Single-cell, high-throughput analysis of cell docking to vessel wall

Anna Andrzejewska, Adam Nowakowski, Tomasz Grygorowicz, Sylwia Dabrowska, Jarosław Orzel, Piotr Walczak, Barbara Lukomska, Miroslaw Janowski

Research output: Contribution to journalArticlepeer-review

Abstract

Therapeutic potential of mesenchymal stem cells (MSCs) has been reported consistently in animal models of stroke, with mechanism mainly through immunomodulation and paracrine activity. Intravenous injection has been a prevailing route for MSCs administration, but cell quantities needed when scaling-up from mouse to human are extremely high putting into question feasibility of that approach. Intra-arterial delivery directly routes the cells to the brain thus lowering the required dose. Cell engineering may additionally improve cell homing, further potentiating the value of intra-arterial route. Therefore, our goal was to create microfluidic platform for screening and fast selection of molecules that enhance the docking of stem cells to vessel wall. We hypothesized that our software will be capable of detecting distinct docking properties of naïve and ITGA4-engineered MSCs. Indeed, the cell flow tracker analysis revealed positive effect of cell engineering on docking frequency of MSCs (42% vs. 9%, engineered vs. control cells, p < 0.001). These observations were then confirmed in an animal model of focal brain injury where cell engineering resulted in improved homing to the brain. To conclude, we developed a platform to study the docking of cells to the vessel wall which is highly relevant for intraarterial cell targeting or studies on neuroinflammation.

Original languageEnglish (US)
Pages (from-to)2308-2320
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume39
Issue number11
DOIs
StatePublished - Nov 1 2019

Keywords

  • ITGA4
  • Mesenchymal stem cells
  • docking
  • mRNA
  • microfluidic assay
  • stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Single-cell, high-throughput analysis of cell docking to vessel wall'. Together they form a unique fingerprint.

Cite this