Wellcome  Institute of Neuroscience, Soochow University ID:游客 [登陆]

Therapeutic mechanism of EPC transplantation for ischemic stroke

来源:作者:刘晓红发布于:2014-11-25 人阅读

Topic: Therapeutic mechanism of EPC transplantation for ischemic stroke


Reporter:  Dr. Guo-Yuan Yang,Shanghai Jiao Tong University


Time:  Nov 25, 2014, 14:00 PM


Location: Meeting Room, Institute of Neuroscience, Soochow University

Dr. Guo-Yuan Yang, KC Wong Endowed Chair Professor of Shanghai Jiao Tong University, received his MD/PhD degree from Shanghai Medical University in 1987, and conducted his post-doctoral research at University of California at San Francisco (UCSF) from 1989 to 1991. From 1991 to 2001, Dr. Yang worked as a Research Investigator and Assistant Professor at the Medical Centre of University of Michigan. From 2001 to 2008, Dr. Yang worked as an Associate Professor and finally as a Professor at UCSF.

In 2008, Dr. Yang joined Med-X Research Institute as the Associate Dean and KC Wong Endowed Chair Professor. Since 2010, Dr. Yang also hold a concurrent post as a Board Director of the International Society of Cerebral Blood Flow and Metabolism (ISCBFM), as a trustee of the Chinese Society for Neuroscience (CSN), as a committee member of the Neurobiochemistry Group of Neurology Sub-Association of Chinese Medical Association, and the Cerebral Vascular Sub-Association of the Shanghai Medical Association. Furthermore, Dr. Yang is the Associate Editor of CNS Neuroscience and Therapeutics, Board Editor of Stroke, Aging and Disease, etc. His research has been supported by National Institutes of Health (NIH) of the United States, K. C. Wong Foundation, 973 Program of China, National Natural Science Foundation of China, and Shanghai Municipal Health Bureau.

The research interests of Dr. Yang mainly focus on the mechanisms of cerebrovascular diseases in both basic and clinical fields. Recently, Dr. Yang has developed focal angiogenesis and focal microvessel dysplasia model in rodent brain for cerebrovascular study. Dr. Yang is also working on exploring new treatment for stroke by taking advantages of neuroimaging, neural rehabilitation, biomaterials, and medical device.

The major achievements of Dr. Yang include: 1) developed middle cerebral artery occlusion and reperfusion model in mice; 2) developed intra-cerebral hemorrhage model in rat; 3) pioneered cerebral vascular malformation model in mice and studied the mechanism of vascular development and lesion; 4) Creatively applied gene therapy technology to treat cerebral injury induced by ischemic stroke; 5) Creatively took advantage of different growth factors and stem cells in intervention treatment for cerebral ischemia animals; 6) Creatively used synchrotron radiation angiography and two-photon microscopy to study the occurrence and development of cerebrovascular disease in vivo in real time. Dr. Yang has published more than 180 scientific papers, with a cumulative Influence Factor (IF) of more than 700. His works were cited more than 5000 times.

Rationale: Both microglia activation and EPC homing are hallmarks in post-ischemic brain. Hign mobility group box1 (HMGB1) from astrocytes appeared to promote EPCs migration. But whether HMGB1 promotes the therapeutic effects of EPC for stroke by influencing the paracrine function of EPC is not investigated.

Objective: to investigate whether HMGB1-mediated crosstalk between microglia and exogenous EPC is associated with improved neurovascular remodeling during cerebral ischemia following EPC transplantation.

Methods and results: EPC was co-cultured with LPS-stimulated BV2 cells using transwell system. Glycyrrhizin (GL) was used for inhibiting HMGB1 release by BV2 cells. Co-culture induced the up-regulation of IL-8 in EPC (p<0.05), which is blocked by treating BV2 cells with HMGB1 inhibitor GL. CM of EPC co-cultured with BV2 cells promoted the viability and tube formation of HUVE in vitro (p<0.05). Inhibition of HMGB1 release by GL or IL-8 knockdown by siRNA diminished the effect of EPC CM on HUVECs. In vivo study showed that EPC transplantation led to improved neurobehavioral recovery and increased neovasculaerization in peri-infarct region for tMCAO mouse at day-14 after cerebral ischemia (p<0.05). Better outcomes was not observed for tMCAO mouse transplanted with EPC in adjuvant with GL treatment, as compared with mouse treated with PBS or HUVEC (p>0.05).

Conclusion: Transplantation of peripheral blood-derived EPC is efficacious for treating ischemic stroke. Enhanced IL-8 secretion of EPC mediated by HMGB1 released from activated microglia is associated with the therapeutic mechanism of EPC transplantation.