Your browser doesn't support javascript.
loading
Integrin α4 Overexpression on Rat Mesenchymal Stem Cells Enhances Transmigration and Reduces Cerebral Embolism After Intracarotid Injection.
Cui, Li-Li; Nitzsche, Franziska; Pryazhnikov, Evgeny; Tibeykina, Marina; Tolppanen, Laura; Rytkönen, Jussi; Huhtala, Tuulia; Mu, Jing-Wei; Khiroug, Leonard; Boltze, Johannes; Jolkkonen, Jukka.
Afiliação
  • Cui LL; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Nitzsche F; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Pryazhnikov E; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Tibeykina M; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Tolppanen L; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Rytkönen J; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Huhtala T; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Mu JW; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Khiroug L; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Boltze J; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
  • Jolkkonen J; From the Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland (L.-l.C., J.-w.M., J.J.); Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany (F.N.); McGowan Institute for Regenerative Medicine, University of Pittsburgh
Stroke ; 48(10): 2895-2900, 2017 10.
Article em En | MEDLINE | ID: mdl-28916665
ABSTRACT
BACKGROUND AND

PURPOSE:

Very late antigen-4 (integrin α4ß1)/vascular cell adhesion molecule-1 mediates leukocyte trafficking and transendothelial migration after stroke. Mesenchymal stem cells (MSCs) typically express integrin ß1 but insufficient ITGA4 (integrin α4), which limits their homing after intravascular transplantation. We tested whether ITGA4 overexpression on MSCs increases cerebral homing after intracarotid transplantation and reduces MSC-borne cerebral embolism.

METHODS:

Rat MSCs were lentivirally transduced to overexpress ITGA4. In vitro transendothelial migration was assessed using a Boyden chamber assay. Male Wistar rats intracarotidly received 0.5×106 control or modified MSCs 24 hours after sham or stroke surgery. In vivo behavior of MSCs in the cerebral vasculature was observed by intravital microscopy and single-photon emission computed tomography for up to 72 hours.

RESULTS:

Transendothelial migration of ITGA4-overexpressing MSCs was increased in vitro. MSCs were passively entrapped in microvessels in vivo and occasionally formed large cell aggregates causing local blood flow interruptions. MSCs were rarely found in perivascular niches or parenchyma at 72 hours post-transplantation, but ITGA4 overexpression significantly decreased cell aggregation and ameliorated the evoked cerebral embolism in stroke rats.

CONCLUSIONS:

ITGA4 overexpression on MSCs enhances transendothelial migration in vitro, but not in vivo, although it improves safety after intracarotid transplantation into stroke rats.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Embolia Intracraniana / Integrina alfa4 / Transplante de Células-Tronco / Migração Transendotelial e Transepitelial / Células-Tronco Mesenquimais Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Embolia Intracraniana / Integrina alfa4 / Transplante de Células-Tronco / Migração Transendotelial e Transepitelial / Células-Tronco Mesenquimais Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article