Document Detail


Reconstitution of marrow-derived extracellular matrix ex vivo: a robust culture system for expanding large-scale highly functional human mesenchymal stem cells.
MedLine Citation:
PMID:  19737070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The difficulty in long-term expansion of mesenchymal stem cells (MSCs) using standard culture systems without the loss of their stem cell properties suggests that a critical feature of their microenvironment necessary for retention of stem cell properties is absent in these culture systems. We report here the reconstitution of a native extracellular matrix (ECM) made by human marrow cells ex vivo, which consists of at least collagen types I and III, fibronectin, small leucine-rich proteoglycans such as biglycan and decorin, and major components of basement membrane such as the large molecular weight proteoglycan perlecan and laminin. Expansion of human MSCs on this ECM strongly promoted their proliferation, retained their stem cell properties with a low level of reactive oxygen species (ROS), and substantially increased their response to BMP-2. The quality of the expanded cells following each passage was further tested by an in vivo transplantation assay. The results showed that MSCs expanded on the ECM for multiple passages still retained the same capacity for skeletogenesis. In contrast, the bone formation capacity of cells expanded on plastic was dramatically diminished after 6-7 passages. These findings suggest that the marrow stromal cell-derived ECM is a promising matrix for expanding largescale highly functional MSCs for eventualuse in stem cell-based therapy. Moreover, this system should also be invaluable for establishment of a unique tissue-specific ECM, which will facilitate control of the fate of MSCs for therapeutic applications.
Authors:
Yanlai Lai; Yun Sun; Charles M Skinner; Eugene L Son; Zhongding Lu; Rocky S Tuan; Robert L Jilka; Jian Ling; Xiao-Dong Chen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells and development     Volume:  19     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-16     Completed Date:  2010-10-25     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1095-107     Citation Subset:  IM    
Affiliation:
Department of Restorative Dentistry, Division of Biomaterials, The University of Texas Health Science Center at San Antonio , San Antonio, TX 78229-3900, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / cytology,  physiology*
Bone Morphogenetic Protein 2 / genetics,  metabolism
Cell Culture Techniques / methods*
Cells, Cultured
Extracellular Matrix / chemistry,  metabolism*
Extracellular Matrix Proteins / genetics,  metabolism
Humans
Integrin-Binding Sialoprotein
Mesenchymal Stem Cells / cytology,  physiology*
Microarray Analysis
Osteocalcin / genetics,  metabolism
Reactive Oxygen Species / metabolism
Sialoglycoproteins / genetics,  metabolism
Telomerase / metabolism
Grant Support
ID/Acronym/Agency:
P01AG19316/AG/NIA NIH HHS; P30 AG013319/AG/NIA NIH HHS; P30 CA54174/CA/NCI NIH HHS; R21 AG025466/AG/NIA NIH HHS; ZO1AR41131/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/BMP2 protein, human; 0/Bone Morphogenetic Protein 2; 0/Extracellular Matrix Proteins; 0/IBSP protein, human; 0/Integrin-Binding Sialoprotein; 0/Reactive Oxygen Species; 0/Sialoglycoproteins; 104982-03-8/Osteocalcin; EC 2.7.7.49/Telomerase
Comments/Corrections

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