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Artificial Niches for Human Adult Neural Stem Cells: Possibility for Autologous Transplantation Therapy

Liu, Charles Y. and Westerlund, Ulf and Svensson, Mikael and Moe, Morten C. and Varghese, Mercy and Berg-Johnsen, Jon and Apuzzo, Michael L.J. and Tirrell, David A. and Langmoen, Iver A. (2003) Artificial Niches for Human Adult Neural Stem Cells: Possibility for Autologous Transplantation Therapy. Journal of Hematotherapy & Stem Cell Research, 12 (6). pp. 689-699. ISSN 1525-8165. doi:10.1089/15258160360732713.

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Cellular transplantation therapy is thought to play a central role in the concept of restorative neurosurgery, which aims to restore function to the damaged nervous system. Stem cells represent a potentially renewable source of transplantable cells. However, control of the behavior of these cells, both in the process of clonogenic expansion and post-transplantation, represents formidable challenges. Stem cell behavior is thought to be directed by extracellular signals in their in vivo niches, many of which are protein or peptide based. As only one example, activation of Notch plays an important role in normal development and is the strongest known signal for stem cells to choose glial over neuronal fates. Therefore, artificial extracellular matrix proteins represent a potentially powerful tool to custom design artificial niches to strategically control stem cell behavior. We have developed a family of aECM proteins that incorporate the active domains of the DSL ligands to the Notch receptor into an elastin-based backbone. The development of our DSL-elastin artificial proteins demonstrates the design strategy and methodology for the production of bioactive artificial extracellular matrix proteins aimed at modulating stem cell behavior, and this method can be used to design other bioactive aECM proteins. In addition, we have developed a method for the isolation and characterization of adult human neural stem cells from periventricular tissue harvested from living patients. This paper reviews cellular transplantation therapy from the clinical perspective and summarizes ongoing work aimed at exploring the intriguing possibility of autologous transplantation, whereby neural stem cells can be harvested from adult patients, expanded or modified in vitro in artificial niches, and retransplanted into the original patient.

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URLURL TypeDescription CentralAbstract
Tirrell, David A.0000-0003-3175-4596
Additional Information:© Mary Ann Liebert, Inc. 2003 Received September 30,2003; accepted October 24, 2003. The authors are generously supported by the Swedish Research Council, the Norwegian Foundation for Health and Rehabilitation, National Institutes of Health, National Science Foundation, CNS Margot Anderson Foundation, and the Baxter Family Foundation.
Funding AgencyGrant Number
Swedish Research CouncilUNSPECIFIED
Norwegian Foundation for Health and RehabilitationUNSPECIFIED
CNS Margot Anderson FoundationUNSPECIFIED
Baxter Family FoundationUNSPECIFIED
Issue or Number:6
Record Number:CaltechAUTHORS:20150202-100311553
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Official Citation:Charles Y. Liu, Ulf Westerlund, Mikael Svensson, Morten C. Moe, Mercy Varghese, Jon Berg-Johnsen, Michael L.J. Apuzzo, David A. Tirrell, and Iver A. Langmoen. Journal of Hematotherapy & Stem Cell Research. December 2003, 12(6): 689-699. doi:10.1089/15258160360732713.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53310
Deposited By: Anne Hormann
Deposited On:04 Feb 2015 23:37
Last Modified:10 Nov 2021 20:00

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