2011
DOI: 10.1016/j.stem.2011.06.003
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Ex Vivo Expanded Hematopoietic Stem Cells Overcome the MHC Barrier in Allogeneic Transplantation

Abstract: Summary The lack of understanding of the interplay between hematopoietic stem cells (HSCs) and the immune system has severely hampered the stem cell research and practice of transplantation. Major problems for allogeneic transplantation include low levels of donor engraftment and high risks of graft-versus-host disease (GVHD). Transplantation of purified allogeneic HSCs diminishes the risk of GVHD, but results in decreased engraftment. Here we show that ex vivo expanded mouse HSCs efficiently overcame the majo… Show more

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Cited by 57 publications
(74 citation statements)
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“…Alternatively, supraphysiological concentrations of ANGPTL8 may induce b-cell proliferation, but this would be expected to cause hypertriglyceridemia. Other family members, including ANGPTL3, have been shown to promote proliferation of hematopoietic stem cells (32)(33)(34).…”
Section: Discussionmentioning
confidence: 99%
“…Alternatively, supraphysiological concentrations of ANGPTL8 may induce b-cell proliferation, but this would be expected to cause hypertriglyceridemia. Other family members, including ANGPTL3, have been shown to promote proliferation of hematopoietic stem cells (32)(33)(34).…”
Section: Discussionmentioning
confidence: 99%
“…Technologies) supplemented with 10 μg/ml heparin (Sigma-Aldrich), 10 ng/ml mouse or 50 ng/ml human SCF (Peprotech), and 20 ng/ml mouse or 10 ng/ml human TPO (Peprotech), with or without serumfree ANGPTL2-or ANGPTL3-conditioned medium or their purified exosomes, as previously described (60 StemSpan serum-free medium supplemented with mouse or human SCF, IL-3, IL-6 (Peprotech), and FLT3 ligand (for human AML cells only, Peprotech) with or without serum-free ANGPTL2-or ANGPTL3-conditioned medium or their purified exosomes. In some cases, exosomes purified from human plasma were added to the culture medium.…”
Section: Methodsmentioning
confidence: 99%
“…We showed that ex vivo-expanded mouse HSCs dramatically upregulated the cell surface immune inhibitor programmed death-ligand 1 (PD-L1, also known as B7-H1 or CD274) and efficiently repopulated allogeneic recipient mice by overcoming the major histocompatibility complex barrier [73]. In this study, a 40-fold increase of the allograft ability of ex vivo expanded HSCs was achieved relative to the uncultured control after 8 d of culture.…”
Section: Expansion Of Mouse Hscsmentioning
confidence: 71%
“…The abilities of many cytokines to support hematopoietic progenitors to form colonies in vitro provided important insights into expansion of functional primitive long-term (LT-) HSCs that are measured by in vivo repopulating activity [49]. In the last two decades, a number of secreted/extracellular proteins/chemicals have been demonstrated to support ex vivo expansion of mouse HSCs, including stem cell factor (SCF) [50], thrombopoietin (TPO) [51][52][53], Notch ligands [54,55], Wnt ligands [56][57][58][59], fibroblast growth factor 1 (FGF-1) [60,61], bone morphogenetic proteins (BMPs) [62], Hedgehogs [62][63][64], prostaglandin E2 (PGE2) [65], interleukin 10 (IL-10) [66], insulin-like growth factor 2 (IGF-2) [67,68], IGF binding protein 2 (IGFBP2) [69,70], several angiopoietin-like proteins (Angptls) [71][72][73][74], and pleiotrophin [75]. Conditional derivatives of certain growth factor receptors have also been used to support HSC expansion in culture [76,77].…”
Section: Expansion Of Mouse Hscsmentioning
confidence: 99%
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