ArticleStem cell research & therapy2014
Low-dose insulin-like growth factor binding proteins 1 and 2 and angiopoietin-like protein 3 coordinately stimulate ex vivo expansion of human umbilical cord blood hematopoietic stem cells as assayed in NOD/SCID gamma null mice.
Article in Stem cell research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Impact of targeting the platelet-activating factor and its receptor in cancer treatment.Military Medical Research · 2025Review
- Ex Vivo Expansion and Homing of Human Cord Blood Hematopoietic Stem Cells.Advances in experimental medicine and biology · 2023Article
- Human umbilical cord mesenchymal stem cells in diabetes mellitus and its complications: applications and research advances.International journal of medical sciences · 2023Review
- Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells.Cancers · 2022Review
- Article
- Platelet-activating factor induces the stemness of ovarian cancer cells via the PAF/PAFR signaling pathway.American journal of translational research · 2020Article
- Effect of combined sublethal X-ray irradiation and cyclosporine A treatment in NOD scid gamma (NSG) mice.Experimental animals · 2019Article
- 3D models of the hematopoietic stem cell niche under steady-state and active conditions.Scientific reports · 2017Article
- Spheroid Coculture of Hematopoietic Stem/Progenitor Cells and Monolayer Expanded Mesenchymal Stem/Stromal Cells in Polydimethylsiloxane Microwells Modestly Improves In Vitro Hematopoietic Stem/Progenitor Cell Expansion.Tissue engineering. Part C, Methods · 2017Article
- Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates.Stem cells translational medicine · 2017Article
- Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties.Stem cells translational medicine · 2017Article
- An Overview on Human Umbilical Cord Blood Stem Cell-Based Alternative In Vitro Models for Developmental Neurotoxicity Assessment.Molecular neurobiology · 2016Review
- Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling.eLife · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionInsulin-like growth factors (IGFs), IGF binding proteins (IGFBPs) and angiopoietin-like proteins (ANGPTLs) can enhance the ex vivo expansion of hematopoietic stem cells (HSCs) when used with a standard cytokine cocktail of stem cell factor (SCF), thrombopoietin (TPO) and FLT3 ligand (FL). In order to determine the optimal dose and combination of IGFs, IGFBPs and ANGPTLs, serial dilution and full permutation of IGFBP1, IGFBP2, IGF2 and ANGPTL3 were applied on a cryopreserved umbilical cord blood mononuclear cell (UCB-MNC) ex vivo expansion system.
methodsIn this system, 4 × 105 cells/ml of UCB-MNCs were inoculated in serum-free Stemspan® medium (Stemcell technologies, vancouver, BC, Canada) supplied with standard basal cytokine combination of 100 ng/ml SCF, 50 ng/ml FL and 100 ng/ml TPO and supported by a bone marrow mesenchymal stromal cell layer.
resultsParadoxically, experiment results showed that the highest expansion of CD34+CD38-CD90+ primitive progenitor was stimulated by cytokine combination of SCF + TPO + FL + IGFBP1 + IGFBP2 + ANGPTL3 at a low dose of 15 ng/ml IGFBP1 and 20 ng/ml IGFBP2 and ANGPTL3. This ex vivo expansion was further validated in 8-week-old to 10-week-old nonobese diabetic/severe combined immunodeficiency interleukin 2 gamma chain null (NOD/SCID-IL2Rγ-/-) mice. Limiting dilution assay showed excellent correlation between the HSC ex vivo surface marker of CD34+CD38-CD90+ and the in vivo competitive repopulating unit (CRU) functional assay.
conclusionIGFBP1, IGFBP2, IGF2 and ANGPTL3 can stimulate the expansion of CD34+CD38-CD90+ primitive progenitor at low dose. The optimal combination comprises IGFBP1, IGFBP2 and ANGPTL3 together with the standard cytokine cocktail of SCF, FL and TPO. The CD34+CD38-CD90+ phenotype can serve as a surrogate ex vivo surface marker for HSCs due to consistency with the in vivo CRU functional assay.
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