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| Research article summary (published 29 Apr 2003): |
Engineering of the extracellular matrix: working toward neural stem cell programming and neurorestoration--concept and progress report.
Full Abstract
In the concept of neurorestoration, cellular and structural elements that have been lost are replaced, and their function is restored. Central to this therapeutic strategy is the transplantation of neural progenitor cells such as clonogenically expanded stem cells. Stem cells make decisions regarding fate and patterning in response to external environmental signals. The therapeutic effectiveness of neural stem cells may be facilitated by the ability to manipulate these signals in a temporal and spatially appropriate fashion. Artificial deoxyribonucleic acid and artificial protein technology combines elements of protein engineering, molecular biology, and recombinant deoxyribonucleic acid technology to produce proteins with functional domains derived from naturally occurring proteins and represents a potentially powerful tool to modulate stem cell behavior. To this end, we have developed three artificial extracellular matrix proteins that incorporate the active domain of hJagged1 and hDelta1 into an elastin backbone. hJagged1 and hDelta1 are members of the DSL family of ligands to the Notch receptor, a signaling system that is very important in development and is the strongest known signal to instruct neural progenitor cells to choose glial fates over neuronal fates. The successful cloning of the artificial genes was confirmed by test digestions with appropriate restriction enzymes as well as direct deoxyribonucleic acid sequencing. In addition, we have demonstrated that all three artificial extracellular matrix proteins express at a high level in a prokaryotic host. This report describes the concept and progress in an entirely novel and previously unreported approach to modulate neural stem cell behavior. Its future application could include in vitro processing of stem cells before transplantation, supporting and programming the cells after transplantation, as well as the development of bioactive biomaterials.
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Author information
Author/s: Liu, Charles Y (CY); Apuzzo, Michael L J (ML); Tirrell, David A (DA);
Affiliation: Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. chasliu(-atsign-)cheme.caltech.edu
Grants: R01-HL59987-03 (Agency:United States NHLBI)
Journal and publication information
Publication Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Review
Journal: Neurosurgery (Neurosurgery), published in United States. (Language: eng)
Reference: 2003-May; vol 52 (issue 5) : pp 1154-65; discussion 1165-7
Dates: Created 2003/04/17; Completed 2003/06/25; Revised 2007/11/14;
PMID: 12699561, status: MEDLINE (last retrieval date: 11/6/2008)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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