Evaluation of APP695 Transgenic Mice Bone Marrow Mesenchymal Stem Cells Neural Differentiation for Transplantation.
OBJECTIVE
Even though there is a therapeutic potential to treat Alzheimer's disease (AD) with neural cell replenishment and replacement, immunological rejections of stem cell transplantation remain a challenging risk. Autologous stem cells from AD patients however may prove to be a promising candidate. Therefore, we studied the neuronal differentiation efficiency of bone marrow mesenchymal stem cells (MSCs) from APP695 transgenic mice, which share features of human AD.


METHODS
Cultured MSCs from APP695 transgenic mice are used; neuronal differentiation was assessed by immunocytochemistry and Western blot. Correlation with Notch signaling was examined. Autophage flux was assessed by western blot analysis.


RESULTS
MSCs from APP695 mice have higher neuronal differentiation efficiency than MSCs from wild type mice (WT MSCs). The expression of Notch-1 signaling decreased during the differentiation process. However, autophagy flux, which is essential for neuronal cell survival and neuronal function, was impaired in the neuronally differentiated counterparts of APP695 MSCs (APP695 MSCs-n).


CONCLUSIONS
These results suggested autologous MSCs of APP690 mice may not be a good candidate for cell transplantation.
Department of Neurology, The Fifth People's Hospital of Chongqing, Chongqing 400062, China.
Qian
Q
Li
Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
Yanjie
Y
Jia
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
John
J
Zhang
Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
Jun
J
Yang
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019943:Amino Acid Substitution; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D020125:Mutation, Missense; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor