Brittle bone disease, medically known as osteogenesis imperfecta (osteogenesis imperfecta), is a rare congenital hereditary skeletal dysplasia disease, the main phenotype is type I collagen synthesis disorder, the incidence is about 1 in 10,000, worldwide There are about 5 million patients. At present, symptomatic treatment methods such as fracture prevention are mainly adopted for this disease, and there is no effective treatment plan. Researchers from the Pennsylvania State University School of Medicine found that bone marrow mesenchymal stem cells and type I collagen as an extracellular matrix were directly mixed and injected into the bone marrow cavity of the femur of mice with osteogenesis imperfecta (oim). Mesenchymal stem cells differentiate into osteoblasts and osteocytes and synthesize high-density new bone in vivo, which significantly improves the strength of long bones in mice. This illustrates the feasibility of using this strategy to treat osteogenesis imperfecta and other mesenchymal stem cell diseases.
The first author of the article, Dr. Li Feng, said, "There have been many uncertain results in previous studies on stem cell transplantation for the treatment of osteogenic insufficiency. These studies also failed to provide evidence that bone marrow mesenchymal stem cells can directly differentiate into osteoblasts and Osteocytes. Our group ’s research indicates that bone marrow mesenchymal stem cells differentiate into osteoblasts and osteocytes by themselves, synthesizing type I collagen to treat osteogenesis imperfecta. "The researchers isolated bone marrow stem cells from normal mice and labeled GFP Green fluorescent protein. In this way, the distribution and changes of bone marrow mesenchymal stem cells in the body can be tracked, and the influence and mechanism on new bone formation can be evaluated. This study found and suggested that: (1) Mesenchymal stem cells transplanted into the femur of OIM mice can directly participate in the formation of new bones after two weeks, and significantly improve the formation of new bones and the strength of long bones after six weeks. And density; (2) Type I collagen combined with bone marrow mesenchymal stem cells can further significantly increase the formation of new bone, manifested as a significant maximum load in the mechanical load destruction test, the principle may be by limiting the bone marrow mesenchyme after transplantation Stem cell loss, and provide normal extracellular collagen matrix to improve the environment of normal cells to promote stem cell growth and differentiation; (3) Mesenchymal stem cells not only directly participate in new bone formation after transplantation, but also may secrete bone-related The factor stimulates the migration and differentiation of endogenous stem cells to achieve the purpose of improving the treatment of osteogenesis imperfecta.
Shefelbine's group study in the UK used fetal blood stem cell transplantation to confirm that stem cells can express osteoblast-specific marker proteins in oim mice, synthesize type I collagen and improve the mechanical properties of the mouse bone. Another research report by Dr. Li Feng also confirmed that mesenchymal stem cells can secrete VEGF and SDF-1 through the paracrine effect to promote the recruitment of stem cells at the target site, and secrete BMP2 during the differentiation process to promote the differentiation of endogenous stem cells. The research findings of Penn State University are very exciting, and give the first direct evidence in the study of mesenchymal stem cells in the treatment of osteogenesis imperfecta, which will have a profound impact in the study of osteogenesis imperfecta.
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