title: Retention of stemness and vasculogenic potential of human umbilical cord blood stem cells after repeated expansions on PES-nanofiber matrices.
abstract: Despite recent advances in cardiovascular medicine, ischemic diseases remain a major cause of morbidity and mortality. Although stem cell-based therapies for the treatment of ischemic diseases show great promise, limited availability of biologically functional stem cells mired the application of stem cell-based therapies. Previously, we reported a PES-nanofiber based ex vivo stem cell expansion technology, which supports expansion of human umbilical cord blood (UCB)-derived CD133(+)/CD34(+) progenitor cells ∼225 fold. Herein, we show that using similar technology and subsequent re-expansion methods, we can achieve ∼5 million-fold yields within 24 days of the initial seeding. Interestingly, stem cell phenotype was preserved during the course of the multiple expansions. The high level of the stem cell homing receptor, CXCR4 was expressed in the primary expansion cells, and was maintained throughout the course of re-expansions. In addition, re-expanded cells preserved their multi-potential differential capabilities in vitro, such as, endothelial and smooth muscle lineages. Moreover, biological functionality of the re-expanded cells was preserved and was confirmed by a murine hind limb ischemia model for revascularization. These cells could also be genetically modified for enhanced vasculogenesis. Immunohistochemical evidences support enhanced expression of angiogenic factors responsible for this enhanced neovascularization. These data further confirms that nanofiber-based ex-vivo expansion technology can generate sufficient numbers of biologically functional stem cells for potential clinical applications.
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Joseph
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Manjusri
authors.initials: M
authors.lastname: Das
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Kanji
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Lu
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Reeva
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Department of Pathology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Chakroborty
authors.affiliation: Department of Pathology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Chandrani
authors.initials: C
authors.lastname: Sarkar
authors.affiliation: Department of Pathology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Materials Science and Engineering & Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Mao
authors.affiliation: Department of Pathology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Sujit
authors.initials: S
authors.lastname: Basu
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Pompili
authors.affiliation: Stem Cell Research Laboratory, Davis Heart and Lung Research Institute, Wexner Medical Center at The Ohio State University, Columbus, OH, USA. Electronic address: hiranmoy.das@osumc.edu.
authors.forename: Hiranmoy
authors.initials: H
authors.lastname: Das
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D016513:Mice, SCID; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010641:Phenotype; D011108:Polymers / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D011108:Polymers; D013450:Sulfones; C022840:polyether sulfone
keywords: CD34(+) stem cells; Limb ischemia; NOD/SCID mice; PES-nanofiber; Proangiogenic growth factors; Re-expansion