PMID- 20525429 OWN - NLM STAT- MEDLINE DCOM- 20110412 LR - 20181201 IS - 1555-3892 (Electronic) IS - 0963-6897 (Linking) VI - 19 IP - 10 DP - 2010 TI - Nonsenescent Hsp27-upregulated MSCs implantation promotes neuroplasticity in stroke model. PG - 1261-79 LID - 10.3727/096368910X507204 [doi] AB - Cellular senescence induces changes in cellular physiology, morphology, proliferative capacity, and gene expression. Stem cell senescence might be one of the major issues of limited efficacy of stem cell transplantation. In this study, we demonstrated that implantation of human umbilical cord mesenchymal stem cells (hUCMSCs) cultured in human umbilical cord serum (hUCS) significantly enhanced neuroplasticity and angiogenesis in stroke and ischemic limb models. Immunophenotypic analysis indicated that hUCMSCs cultured in hUCS had more small and rapidly self-renewing cells than those expanded in FCS. The main cause of greater senescence in FCS-cultured cells was increased generation of reactive oxygen species (ROS). Proteome profiling showed significantly more senescence-associated vimentin in FCS-cultured hUCMSCs than in hUCS-cultured hUCMSCs. In contrast, there was significant upregulation of heat shock protein 27 (Hsp27) in the hUCS-cultured hUCMSCs. By gene targeting, we found that overexpression of Hsp27 may downregulate vimentin expression through inhibition of the nuclear translocation of p65 (NF-kappaB signaling). Thus, an interaction between Hsp27 and vimentin may modulate the degree of senescence in hUCS- and FCS-cultured hUCMSCs. In summary, hUCMSCs exhibiting senescence are detrimental to cell engraftment and differentiation in animal models via activation of NF-kappaB pathway. Human stem cells incubated in hUCS might reduce the senescent process through upregulation of Hsp27 to increase implantation efficiency. FAU - Liu, Shih-Ping AU - Liu SP AD - Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan. FAU - Ding, Dah-Ching AU - Ding DC FAU - Wang, Hsiao-Jung AU - Wang HJ FAU - Su, Ching-Yuan AU - Su CY FAU - Lin, Shinn-Zong AU - Lin SZ FAU - Li, Hung AU - Li H FAU - Shyu, Woei-Cherng AU - Shyu WC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100603 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (HSP27 Heat-Shock Proteins) RN - 0 (Proteome) RN - 0 (Reactive Oxygen Species) RN - 0 (Transcription Factor RelA) RN - 0 (Vimentin) SB - IM MH - Animals MH - Cell Culture Techniques MH - Cells, Cultured MH - Disease Models, Animal MH - Fetal Blood/physiology MH - HSP27 Heat-Shock Proteins/*metabolism MH - Humans MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - *Neuronal Plasticity MH - Phenotype MH - Proteome/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Stroke/*therapy MH - Transcription Factor RelA/metabolism MH - Umbilical Cord/cytology MH - Up-Regulation MH - Vimentin/metabolism EDAT- 2010/06/08 06:00 MHDA- 2011/04/13 06:00 CRDT- 2010/06/08 06:00 PHST- 2010/06/08 06:00 [entrez] PHST- 2010/06/08 06:00 [pubmed] PHST- 2011/04/13 06:00 [medline] AID - ct0034liu [pii] AID - 10.3727/096368910X507204 [doi] PST - ppublish SO - Cell Transplant. 2010;19(10):1261-79. doi: 10.3727/096368910X507204. Epub 2010 Jun 3.