title: In vivo evaluation of a neural stem cell-seeded prosthesis.
abstract: Neural prosthetics capable of recording or stimulating neuronal activity may restore function for patients with motor and sensory deficits resulting from injury or degenerative disease. However, overcoming inconsistent recording quality and stability in chronic applications remains a significant challenge. A likely reason for this is the reactive tissue response to the devices following implantation into the brain, which is characterized by neuronal loss and glial encapsulation. We have developed a neural stem cell-seeded probe to facilitate integration of a synthetic prosthesis with the surrounding brain tissue. We fabricated parylene devices that include an open well seeded with neural stem cells encapsulated in an alginate hydrogel scaffold. Quantitative and qualitative data describing the distribution of neuronal, glial, and progenitor cells surrounding seeded and control devices are reported over four time points spanning 3 months. Neuronal loss and glial encapsulation associated with cell-seeded probes were mitigated during the initial week of implantation and exacerbated by 6 weeks post-insertion compared to control conditions. We hypothesize that graft cells secrete neuroprotective and neurotrophic factors that effect the desired healing response early in the study, with subsequent cell death and scaffold degradation accounting for a reversal of these results later. Applications of this biohybrid technology include future long-term neural recording and sensing studies.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Lurie Biomedical Engineering Building, 1101 Beal Ave., Ann Arbor, MI 48109-2099, USA. erinfred@umich.edu
authors.forename: E K
authors.initials: EK
authors.lastname: Purcell
authors.forename: J P
authors.initials: JP
authors.lastname: Seymour
authors.forename: S
authors.initials: S
authors.lastname: Yandamuri
authors.forename: D R
authors.initials: DR
authors.lastname: Kipke
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D002452:Cell Count; D016923:Cell Death; D002460:Cell Line; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011108:Polymers; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000295:instrumentation*; D013234:Stem Cells / Q000502:physiology*; D014992:Xylenes
chemical_list: D011108:Polymers; D014992:Xylenes; C011055:parylene