Advanced

Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain.

Darsalia, Vladimer LU ; Allison, Susan; Cusulin, Carlo LU ; Monni, Emanuela LU ; Kuzdas, Daniela; Kallur, Therese; Lindvall, Olle LU and Kokaia, Zaal LU (2011) In Journal of Cerebral Blood Flow and Metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Jul 1. p.235-242
Abstract
Neural stem cells (NSCs) derived from human fetal striatum and transplanted as neurospheres survive in stroke-damaged striatum, migrate from the implantation site, and differentiate into mature neurons. Here, we investigated how various steps of neurogenesis are affected by intrastriatal transplantation of human NSCs at different time points after stroke and with different numbers of cells in each implant. Rats were subjected to middle cerebral artery occlusion and then received intrastriatal transplants of NSCs. Transplantation shortly after stroke (48 hours) resulted in better cell survival than did transplantation 6 weeks after stroke, but the delayed transplantation did not influence the magnitude of migration, neuronal... (More)
Neural stem cells (NSCs) derived from human fetal striatum and transplanted as neurospheres survive in stroke-damaged striatum, migrate from the implantation site, and differentiate into mature neurons. Here, we investigated how various steps of neurogenesis are affected by intrastriatal transplantation of human NSCs at different time points after stroke and with different numbers of cells in each implant. Rats were subjected to middle cerebral artery occlusion and then received intrastriatal transplants of NSCs. Transplantation shortly after stroke (48 hours) resulted in better cell survival than did transplantation 6 weeks after stroke, but the delayed transplantation did not influence the magnitude of migration, neuronal differentiation, and cell proliferation in the grafts. Transplanting greater numbers of grafted NSCs did not result in a greater number of surviving cells or increased neuronal differentiation. A substantial number of activated microglia was observed at 48 hours after the insult in the injured striatum, but reached maximum levels 1 to 6 weeks after stroke. Our findings show that the best survival of grafted human NSCs in stroke-damaged brain requires optimum numbers of cells to be transplanted in the early poststroke phase, before the inflammatory response is established. These findings, therefore, have direct clinical implications.Journal of Cerebral Blood Flow & Metabolism advance online publication, 9 June 2010; doi:10.1038/jcbfm.2010.81. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cerebral Blood Flow and Metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
volume
Jul 1
pages
235 - 242
publisher
Nature Publishing Group
external identifiers
  • WOS:000285870700025
  • PMID:20531461
  • Scopus:78650860359
ISSN
1559-7016
DOI
10.1038/jcbfm.2010.81
language
English
LU publication?
yes
id
6d2269ad-dd2a-4e3f-afec-8d2975c59713 (old id 1626267)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20531461?dopt=Abstract
date added to LUP
2010-07-05 10:23:12
date last changed
2016-11-27 04:28:30
@misc{6d2269ad-dd2a-4e3f-afec-8d2975c59713,
  abstract     = {Neural stem cells (NSCs) derived from human fetal striatum and transplanted as neurospheres survive in stroke-damaged striatum, migrate from the implantation site, and differentiate into mature neurons. Here, we investigated how various steps of neurogenesis are affected by intrastriatal transplantation of human NSCs at different time points after stroke and with different numbers of cells in each implant. Rats were subjected to middle cerebral artery occlusion and then received intrastriatal transplants of NSCs. Transplantation shortly after stroke (48 hours) resulted in better cell survival than did transplantation 6 weeks after stroke, but the delayed transplantation did not influence the magnitude of migration, neuronal differentiation, and cell proliferation in the grafts. Transplanting greater numbers of grafted NSCs did not result in a greater number of surviving cells or increased neuronal differentiation. A substantial number of activated microglia was observed at 48 hours after the insult in the injured striatum, but reached maximum levels 1 to 6 weeks after stroke. Our findings show that the best survival of grafted human NSCs in stroke-damaged brain requires optimum numbers of cells to be transplanted in the early poststroke phase, before the inflammatory response is established. These findings, therefore, have direct clinical implications.Journal of Cerebral Blood Flow & Metabolism advance online publication, 9 June 2010; doi:10.1038/jcbfm.2010.81.},
  author       = {Darsalia, Vladimer and Allison, Susan and Cusulin, Carlo and Monni, Emanuela and Kuzdas, Daniela and Kallur, Therese and Lindvall, Olle and Kokaia, Zaal},
  issn         = {1559-7016},
  language     = {eng},
  pages        = {235--242},
  publisher    = {ARRAY(0x8c318d8)},
  series       = {Journal of Cerebral Blood Flow and Metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
  title        = {Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain.},
  url          = {http://dx.doi.org/10.1038/jcbfm.2010.81},
  volume       = {Jul 1},
  year         = {2011},
}