Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats.
Transplantation of neural cells is a potential approach for stroke treatment, but disruption of tissue architecture may limit transplant efficacy. One strategy for enhancing the ability of transplants to restore brain structure and function is to administer cells together with biomaterial scaffolding. We electrocoagulated the distal middle cerebral artery in adult rats and, 3 weeks later, injected one of the following into the infarct cavity: artificial cerebrospinal fluid, Matrigel scaffolding, human embryonic stem cell-derived neuronal precursor cells, scaffolding plus cells, or cells cultured in and administered together with scaffolding. Five weeks after transplantation, the latter two groups showed approximately 50% and approximately 60% reductions, respectively, in infarct cavity volume. Rats given cells cultured in and administered together with scaffolding also showed (1) survival and neuronal differentiation of transplanted cells shown by immunostaining for neuronal marker proteins and cleaved caspase-3, and by patch-clamp recording, 8 weeks after transplantation and (2) improved outcome on tests of sensorimotor and cognitive functions, 4 to 9 weeks after transplantation. These results indicate that transplantation of human neural cells together with biomaterial scaffolding has the potential to improve the outcome from stroke, even when treatment is delayed for several weeks after the ischemic event.
Jin
Kunlin
K
Buck Institute for Age Research, Novato, California 94945, USA.
Mao
Xiaoou
X
Xie
Lin
L
Galvan
Veronica
V
Lai
Bin
B
Wang
Yaoming
Y
Gorostiza
Olivia
O
Wang
Xiaomei
X
Greenberg
David A
DA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D002448:Cell Adhesion; D003094:Collagen; D004338:Drug Combinations; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000628:therapy; D007797:Laminin; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000637:transplantation*; D018408:Patch-Clamp Techniques; D011509:Proteoglycans; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
D004338:Drug Combinations; D007797:Laminin; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen