PMID- 17651977 OWN - NLM STAT- MEDLINE DCOM- 20071031 LR - 20220409 IS - 0969-9961 (Print) IS - 0969-9961 (Linking) VI - 27 IP - 3 DP - 2007 Sep TI - Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord-derived stromal cell implanted stroke model. PG - 339-53 AB - Neuroplasticity subsequent to functional angiogenesis is an important goal for cell-based therapy of ischemic neural tissues. At present, the cellular and molecular mechanisms involved are still not well understood. In this study, we isolated mesenchymal stem cells (MSCs) from Wharton's jelly (WJ) to obtain clonally expanded human umbilical cord-derived mesenchymal stem cells (HUCMSCs) with multilineage differentiation potential. Experimental rats receiving intracerebral HUCMSC transplantation showed significantly improved neurological function compared to vehicle-treated control rats. Cortical neuronal activity, as evaluated by proton MR spectroscopy (1H-MRS), also increased considerably in the transplantation group. Transplanted HUCMSCs migrated towards the ischemic boundary zone and differentiated into glial, neuronal, doublecortin+, CXCR4+, and vascular endothelial cells to enhance neuroplasticity in the ischemic brain. In addition, HUCMSC transplantation promoted the formation of new vessels to increase local cortical blood flow in the ischemic hemisphere. Modulation by stem cell-derived macrophage/microglial interactions, and increased beta1-integrin expression, might enhance this angiogenic architecture within the ischemic brain. Inhibition of beta1-integrin expression blocked local angiogenesis and reduced recovery from neurological deficit. In addition, significantly increased modulation of neurotrophic factor expression was also found in the HUCMSC transplantation group. In summary, regulation of beta1-integrin expression plays a critical role in the plasticity of the ischemic brain after the implantation of HUCMSCs. FAU - Ding, Dah-Ching AU - Ding DC AD - Graduate Institute of Medical Science, School of Medicine, Buddhist Tzu Chi General Hospital, Tzu-Chi University, Department of Obstetrics and Gynecology, Hualien, Taiwan 970. FAU - Shyu, Woei-Cherng AU - Shyu WC FAU - Chiang, Ming-Fu AU - Chiang MF FAU - Lin, Shinn-Zong AU - Lin SZ FAU - Chang, Ying-Chen AU - Chang YC FAU - Wang, Hsiao-Jung AU - Wang HJ FAU - Su, Ching-Yuan AU - Su CY FAU - Li, Hung AU - Li H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070618 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (Dcx protein, rat) RN - 0 (Doublecortin Protein) RN - 0 (Integrin beta1) SB - IM MH - Animals MH - Blotting, Western MH - Brain/blood supply MH - Brain Ischemia/*therapy MH - Cell Differentiation/physiology MH - Cell Movement/physiology MH - Doublecortin Protein MH - Humans MH - Immunohistochemistry MH - Immunophenotyping MH - In Situ Hybridization, Fluorescence MH - Integrin beta1/*biosynthesis MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology MH - Microscopy, Confocal MH - *Neovascularization, Physiologic MH - Neuronal Plasticity/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stroke/*therapy MH - Stromal Cells/transplantation MH - Umbilical Cord/cytology MH - Up-Regulation EDAT- 2007/07/27 09:00 MHDA- 2007/11/01 09:00 CRDT- 2007/07/27 09:00 PHST- 2007/03/07 00:00 [received] PHST- 2007/05/03 00:00 [revised] PHST- 2007/06/04 00:00 [accepted] PHST- 2007/07/27 09:00 [pubmed] PHST- 2007/11/01 09:00 [medline] PHST- 2007/07/27 09:00 [entrez] AID - S0969-9961(07)00114-3 [pii] AID - 10.1016/j.nbd.2007.06.010 [doi] PST - ppublish SO - Neurobiol Dis. 2007 Sep;27(3):339-53. doi: 10.1016/j.nbd.2007.06.010. Epub 2007 Jun 18.