Analysis of Adverse Events Related to 720 Cases of Neural Progenitor Cell Transplantation.

BACKGROUND: Cell therapies have shown to be able to improve neurological functions to some extent for patients with refractory central nervous system (CNS) diseases or damages. Meanwhile, increasing attention has been drawn to the operation-related and (or) cell-related adverse events when performing cell therapy. Our study is to explore the safety issue from 720 cases of neural progenitor cell (NPC) transplantation based on clinic manifestations and examinations. METHOD: A retrospective analysis of all adverse events associated with 720 cases of NPC transplantation by administering the cells into the ventricles was done. RESULTS: One hundred and sixty-six cases had postoperative crying and irritability, 69 with vomiting and 84 with fever. None of them had CNS infection, but 4 cases presented intracranial hemorrhage. One month after cell therapy, 568 cases did EEG test, in which 153 patients showed improvement, 74 had abnormal changes in and 341 cases had no changes in; two patients developed new-onset convulsions and 3 had recurrent convulsions; 6 cases had intracranial hemorrhage, but no other CNS sequelae left from the primary diseases. 180 patients were able to follow-up for their clinical evaluation and head MRI or CT examination 2 years after transplantation. All patients didn't show signs of tumorigenesis and no serious and irreversible operation- or cell-related adverse events. IN CONCLUSION: there are mild adverse reactions and reversible adverse events following cell transplantation, our study indicated that NPC transplantation is a safe therapy in clinical treatment. Further clinical trials are necessary to establish the safety of this therapy.

Radiosynthesis and biological evaluation of N-[18F]labeled glutamic acid as a tumor metabolic imaging tracer.

We have previously reported that N-(2-[18F]fluoropropionyl)-L-methionine ([18F]FPMET) selectively accumulates in tumors. However, due to the poor pharmacokinetics of [18F]FPMET in vivo, the potential clinical translation of this observation is hampered. In this study, we rationally designed and synthesized [18F] or [11C]labeled N-position L-glutamic acid analogues for tumor imaging. N-(2-[18F]fluoropropionyl)-L-glutamic acid ([18F]FPGLU) was synthesized with a 30±10% (n = 10, decay-corrected) overall radiochemical yield and a specific activity of 40±25 GBq/µmol (n = 10) after 130 min of radiosynthesis. In vitro cell experiments showed that [18F]FPGLU was primarily transported through the XAG(-) system and was not incorporated into protein. [18F]FPGLU was stable in urine, tumor tissues, and blood. We were able to use [18F]FPGLU in PET imaging and obtained high tumor to background ratios when visualizing tumors tissues in animal models.

Positron emission tomography imaging of cell death with [(18)F]FPDuramycin.

The noninvasive imaging of cell death, including apoptosis and necrosis, is an important tool for the assessment of degenerative diseases and in the monitoring of tumor treatments. Duramycin is a peptide of 19-amino acids. It binds specifically to phosphatidylethanolamine a novel molecular target for cell death. N-(2-(18)F-Fluoropropionyl)duramycin ([(18)F]FPDuramycin) was prepared as a novel positron emission tomography (PET) tracer from the reaction of duramycin with 4-nitrophenyl 2-[(18)F]fluoropropionate ([(18)F]NFP). Compared with control cells (viable tumor cells), the in vitro binding of [(18)F]FPDuramycin with apoptotic cells induced by anti-Fas antibody resulted in a doubling increase, while the binding of [(18)F]FPDuramycin with necrotic cells induced by three freeze and thaw cycles resulted in a threefold increase. Biodistribution study in mice exhibited its rapid blood and renal clearance and predominant accumulation in liver and spleen over 120 min postinjection. Small-animal PET/CT imaging with [(18)F]FPDuramycin proved to be a successful way to visualize in vivo therapeutic-induced tumor cell death. In summary, [(18)F]FPDuramycin seems to be a potential PET probe candidate for noninvasive visualization of in vivo cell death sites induced by chemotherapy in tumors.

[Clinical effect of stem cell transplantation via hepatic artery in the treatment of type II hyperammonemia: a report on 6 cases].

This study aimed to investigate the clinical effect of transplantation of CD133⁺ peripheral blood stem cells or umbilical cord mesenchymal stem cells via the hepatic artery in children with type II hyperammonemia and its possible action mechanism. Umbilical cord mesenchymal stem cells were obtained by collecting cord blood (100-150 mL) from healthy fetuses and separating stem cell suspension (5 mL) from the cord blood by hydroxyethyl starch sedimentation. CD133⁺ peripheral blood stem cells were obtained by mobilizing peripheral blood from the fathers of sick children using recombinant human granulocyte colony-stimulating factor for 5 days, collecting mononuclear cells (120 mL), and separating out CD133⁺ cells by sorting. With catheterization and percutaneous puncture, the obtained stem cells were slowly injected into the liver of sick children via the hepatic artery. The changes in clinical symptoms and laboratory indices such as blood ammonia, liver function, and arginine and citrulline concentrations were observed. After stem cell transplantation via the hepatic artery, the 6 children showed significantly decreased blood ammonia levels, and their blood ammonia levels slowly increased 1 to 2 weeks later, but remained below 100 µmol/L, and changes in glutamic-pyruvic transaminase levels were similar to blood ammonia. Plasma citrulline and arginine concentrations increased significantly after transplantation and the increase in citrulline level exceeded the increase in arginine level. An 8 months follow-up visit for one typical patient showed that the weight and height increased after transplantation and sleep was improved without night crying. The child could actively gaze at interesting objects instead of responding indifferently and started to say simple words. With regard to fine motor skills, the child could pinch things with the thumb and middle finger instead of displaying a lack of hand-eye coordination and progress was also made in gross motor skills. Gesell test showed that the child made progress for an average of 3.82 months in all areas. It was concluded that after stem cell transplantation, children with type II hyperammonemia have decreased blood ammonia levels, stable and improved liver function and steadily increased plasma citrulline and arginine concentrations. They display a progressive trend in such aspects as movement, language and environmental adaptability. It is hypothesized that stem cell transplantation via the hepatic artery partially or totally activates, or provides supplementary ornithine carbamoyl transferase, so that plasma citrulline and arginine concentrations increase and urea cycle disorder can be corrected to some extent.

