PMID- 25586060 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220408 IS - 1559-1182 (Electronic) IS - 0893-7648 (Print) IS - 0893-7648 (Linking) VI - 53 IP - 2 DP - 2016 Mar TI - Designer Self-Assemble Peptides Maximize the Therapeutic Benefits of Neural Stem Cell Transplantation for Alzheimer's Disease via Enhancing Neuron Differentiation and Paracrine Action. PG - 1108-1123 LID - 10.1007/s12035-014-9069-y [doi] AB - The neuropathological hallmarks of Alzheimer's disease (AD) include the presence of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques and neuronal loss. Neural stem cell (NSC) is being scrutinized as a promising cell replacement therapy for various neurodegenerative diseases. However, the unfavorable niche at the site of degenerative disease is hostile to the survival and differentiation of transplanted cells. Here, we undertook in vitro and in vivo works to examine whether a designer self-assemble peptide (DSP), which contains one functional domain Tyr-Ile-Gly-Ser-Arg (YIGSR) derived from laminin, promotes the survival and neuronal differentiation of NSC and behavioral improvement. We found that DSP could undergo spontaneous assembly into well-ordered nanofibers, and it not only facilitated the cell viability in normal culture condition, but also decreased the number of apoptotic cells induced by Abeta in vitro. NSC seeded in DSP showed much more neuronal differentiation than that seeded in self-assemble peptide (SP) or alone. In the AD model, NSC transplantation in DSP-treated AD rats demonstrated much more obvious cognitive rescue with restoration of learning/memory function compared with NSC transplantation in SP, NSC alone, or DSP alone treated ones. Interestingly, DSP enhanced the survival and neuronal differentiation of transplanted NSC. Apoptosis levels in the CA1 region and Abeta level in the hippocampus were significantly decreased in the group of NSC transplantation in DSP. Moreover, synaptic function, indicated by the expression of pre-synaptic protein synapsin-1, was restored and the secretion of anti-inflammatory and neurotrophic factors were increased, such as IL-10, brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulin-like growth factor 1 (IGF-1), while the expression of pro-inflammatory factors were decreased, such as TNF-alpha and IL-1beta. These data firstly unveiled that the biomaterial DSP can maximize the therapeutic benefits of NSC transplantation for AD through improving the survival and differentiation of transplanted stem cells and promoting the effects of neuroprotection, anti-neuroinflammatory and paracrine action. Our results may have important clinical implications for the design of future NSC-based strategies using the biomaterials for various neurodegenerative diseases including AD. FAU - Cui, Guo-Hong AU - Cui GH AD - Department of Neurology, Shanghai No. 9 People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China. AD - Department of Neurology, Shanghai No. 6 People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200233, China. FAU - Shao, Shui-Jin AU - Shao SJ AD - Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. FAU - Yang, Jia-Jun AU - Yang JJ AD - Department of Neurology, Shanghai No. 6 People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200233, China. FAU - Liu, Jian-Ren AU - Liu JR AD - Department of Neurology, Shanghai No. 9 People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China. liujr021@vip.163.com. FAU - Guo, Hai-Dong AU - Guo HD AD - Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. hdguo8@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150114 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Amyloid beta-Peptides) RN - 0 (Cytokines) RN - 0 (Nerve Growth Factors) RN - 0 (Peptides) RN - 0 (RNA, Messenger) SB - IM MH - Alzheimer Disease/complications/pathology/physiopathology/*therapy MH - Amino Acid Sequence MH - Amyloid beta-Peptides/toxicity MH - Animals MH - Apoptosis/drug effects MH - Behavior, Animal/drug effects MH - Cell Differentiation/*drug effects MH - Cell Survival/drug effects MH - Cytokines/metabolism MH - Inflammation/metabolism/pathology MH - Male MH - Memory Disorders/complications/physiopathology/therapy MH - Microscopy, Atomic Force MH - Molecular Sequence Data MH - Nerve Growth Factors/metabolism MH - Neural Stem Cells/cytology/drug effects/*transplantation MH - Neurons/drug effects/*pathology MH - Paracrine Communication/*drug effects MH - Peptides/chemistry/pharmacology/*therapeutic use MH - RNA, Messenger/genetics/metabolism MH - Rats, Sprague-Dawley MH - Recovery of Function/drug effects MH - *Stem Cell Transplantation MH - Synapses/drug effects/metabolism PMC - PMC4752586 OTO - NOTNLM OT - Alzheimer's disease OT - Differentiation OT - Neural stem cell OT - Self-assembling peptide OT - Transplantation EDAT- 2015/01/15 06:00 MHDA- 2016/12/15 06:00 PMCR- 2015/01/14 CRDT- 2015/01/15 06:00 PHST- 2014/10/03 00:00 [received] PHST- 2014/12/29 00:00 [accepted] PHST- 2015/01/15 06:00 [entrez] PHST- 2015/01/15 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2015/01/14 00:00 [pmc-release] AID - 10.1007/s12035-014-9069-y [pii] AID - 9069 [pii] AID - 10.1007/s12035-014-9069-y [doi] PST - ppublish SO - Mol Neurobiol. 2016 Mar;53(2):1108-1123. doi: 10.1007/s12035-014-9069-y. Epub 2015 Jan 14.