Ischemic Cerebral Tissue and MCP-1 Enhance Rat Bone Marrow Stromal Cell Migration in Interface Culture

Exp Hematol. 2002 Jul;30(7):831-6. doi: 10.1016/s0301-472x(02)00829-9.

Abstract

Objective: Intravascular administration of bone marrow stromal cells (MSCs) restores function in animal models of neural injury and neurodegeneration. Adult MSCs administered intravenously to rat migrate and express neural phenotypes in ischemic brain. The aim of the present study was to investigate the mechanisms targeting MSC migration into the ischemic brain.

Methods: Monocyte chemoattractant protein-1 (MCP-1), a chemoattractant factor, was measured in rat ischemic brain at various time points after middle cerebral artery occlusion (MCAo) using a specific enzyme-linked immunosorbent assay system (ELISA). In addition, using a microchemotaxis chamber, we measured whether ischemic brain tissue extracts induce migration of MSCs and whether brain tissue extracts incubated with antibodies against MCP-1 reduce MSC migration.

Result: Our data indicate that ischemic brain MCP-1 levels significantly increase from 6 hours, peak at 48 hours after MCAo (p < 0.05), and thereafter gradually decrease. Brain tissue extract at 6 hours, 24 hours, and 48 hours after MCAo significantly increase MSC migration across the membrane of the microchemotaxis chamber compared to normal tissue (p < 0.05). However, when the ischemic brain tissue extracts are incubated with antibody against MCP-1, MSC migration is significantly reduced at 24 hours and 48 hours after MCAo compared to extracts without this antibody (p < 0.05).

Conclusion: Our data suggest that MCP-1 contributes to MSC migration into the ischemic brain tissue environment.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Transplantation*
  • Brain Chemistry
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Brain Ischemia / therapy
  • Cell Movement
  • Cells, Cultured / drug effects
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / antagonists & inhibitors
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / physiology*
  • Chemotaxis / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology*
  • Infarction, Middle Cerebral Artery / therapy
  • Models, Animal
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / physiology*
  • Rats
  • Receptors, CCR2
  • Receptors, Chemokine / drug effects
  • Recombinant Proteins / pharmacology
  • Stromal Cells / drug effects
  • Stromal Cells / transplantation*
  • Tissue Extracts / pharmacology

Substances

  • Antibodies, Monoclonal
  • Ccr2 protein, rat
  • Chemokine CCL2
  • Nerve Tissue Proteins
  • Receptors, CCR2
  • Receptors, Chemokine
  • Recombinant Proteins
  • Tissue Extracts