Circulating mesenchymal stem cells in bone healing
Mesenchymal stem cells (MSCs) have been found in cord blood and peripheral blood (PB) of mammalian species including human, guinea pig, mice, rat, dog, horse and rabbit. The number of MSCs in PB (PB-MSCs) is rare and their biological role was not fully defined. We have found increased numbers of circulating MSCs in peripheral blood in patients with long bone fracture, non-union and in patients with cancers. The number of PB-MSCs was approximately 9 times higher in the cancer patients, suggesting there is systemic recruitment of MSCs during cancer development. We have compared the difference between the circulating MSCs and bone marrow derived MSCs and found that they share similar phenotype in vitro, but the gene expression profile between the two cell populations was significantly different. cDNA microarray analysis and quantitative RT-PCR confirmed 10 genes that are differentially expressed with more than 10 folds difference, such as cellular retinol-binding protein 1 (CRBP1), cadherin 2, bone morphogenetic protein 6 (BMP6), SRY-box containing gene 11 (Sox11), the aquaporin 1 (AQP1), et al. These genes are now being further investigated for their role in MSCs migration, homing and multiple-differentiation potential. In terms of potential clinical implications of PB-MSCs, we have demonstrated that allogenic PB-MSCs enhanced bone regeneration in rabbit ulna critical-sized bone defect model. We also demonstrated that BM-MSCs can be recruited via circulation toward the sites of bone fracture and participate fracture healing in rabbits. We have also demonstrated that systemically administrated allogenic MSCs could home to fracture sites and promote fracture healing. In conclusion, PB-MSCs are new cell source of cells that may play very important roles in development, repair and disease progression.
Gang Li is Professor in the Department of Orthopedics and Traumatology, Faculty of Medicine at the Chinese University of Hong Kong. He earned an MBBS at the Fourth Military Medical University, Xian, China (1991), and a D. Phil at the University of Oxford School of Medicine, England, UK (1998). The focus of his research are on studies of the biological mechanisms of distraction osteogenesis, stem cell biology, circulating mesenchymal stem cells (MSCs), the use of MSCs for cell therapy applications, musculoskeletal tissue regeneration and repair. He has published more than 220 peer-reviewed SCI articles with citations over 4500 and H index 40; 15 book chapters, edited 3 books on tissue engineering, bone biology, distraction histogenesis, and Ilizarov techniques. He is a council member of Chinese Orthopaedic Research Society; Tissue Engineering and Regenerative Medicine Society, Chinese Association of Biomedical Engineering; Chairman of ILLRS and ASAMI China Branch. He is associate editor for Journal of Orthopaedic Translation; editor for Calcified Tissue International, Bone and Joint Research, and Bone. He holds honorary or visiting Professorship at many prestigious universities such as Monash University, Australia; University of Malaya, Malaysia; Sichuan University, China; South-East University Medical School, China; The Airforce Medical University, China; Guangdong Medical University and Jilin University, China. His work received serval awards including the 1st Class Research Award in Science and Technology, Ministry of Education, China; 2nd Class Award in Medical Science and Technology, China Medical Association; 1st Class Award in China Medical Science, China International Exchange and Promotion Association for Medical and Healthcare.