Department of Neurosurgery

The only hospital affiliated with the Red Cross Society of China, the Huashan Hospital was founded in 1907 and is one of 400 hospitals in Shanghai. It has 1,326 beds, with 21,000 in-patients per year and 1.56 million outpatients and a staff of 2,300. It carries out 15,000 operations per year.

Neurosurgery is an area of highest priority, and the Huashan Neurosurgical Hospital is the largest in China. Some idea of scale can be gained from the observation that it performs ~7,000 surgeries and removes 4,000 tumours operated per year. It has a heavy commitment to imaging technologies, including three PET scanners.

Professor Zhu trained clinically in China and Japan, obtained a PhD in Berlin, and postdoctoral training at Massachusetts General Hospital in the lab of Evan Snyder at Harvard.

He is performing ground-breaking research into the autologous application of adult neural stem cells (NSCs) in traumatic brain injury. He is also making significant progress in studying foetal and adult hNSCs in animal models of disease.

A) Foetal hNSCs. His strategy is to transplant selected (eg CD133+) fetal cells into ventricles in animal models of neurodegeneration. He finds that cells migrate widely into the injured area in animal ischemic models. He has made transgenic (GFP expressing) lines through AAV infection and also Tet-inducible GDNF/neurturin expressing NSCs to discover whether these lines could rescue Parkinsonian models. He has implanted a digitally-controlled tetracyclinreleasing chip implanted into monkeys for tight GDNF regulation. These are currently being used in monkey PD models.

B) Adult hNSCs. Clinical studies are conducted on autologous transplantation of invitro expanded NSCs from open brain trauma patients. Brain tissue is only isolated from patients with open traumatic head wounds with brain tissue clearly outside the skull. Approximately 30% of patients with such wounds generate expandable populations of NSCs, and there has been no effort to date to isolate such cells from patients without open traumatic head wounds (ie this is specifically a serendipitous isolation procedure and thus obviating the requirement for biopsy as a source of brain tissue). The collected tissue is washed in the patient’s own CSF, with progressive dilutions into PBS prior to cultivation in conventional EGF/FGF2 medium.

The cells are generally expanded for 1-2 months prior to ransplantation, with grafting performed under MRI stereotacticguidance. Approximately 5-15x106 cells (as neurospheres, not dissociated cells) are grafted around the periphery of the site of primary lesion. The first expandable sample of human brain tissue was the ‘chopstick injury’ through right frontal lobe. (It transpires that chopsticks are sometimes utilised in Shanghai restaurants to culminate otherwise unresolvable differences of opinion.) This patient recovered the ability to walk (over one year following operation), with functional MRI to follow recovery. Since then, these studies have been extended to eight cases, with matched controls (open-brain surgeries but no cells grafted following surgeries).

Significant efficacy has been observed, though Professor Zhu remains cautious, observing that the degree of spontaneous recovery is highly variable in these cases.

In one case, cells were magnetically labelled with superparamagnetic nanoparticles, and MRI was used to follow the progression of the cells. This was first conducted in primates, and no apparent side effects were observed. This work has been submitted to NEJM for publication. The clinical study with eight patients, however, remains unpublished.