title: Mesenchymal stromal cell secretomes are modulated by suspension time, delivery vehicle, passage through catheter, and exposure to adjuvants.
abstract: Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections.
  
  
  
  MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed.
  
  
  
  Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed.
  
  
  
  Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration.
authors.affiliation: Stroke Program, McGovern Medical School at UTHealth, Houston, Texas, USA.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Parsha
authors.affiliation: Texas A&M, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Osman
authors.initials: O
authors.lastname: Mir
authors.affiliation: Stroke Program, McGovern Medical School at UTHealth, Houston, Texas, USA. Electronic address: nikunj.b.satani@uth.tmc.edu.
authors.forename: Nikunj
authors.initials: N
authors.lastname: Satani
authors.affiliation: Stroke Program, McGovern Medical School at UTHealth, Houston, Texas, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Interventional Neuroradiology/Endovascular Neurosurgery, Department of Neurology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Waldo
authors.initials: W
authors.lastname: Guerrero
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zhuyong
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Center for Clinical and Translational Sciences, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, McGovern Medical School at UTHealth, Houston, Texas, USA.
authors.forename: Peng R
authors.initials: PR
authors.lastname: Chen
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gee
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Division of Blood and Marrow Transplantation, Center for Cancer and Immunology Research, and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System and the George Washington University, Washington, DC, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.affiliation: Stroke Program, McGovern Medical School at UTHealth, Houston, Texas, USA.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Aronowski
authors.affiliation: Stroke Program, McGovern Medical School at UTHealth, Houston, Texas, USA.
authors.forename: Sean I
authors.initials: SI
authors.lastname: Savitz
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007472:Iohexol / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013535:Suspensions; D013997:Time Factors; D062666:Vascular Access Devices; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D013535:Suspensions; D042461:Vascular Endothelial Growth Factor A; D007472:Iohexol; D006493:Heparin
keywords: cytokines; delivery; mesenchymal stromal cell (MSC); secretome