title: Heparan sulfate enhances the self-renewal and therapeutic potential of mesenchymal stem cells from human adult bone marrow.
abstract: Insufficient cell number hampers therapies utilizing adult human mesenchymal stem cells (hMSCs) and current ex vivo expansion strategies lead to a loss of multipotentiality. Here we show that supplementation with an embryonic form of heparan sulfate (HS-2) can both increase the initial recovery of hMSCs from bone marrow aspirates and increase their ex vivo expansion by up to 13-fold. HS-2 acts to amplify a subpopulation of hMSCs harboring longer telomeres and increased expression of the MSC surface marker stromal precursor antigen-1. Gene expression profiling revealed that hMSCs cultured in HS-2 possess a distinct signature that reflects their enhanced multipotentiality and improved bone-forming ability when transplanted into critical-sized bone defects. Thus, HS-2 offers a novel means for decreasing the expansion time necessary for obtaining therapeutic numbers of multipotent hMSCs without the addition of exogenous growth factors that compromise stem cell fate.
authors: Laboratory of Stem Cells and Tissue Repair, Institute of Medical Biology, Immunos, A*STAR, Singapore, Singapore.
authors: Torben
authors: T
authors: Helledie
authors: Christian
authors: C
authors: Dombrowski
authors: Bina
authors: B
authors: Rai
authors: Zophia X H
authors: ZX
authors: Lim
authors: Ian Lee Hock
authors: IL
authors: Hin
authors: David A
authors: DA
authors: Rider
authors: Gary S
authors: GS
authors: Stein
authors: Wanjin
authors: W
authors: Hong
authors: Andre J
authors: AJ
authors: van Wijnen
authors: James H
authors: JH
authors: Hui
authors: Victor
authors: V
authors: Nurcombe
authors: Simon M
authors: SM
authors: Cool
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001847:Bone Diseases / Q000628:therapy; D001853:Bone Marrow / Q000378:metabolism*; D001861:Bone Regeneration; D002454:Cell Differentiation; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation; D002470:Cell Survival; D020869:Gene Expression Profiling; D006497:Heparan Sulfate / Q000494:pharmacology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D023421:Models, Animal; D051381:Rats; D011923:Rats, Nude; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006497:Heparan Sulfate