[Transplantation of human neural precursor cells in the treatment of children with pervasive developmental disorder].

OBJECTIVE: To assess the efficiency and safety of human neural progenitor cells (hNPCs) transplantation in the treatment of pervasive developmental disorder (PDD) in children. METHODS: Twenty-two children with PDD were treated, including 13 children with Rett syndrome and 9 children with autism. They accepted hNPCs transplantation voluntarily. hNPCs derived from aborted fetal tissue were injected into the lateral ventricle of the patients under supersonic guidance. All patients were assessed according to the Autism Behavior Checklist before operation, at one and six months post operation, and one year later. RESULTS: No delayed complications resulting from this therapy were observed. The clinical symptoms of 17 patients, including 8 patients with autism and 9 patients with Rett syndrome, improved in varying degrees. The assessment results of the Autism Behavior Checklist for children with autism showed that compared with pre-operative function, social communication scores were significantly reduced at six months after transplantation, and total scores and social communication and language scores were also significantly reduced 1 year after transplantation (P<0.05). CONCLUSIONS: These results suggest that hNPCs transplantation is effective and safe for treatment of PPD in children. It deserves a further study.

Neural stem/progenitor cell transplantation for cortical visual impairment in neonatal brain injured patients.

The purpose of this study was to investigate the clinical efficacy of neural stem/progenitor cell (NS/PC) transplantation to treat severe cortical visual impairment (CVI), a sequela of neonatal brain injury. Fifty-two patients with cerebral injury and CVI were randomly divided into two groups: the treatment group (n = 25, with the median age of 18 months) and the control group (n = 27, with the median age of 19.5 months). The treatment group received intracerebroventricular transplantation of human NS/PCs and rehabilitation training. The control group received rehabilitation only. The visual function was assessed by Holt's method at various time points after transplantation. One in five patients with fundus abnormalities accompanied by blindness regained light perception. The visual functions of 75% of the patients with normal fundus were improved by one level or more in a 2-year follow-up. The median efficacy appeared 60 days posttransplantation. The total effective rate of cell transplantation on visual improvement was 64% (16 patients of 25), among which one blind patient regained light perception, five (31.2%) CVI patients improved by one level, and 10 (62.5%) improved by more than one level. Functional magnetic resonance imaging (fMRI) in a subpopulation of patients showed enhanced signals in the occipital lobe, visual pathway, and apical lobe after transplantation. In the control group, four patients with fundus abnormalities showed no improvement. Nine of 23 CVI patients with normal fundus improved visual function by more than one level. At the 2-year follow-up, no blind patients showed visual improvement. The total effective rate was 33.33% (9 of 27 patients). Among those showing visual improvement in the control group, six patients (66.67%) improved by one level, and three (33.33%) by more than one level. The median efficacy occurred in 365 days. Human NS/PC transplantation is effective to treat patients with severe CVI after neonatal brain injury. Compared with the traditional rehabilitation training, cell transplantation showed not only earlier visual improvement but also higher improvement rates and degrees. This article is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Three-dimensional real-time tracking of nanoparticles at an oil-water interface.

Single-particle tracking with real-time feedback control can be used to study three-dimensional nanoparticle transport dynamics. We apply the method to study the behavior of adsorbed nanoparticles at a silicone oil-water interface in a microemulsion system over a range of particles sizes from 24 nm to 2000 nm. The diffusion coefficient of large particles (>200 nm) scales inversely with particle size, while smaller particles exhibit an unexpected increase in drag force at the interface. The technique can be applied in the future to study three-dimensional dynamics in a range of systems, including complex fluids, gels, biological cells, and geological media.

Effects of neural progenitor cell transplantation in children with severe cerebral palsy.

Cerebral palsy (CP) is a chronic nervous system disease that severely damages the physical and developmental health of children. Traditional treatment brings about only improvement of mild to moderate CP, but severe CP still lacks effective interventions. To explore safety and efficacy of using neural progenitor cells (NPCs) to treat CP in children, we performed NPC transplantation in 45 patients with severe CP by injecting NPCs derived from aborted fetal tissue into the lateral ventricle. Gross motor function measures (GMFM), the Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, and a unified survey questionnaire designed specifically for children with CP were used to evaluate neurological function of the patients. Motor development was significantly accelerated within the first month after cell transplantation, but the rate of improvement gradually slowed to preoperative levels. However, after 1 year, the developmental level in each functional sphere (gross motor, fine motor, and cognition) of the treatment group was significantly higher compared to the control group. No delayed complications of this therapy were noted. These results suggest that NPC transplantation is a safe and effective therapeutic method for treating children with severe CP.