title: Stem cell impregnated nanofiber stent sleeve for on-stent production and intravascular delivery of paracrine factors.
abstract: Stem cell therapies for atherosclerotic diseases are promising, but benefits remain modest with present cell delivery devices in part due to cell washout and immune attack. Many stem cell effects are believed mediated by paracrine factors (PFs) secreted by the stem cells which potentiate tissue repair via activation and enhancement of intrinsic host repair mechanisms We therefore sought to create an "intravascular paracrine factor factory" by harnessing stem cells on a stent using a nanofiber (NF) stent sleeve, and thus providing a sheltered milieu for cells to continuously produce PFs on-stent. The NF sleeve acts as a substrate on which stem cells grow, and as a semi-permeable barrier that protects cells from washout and host immune response while allowing free outward passage of PFs. NF stent sleeves were created by covering stents with electrospun poly-lactic-co-glycolic acid nanofibers and were then uniformly coated with mesenchymal stem cells (MSCs). NF sleeves blocked cell passage but did not hamper MSC attachment or proliferation, and did not alter MSC morphology or surface markers. NF sleeve MSCs continued to secrete PFs that were biologically active and successfully induced tubulogenesis in human endothelial cells. NF stent sleeves seeded with allogeneic MSCs implanted in pigs remained patent at 7 days without thrombotic occlusion or immune rejection. Our results demonstrate the feasibility of creating an intravascular PF factory using a stem cell impregnated NF stent sleeve, and pave the way for animal studies to assess the efficacy of local PF production to treat ischemic artery disease.
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: chwang7@jhmi.edu.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Johnston
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Gerstenblith
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Weiss
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Bogdan
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Asmi
authors.initials: A
authors.lastname: Panigrahi
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Leszczynska
authors.affiliation: Research and Exploratory Development Department, Johns Hopkins University Applied Physics Laboratory, Laurel, MD, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000792:Angiography; D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D002470:Cell Survival; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D016503:Drug Delivery Systems; D004867:Equipment Design; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D007511:Ischemia / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D057139:Nanofibers / Q000737:chemistry*; D010539:Permeability; D015607:Stents; D013552:Swine; D014184:Transplantation, Homologous
chemical_list: D020099:Coated Materials, Biocompatible
keywords: Coronary artery disease; Nanofiber; Paracrine factor; Peripheral artery disease; Stem cell