|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, 15 September 2005, Vol. 106, No. 6, pp. 1956-1964. Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2005-02-0657.
HEMATOPOIESIS Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cellsFrom the Hematology/Oncology Section, Veterans Affairs Medical Center; the Stem Cell Institute, the Pediatric Hematology-Oncology and Blood and Marrow Transplantation Program, the Department of Genetics, Cell Biology and Development, the Department of Pediatrics, and the Hematology-Oncology-Transplantation Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN; and the Chinese Academy of Medical Sciences and State Key Laboratory of Experimental Hematology, Beijing, China.
In mucopolysaccharidosis-I (MPS-I),
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
-L-iduronidase deficiency leads to progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan (GAG) accumulation. The functional consequences of these accumulated molecules are unknown. HS critically influences tissue morphogenesis by binding to and modulating the activity of several cytokines (eg, fibroblast growth factors [FGFs]) involved in developmental patterning. We recently isolated a multipotent progenitor cell from postnatal human bone marrow, which differentiates into cells of all 3 embryonic lineages. The availability of multipotent progenitor cells from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a unique opportunity to directly examine the functional effects of abnormal HS on cytokine-mediated stem-cell proliferation and survival. We demonstrate here that abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical FGF-2–FGFR1-HS interactions, resulting in defective FGF-2–induced proliferation and survival of Hurler multipotent progenitor cells. Both the mitogenic and survival-promoting activities of FGF-2 were restored by substitution of Hurler HS by normal HS. This perturbation of critical HS–cytokine receptor interactions may represent a mechanism by which accumulated HS contributes to the developmental pathophysiology of Hurler syndrome. Similar mechanisms may operate in the pathogenesis of other diseases where structurally abnormal GAGs accumulate. 
