Efficacy and safety assessment of intravenous transplantation of human amnion membrane mesenchymal stem cells in treatment of APP⁺ transgenic mice with Alzheimer's disease

Background: The etiology of Alzheimer's disease is still unclear. Human amnion membrane mesenchymal stem cell intravenous transplantation can promote the learning and memory improvement in APP⁺ transgenic mice of Alzheimer's disease. Objective: To estimate the efficacy and safety of intravenous transplantation of human amnion membrane mesenchymal stem cells in APP⁺ transgenic mice of Alzheimer's disease. Design, time and setting: The cytology in vivo study and animal controlled study were performed at the Department of Bioengineering, Zhengzhou University, College of Basic Medical Sciences, Zhengzhou University, and Henan Institute of Traditional Chinese Medicine from May to December 2008. Materials: A total of 10 clean C57BL/6 APP⁺ transgenic fetal mice were fed in the same cage for breeding, and 200 generation mice were obtained. According to breeding and PCR results, 19 mice aged 11 months were collected and assigned into APP+ control group (n=10), APP⁺ transplantation group (n=10), and APP^- normal group (n=9). Amnion membrane was supplied by the Department of Obstetrics, First Affiliated Hospital, Zhengzhou University. Methods: Human amnion membrane mesenchymal stem cells were isolated in vitro. At the third passage, single cell suspension at 1×10⁹/L was obtained. Mice in the APP⁺ transplantation group were injected with 0.5 mL of human amnion membrane mesenchymal stem cell suspension through caudal vein injection. Mice in the APP⁺ control group were infused with the same volume of saline. Mice in the APP^- normal group were left intact. Main outcome measures: Learning and memory ability in mice were explored by Morris Maze method. The body weight was weighed for three days after transplantation. The transplanted mice were dissected to get the blood and serum. The biochemical indicator of the heart, liver and kidney function and twelve tumor markers were detected to estimate the safety of cells transplantation. Results: At 15 days following transplantation, escaping latency in each group was as follows: APP^- normal group < APP⁺ transplantation group < APP⁺ control group. The escaping latency was significantly shorter in the APP⁺ transplantation group than in the APP⁺ control group (P< 0.05). Compared with pretransplantation, the number of crossing platform quadrant increased in each group at 15 days following transplantation. The time of crossing platform quadrant was significantly longer in the APP⁺ transplantation group. Within 3 weeks after transplantation, no significant difference in the growth tendency of body weight was found in each group (P>0.05). There was no significant difference in biochemical indicators of the heart, liver and kidney function and twelve tumor markers (P>0.05). Conclusion: Intravenous transplantation of human amnion membrane mesenchymal stem cells can significantly improve the learning and memory ability of Alzheimer's disease mice. No death and tumor occurred in mice, and the heart, liver and kidney function is not affected. Thus, the transplantation is safe and feasible.