Interleukin-3 greatly expands non-adherent endothelial forming cells with pro-angiogenic properties
| Autor: | Denis Tvorogov, Stephen G. Worthley, Angel F. Lopez, Claudine S. Bonder, Lih Y. Tan, L. Frost, Lachlan M. Moldenhauer, Michaelia P. Cockshell, Katie Tooley, Kate A. Parham, Lisa M. Ebert |
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| Přispěvatelé: | Moldenhauer, Lachlan M., Cockshell, Michaelia P., Frost, Lachlan, Parham, Kate A., Tvorogov, Dennis, Tan, Lih Y., Ebert, Lisa M., Tooley, Katie, Worthley, Stephen, Lopez, Angel F., Bonder, Claudine S. |
| Rok vydání: | 2014 |
| Předmět: |
CD31
Male medicine.medical_treatment CD34 Cell Culture Techniques Cell- and Tissue-Based Therapy Myocardial Infarction Neovascularization Physiologic Biology Cell therapy Mice In vivo medicine Human Umbilical Vein Endothelial Cells Animals Humans Regeneration Progenitor cell lcsh:QH301-705.5 Cells Cultured Interleukin 3 Cell Proliferation Endothelial Progenitor Cells Medicine(all) Growth factor Myocardium Cell Biology General Medicine Cell biology Rats Endothelial stem cell lcsh:Biology (General) acute myocardial-infarction left-ventricular function progenitor cells cord blood regeneration enhancement vessel formation stromal cell topcare-ami stem-cells in-vivo Immunology Interleukin-3 Developmental Biology |
| Zdroj: | Stem Cell Research, Vol 14, Iss 3, Pp 380-395 (2015) |
| ISSN: | 1876-7753 |
| Popis: | Circulating endothelial progenitor cells (EPCs) provide revascularisation for cardiovascular disease and the expansion of these cells opens up the possibility of their use as a cell therapy. Herein we show that interleukin-3 (IL3) strongly expands a population of human non-adherent endothelial forming cells (EXnaEFCs) with low immunogenicity as well as pro-angiogenic capabilities in vivo, making their therapeutic utilisation a realistic option. Non-adherent CD133+ EFCs isolated from human umbilical cord blood and cultured under different conditions were maximally expanded by day 12 in the presence of IL3 at which time a 350-fold increase in cell number was obtained. Cell surface marker phenotyping confirmed expression of the hematopoietic progenitor cell markers CD133, CD117 and CD34, vascular cell markers VEGFR2 and CD31, dim expression of CD45 and absence of myeloid markers CD14 and CD11b. Functional experiments revealed that EXnaEFCs exhibited classical properties of endothelial cells (ECs), namely binding of Ulex europaeus lectin, up-take of acetylated-low density lipoprotein and contribution to EC tube formation in vitro. These EXnaEFCs demonstrated a pro-angiogenic phenotype within two independent in vivo rodent models. Firstly, a Matrigel plug assay showed increased vascularisation in mice. Secondly, a rat model of acute myocardial infarction demonstrated reduced heart damage as determined by lower levels of serum creatinine and a modest increase in heart functionality. Taken together, these studies show IL3 as a potent growth factor for human CD133+ cell expansion with clear pro-angiogenic properties (in vitro and in vivo) and thus may provide clinical utility for humans in the future. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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