PURPOSE: In order to address cell dose limitations associated with the use of cord blood hematopoietic stem cell (HSC) transplantation, we explored the effect of bone marrow stroma-derived heparan sulfate (HS) on the ex vivo expansion of HSCs. METHODS: Heparan sulfate was isolated and purified from the conditioned media of human bone marrow stromal cells and used for the expansion of cord blood-derived CD34(+) cells in the presence of a cocktail of cytokines. RESULTS: The number of myeloid lineage-committed progenitor cells was increased at low dosage of HS as illustrated by an increase in the total number of colony-forming cells (CFC) and colonies of erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) precursors. Notably, the stroma-derived HS did not alter the growth of CD34(+) HSCs or negatively affect the levels of various HSC phenotypic markers after expansion. CONCLUSIONS: This study shows that HS secreted into solution by stromal cells has the capacity to support hematopoietic cytokines in the maintenance and expansion of HSCs. The incorporation of stroma-derived HS as a reagent may improve the efficacy of cord blood HSC transplantation by enhancing the number of committed cells and accelerating the rate of engraftment.
PURPOSE: In order to address cell dose limitations associated with the use of cord blood hematopoietic stem cell (HSC) transplantation, we explored the effect of bone marrow stroma-derived heparan sulfate (HS) on the ex vivo expansion of HSCs. METHODS:Heparan sulfate was isolated and purified from the conditioned media of human bone marrow stromal cells and used for the expansion of cord blood-derived CD34(+) cells in the presence of a cocktail of cytokines. RESULTS: The number of myeloid lineage-committed progenitor cells was increased at low dosage of HS as illustrated by an increase in the total number of colony-forming cells (CFC) and colonies of erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) precursors. Notably, the stroma-derived HS did not alter the growth of CD34(+) HSCs or negatively affect the levels of various HSC phenotypic markers after expansion. CONCLUSIONS: This study shows that HS secreted into solution by stromal cells has the capacity to support hematopoietic cytokines in the maintenance and expansion of HSCs. The incorporation of stroma-derived HS as a reagent may improve the efficacy of cord blood HSC transplantation by enhancing the number of committed cells and accelerating the rate of engraftment.
Authors: Jennifer Jaroscak; Kristin Goltry; Alan Smith; Barbara Waters-Pick; Paul L Martin; Timothy A Driscoll; Richard Howrey; Nelson Chao; Judy Douville; Sue Burhop; Pingfu Fu; Joanne Kurtzberg Journal: Blood Date: 2003-02-20 Impact factor: 22.113
Authors: A Peled; I Petit; O Kollet; M Magid; T Ponomaryov; T Byk; A Nagler; H Ben-Hur; A Many; L Shultz; O Lider; R Alon; D Zipori; T Lapidot Journal: Science Date: 1999-02-05 Impact factor: 47.728
Authors: Colleen Delaney; Shelly Heimfeld; Carolyn Brashem-Stein; Howard Voorhies; Ronald L Manger; Irwin D Bernstein Journal: Nat Med Date: 2010-01-17 Impact factor: 53.440
Authors: Elizabeth J Shpall; Ralph Quinones; Roger Giller; Chan Zeng; Anna E Baron; Roy B Jones; Scott I Bearman; Yago Nieto; Brian Freed; Nancy Madinger; Christopher J Hogan; Vicki Slat-Vasquez; Peggy Russell; Betsy Blunk; Deborah Schissel; Elaine Hild; Janet Malcolm; William Ward; Ian K McNiece Journal: Biol Blood Marrow Transplant Date: 2002 Impact factor: 5.742
Authors: Christian Dombrowski; Shu Jun Song; Peiying Chuan; Xinhong Lim; Evelyn Susanto; Amber A Sawyer; Maria A Woodruff; Dietmar W Hutmacher; Victor Nurcombe; Simon M Cool Journal: Stem Cells Dev Date: 2009-05 Impact factor: 3.272
Authors: Ling Ling; Emily T Camilleri; Torben Helledie; Rebekah M Samsonraj; Drew M Titmarsh; Ren Jie Chua; Oliver Dreesen; Christian Dombrowski; David A Rider; Mario Galindo; Ian Lee; Wanjin Hong; James H Hui; Victor Nurcombe; Andre J van Wijnen; Simon M Cool Journal: Gene Date: 2015-10-17 Impact factor: 3.688
Authors: Diah S Bramono; Sadasivam Murali; Bina Rai; Ling Ling; Wei Theng Poh; Zophia Xuehui Lim; Gary S Stein; Victor Nurcombe; Andre J van Wijnen; Simon M Cool Journal: Bone Date: 2011-12-28 Impact factor: 4.398