transplanted cells. They injected the nano-scaffolds together with bone marrow mononuclear cells to ischemic hindlimbs of mice. The sign of retention of transplanted cells appeared approximately fivefold higher than that of bone marrow mononuclear cells injected alone or when using mononuclear cells with PLLA without hydroxyapatite coating after seven days.
The approach for successful implant by increasing the retention time of injected implant cells is simpler compared to other approaches such as genetic manipulation of implant cells (overexpression of genes) and creating artificial extracellular matrix. The size of nano-scaffold ranges from fifty to one hundred micrometer in diameter (Figure 1). The hydroxyapatite coat consists of nanometers size hydroxyapatite (HAp nanoparticle) around the core PLLA.
Figure 1. Nano-Scaffold consists of the core PLLA and HAp nanoparticle coating. (source: Osaka City University)
PLLA is a biodegradable polymer and generates the scaffold that helps to stop outflow of implanted cells. PLLA has been used in tissue engineering. Due to its biodegradability, it is not necessary to remove it after healing. Furthermore, PLLA is not a product derived from organisms like in the case of collagens, decreasing the concern for infections. However, PLLA has low cell adhesion due to its hydrophobic property. To compensate this disadvantage, hydroxyapatite that has high adhesive properties coats PLLA, centered in a nano-scaffold. Since hydroxyapatite has mechanical weakness and brittleness due to its ceramic nature, the application of this material was limited. However, Japanese company developed a technique to crystallize highly-dispersed nano-scale hydroxyapatite, resulting in the decrease of physical vulnerability, which can be applied to coating for the flexible polymeric substances such as PLLA.
In Japan, there are around 500,000 patients with symptoms of Peripheral Artery Disease （PAD）. Between twenty and thirty percent of them have risks of amputation of limbs. Angiogenesis is one of the treatments for PAD, besides endovascular treatment and bypass surgery, which depends on the cases of patients.
The research team aims to start clinical testing in 2015 in collaboration with Osaka Institute of Technology, and companies Gunze and SofSera. The tests must provide information about appropriate timing of absorption and toxicity of PLLA, appropriate ratio of cells to nano-scaffolds, and preincubation time of cells and nano-scaffolds prior to implantation. Since this method dramatically changes the lives of patients, clinical use is highly expected.
Source:
1) Osaka City University – www.osaka-cu.ac.jp/news/20120419111936/research.html
