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Transplantation of Enteric Neural Stem/Progenitor Cells into the Irradiated Young Mouse Hippocampus.

Journal article
Authors Ahmed M Osman
Kai Zhou
Changlian Zhu
Klas Blomgren
Published in Cell transplantation
Volume 23
Issue 12
Pages 1657-1671
ISSN 1555-3892
Publication year 2014
Published at Institute of Neuroscience and Physiology
Institute of Clinical Sciences, Department of Pediatrics
Pages 1657-1671
Language en
Links dx.doi.org/10.3727/096368913X674648
Subject categories Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Abstract

Radiotherapy is an effective treatment for brain tumors, but often results in cognitive deficits in survivors. Transplantation of embryonic or brain-derived neural stem/progenitor cells (BNSPCs) ameliorated cognitive impairment after irradiation (IR) in animal models. However, such an approach in patients requires a clinically relevant source of cells. We show for the first time the utilization of enteric neural stem/progenitor cells (ENSPCs) from the postnatal intestinal wall as a source of autologous cells for brain repair after injury caused byIR. Cells were isolated from the intestinal wall and propagated in vitro for one week. Differentiation assays showed that ENSPCs are multipotent and generated neurons, astrocytes and myofibroblasts.To investigate whether ENSPCs can be used in vivo, postnatal day 9 mice were subjected to a singlemoderate irradiation dose (6 or 8 Gy). Twelve days later, mice received an intrahippocampal injection of syngeneic ENSPCs. Four weeks after transplantation, 0.5% and 1% of grafted ENSPCs were detected in the dentate gyrus of sham and irradiated animals, respectively, and only 0.1%were detected after 16 weeks. Grafted ENSPCs remained undifferentiated, but failed to restore IR-induced loss of BNSPCs and the subsequent impaired growth of the dentate gyrus. We observed microglia activation, astrogliosis and loss of granule neurons associated with grafted ENSPC clusters. Transplantation of ENSPCs did not ameliorate IR-induced impaired learning and memory. In summary, while autologous ENSPC grafting to the brain worked technically, even in the absence of immunosuppression, the protocols need to be modified to improve survival and integration.

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