The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue.
Hypoxic-ischemic injury is a prototype for insults characterized by extensive tissue loss. Seeding neural stem cells (NSCs) onto a polymer scaffold that was subsequently implanted into the infarction cavities of mouse brains injured by hypoxia-ischemia allowed us to observe the multiple reciprocal interactions that spontaneously ensue between NSCs and the extensively damaged brain: parenchymal loss was dramatically reduced, an intricate meshwork of many highly arborized neurites of both host- and donor-derived neurons emerged, and some anatomical connections appeared to be reconstituted. The NSC-scaffold complex altered the trajectory and complexity of host cortical neurites. Reciprocally, donor-derived neurons were seemingly capable of directed, target-appropriate neurite outgrowth (extending axons to the opposite hemisphere) without specific external instruction, induction, or genetic manipulation of host brain or donor cells. These "biobridges" appeared to unveil or augment a constitutive reparative response by facilitating a series of reciprocal interactions between NSC and host, including promoting neuronal differentiation, enhancing the elaboration of neural processes, fostering the re-formation of cortical tissue, and promoting connectivity. Inflammation and scarring were also reduced, facilitating reconstitution.
Park
Kook In
KI
Department of Pediatrics, Pharmacology, and Brain, Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea.
Teng
Yang D
YD
Snyder
Evan Y
EY
D000818:Animals; D001672:Biocompatible Materials; D001921:Brain / Q000473:pathology / Q000601:surgery; D002999:Clone Cells; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000601:surgery; D009416:Nerve Regeneration; D009434:Neural Pathways / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011100:Polyglycolic Acid; D019736:Prostheses and Implants; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000473:pathology*; D013784:Textiles
D001672:Biocompatible Materials; D011100:Polyglycolic Acid