MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture.
Bone marrow stromal cells (MSCs) administered intravenously are effective in reducing neurological deficits after stroke in the rodent. These cells appear to selectively migrate and express neural phenotypes in ischemic brain. To elucidate the mechanisms targeting MSC migration into the ischemic brain, we measured, using a microchemotaxis chamber, the effect of select chemotactic factors and cytokines expressed in injured brain, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-8 (IL-8), on migration of human bone marrow stromal cells (hMSCs). In addition, we investigated whether tissue extracts prepared from rat ischemic brain at various times after middle cerebral artery occlusion (MCAo) induce migration of hMSCs. Our data indicate that MCP-1, MIP-1alpha and IL-8 enhance the migration of hMSCs. Ischemic brain tissue extracts at 24, 48 h and 1 week after ischemia significantly increase hMSC migration across the membrane compared to non-ischemic tissue (p<0.05). These data indicate that hMSCs are targeted by inflammatory chemotactic agents and cytokines and that ischemic brain attracts hMSCs.
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Lei
L
Wang
Yi
Y
Li
Xiaoguang
X
Chen
Jieli
J
Chen
Subhash C
SC
Gautam
Yongxian
Y
Xu
Michael
M
Chopp
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D018932:Chemokine CCL2 / Q000494:pharmacology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D019899:Paracrine Communication; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000166:cytology*
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins