Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture.
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.


RESULTS
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).


CONCLUSIONS
Our data suggest that MCP-1 contributes to MSC migration into the ischemic brain tissue environment.
Department of Neurology, Division of Hematology and Medical Oncology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Lei
L
Wang
Yi
Y
Li
Jieli
J
Chen
Subhash C
SC
Gautam
Zhenggang
Z
Zhang
Mei
M
Lu
Michael
M
Chopp
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects; D016026:Bone Marrow Transplantation; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002465:Cell Movement; D002478:Cells, Cultured / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D051381:Rats; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000637:transplantation*; D014020:Tissue Extracts / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D009419:Nerve Tissue Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014020:Tissue Extracts