PMID- 28796260 OWN - NLM STAT- MEDLINE DCOM- 20180430 LR - 20181202 IS - 2041-4889 (Electronic) VI - 8 IP - 8 DP - 2017 Aug 10 TI - Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis. PG - e2996 LID - 10.1038/cddis.2017.316 [doi] AB - Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging brain may be a promising approach for rejuvenating cognitive aging. Here, we sought to study the intervention effects of clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive aging in a murine model of aging. The conventional aging model in mice induced by d-galactose (d-gal) was employed here. Mice received once every two weeks intraperitoneal administration of hUC-MSCs. After 3 months of systematical regulation of hUC-MSCs, the hippocampal-dependent learning and memory ability was effectively improved in aged mice, and the synaptic plasticity was remarkably enhanced in CA1 area of the aged hippocampus; moreover, the neurobiological substrates that could impact on the function of hippocampal circuits were recovered in the aged hippocampus reflecting in: dendritic spine density enhanced, neural sheath and cytoskeleton restored, and postsynaptic density area increased. In addition, the activation of the endogenic neurogenesis which is beneficial to stabilize the neural network in hippocampus was observed after hUC-MSCs transplantation. Furthermore, we demonstrated that beneficial effects of systematical regulation of hUC-MSCs could be mediated by activation of mitogen-activated protein kinase (MAPK)-ERK-CREB signaling pathway in the aged hippocampus. Our study provides the first evidence that hUC-MSCs, which have the capacity of systematically regulating the aging brain, may be a potential intervention for cognitive aging. FAU - Cao, Ning AU - Cao N AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. FAU - Liao, Tuling AU - Liao T AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. FAU - Liu, Jiajing AU - Liu J AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. FAU - Fan, Zeng AU - Fan Z AUID- ORCID: 0000-0002-3033-4920 AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. FAU - Zeng, Quan AU - Zeng Q AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Zhou, Junnian AU - Zhou J AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Pei, Haiyun AU - Pei H AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Xi, Jiafei AU - Xi J AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - He, Lijuan AU - He L AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Chen, Lin AU - Chen L AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Nan, Xue AU - Nan X AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Jia, Yali AU - Jia Y AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Yue, Wen AU - Yue W AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. FAU - Pei, Xuetao AU - Pei X AD - Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China. AD - South China Research Center for Stem Cell and Regenerative Medicine, South China Institute Biomedicine, Guangzhou, China. LA - eng PT - Journal Article DEP - 20170810 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 SB - IM MH - Animals MH - Blotting, Western MH - Cell Differentiation/genetics/physiology MH - Cognitive Aging/*physiology MH - Disease Models, Animal MH - Electrophysiology MH - Humans MH - Immunohistochemistry MH - Male MH - Maze Learning/*physiology MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Electron MH - Neurogenesis/genetics/*physiology MH - Neuronal Plasticity/genetics/*physiology MH - Umbilical Cord/cytology PMC - PMC5596535 COIS- The authors declare no conflict of interest. EDAT- 2017/08/11 06:00 MHDA- 2018/05/01 06:00 PMCR- 2017/08/01 CRDT- 2017/08/11 06:00 PHST- 2017/04/11 00:00 [received] PHST- 2017/05/17 00:00 [revised] PHST- 2017/05/23 00:00 [accepted] PHST- 2017/08/11 06:00 [entrez] PHST- 2017/08/11 06:00 [pubmed] PHST- 2018/05/01 06:00 [medline] PHST- 2017/08/01 00:00 [pmc-release] AID - cddis2017316 [pii] AID - 10.1038/cddis.2017.316 [doi] PST - epublish SO - Cell Death Dis. 2017 Aug 10;8(8):e2996. doi: 10.1038/cddis.2017.316.