Human mesenchymal stem cell grafts engineered to release adenosine reduce chronic seizures in a mouse model of CA3-selective epileptogenesis.
A novel generation of silk-based brain implants engineered to release adenosine was recently shown to provide robust seizure suppression in kindled rats. As a first step to develop stem cell-coated silk-based 3D-scaffolds for the therapeutic long-term delivery of adenosine we engineered human mesenchymal stem cells (hMSCs) to release adenosine. Here we demonstrate reduction of chronic seizures in a mouse model of CA3-selective epileptogenesis after infrahippocampal transplantation of adenosine-releasing hMSCs.
Li
Tianfu
T
Robert Stone Dow Neurobiology Laboratories, Legacy Research, 1225 NE 2nd Avenue, Portland, OR 97232, USA.
Ren
Gaoying
G
Kaplan
David L
DL
Boison
Detlev
D
D000241:Adenosine / Q000096:biosynthesis / Q000627:therapeutic use*; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000601:surgery; D006801:Humans; D007211:Indoles; D007608:Kainic Acid; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D023822:Tissue Engineering / Q000379:methods*; D014162:Transfection / Q000379:methods
D007211:Indoles; D035683:MicroRNAs; D049452:Green Fluorescent Proteins; C007293:DAPI; D000248:Adenosine Kinase; D000241:Adenosine; D007608:Kainic Acid