TGFbeta1 limits the expansion of the osteoprogenitor fraction in cultures of human bone marrow stromal cells

Currently, there is considerable interest in the possibility of using cultured human bone marrow stromal cells (BMSCs) for skeletal tissue engineering. However, the factors that regulate their ex vivo expansion and promote their osteogenic maturation remain poorly defined. Using BMSCs obtained from...

Full description

Saved in:
Bibliographic Details
Published in:Cell and tissue research 2003-02, Vol.311 (2), p.187-198
Main Authors: Walsh, Susan, Jefferiss, Carolyn, Stewart, Karina, Beresford, Jon N
Format: Article
Language:English
Subjects:
Adult
Aged
Alkaline Phosphatase - metabolism
Bone Marrow Cells - cytology
Bone Marrow Cells - drug effects
Bone Marrow Cells - ultrastructure
Cell Culture Techniques - methods
Cell Division - drug effects
Cell Separation - methods
Cell Size
Cells, Cultured
Colony-Forming Units Assay
Female
Flow Cytometry
Humans
Male
Middle Aged
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - ultrastructure
Stromal Cells - cytology
Stromal Cells - drug effects
Stromal Cells - ultrastructure
Transforming Growth Factor beta - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Currently, there is considerable interest in the possibility of using cultured human bone marrow stromal cells (BMSCs) for skeletal tissue engineering. However, the factors that regulate their ex vivo expansion and promote their osteogenic maturation remain poorly defined. Using BMSCs obtained from a large cohort of adult donors, the effects of transforming growth factor (TGF)beta1 on these processes have been determined. BMSCs were found to express TGFbeta receptors (TbetaRs) I, II, III (betaglycan) and CD105/endoglin. The expression of TbetaRs I and II, but not TbetaR III or endoglin, was linked to the cells' state of maturation. Treatment with TGFbeta increased the colony-forming efficiency (CFE) of marrow cell suspensions but reduced the median diameter of the colonies that formed and the number of cells harvested at the end of primary culture. Treatment with TGFbeta also resulted in a significant downregulation in the expression of the developmental markers alkaline phosphatase (AP) and STRO-1. The reduction in AP was due to a decrease in the absolute number of cells expressing this enzyme and in the level (sites/cell) at which it was expressed. Overall, the changes in the expression of STRO-1 and AP are consistent with TGFbeta acting to decrease the size of the osteoprogenitor fraction, and hence the potential clinical utility of the cultured cell population.
ISSN:0302-766X
1432-0878