COGRAFTING WITH POLYMER-ENCAPSULATED HUMAN NERVE GROWTH FACTOR-SECRETING CELLS AND CHROMAFFIN CELL-SURVIVAL AND BEHAVIORAL RECOVERY IN HEMIPARKINSONIAN RATS

Encapsulated cell grafting is one approach for the delivery of neurotr ansmitters and/or neurotrophic factors to the brain. Baby hamster kidn ey (BHK) cells were genetically modified to secrete high levels of hum an nerve growth factor (hNGF). Following polymer encapsulation, these cells were implanted into the left lateral ventricle or the left stria tum 1.5 mm away from striatally cografted unencapsulated adrenal medul lary chromaffin cells in hemiparkinsonian rats. Although the animals r eceiving adrenal medulla alone or adrenal medulla with intraventricula r hNGF-secreting cell grafting did not show recovery of apomorphine-in duced rotational behavior, the animals receiving adrenal medulla with intrastriatal hNGF-secreting cell implants showed a significant recove ry of rotational behavior 2 and 4 weeks after transplantation. Histolo gical analysis revealed that in animals receiving adrenal medulla with intraventricular hNGF-secreting cell grafting, the number of tyrosine hydroxylase-immunoreactive (TH-IR) surviving chromaffin cells tended to be higher (approximately five to six times) than in animals receivi ng adrenal medulla alone; however, this increase did not reach statist ical significance. In contrast, in animals receiving adrenal medullary cells together with intrastriatal hNGF-secreting cells, the number of TH-IR surviving chromaffin cells was more than 20 times higher than t hat in animals receiving adrenal medullary cells alone. Analysis of re trieved capsules revealed that hNGF continued to be released by encaps ulated BHK-hNGF cells after 4 weeks in vivo. Moreover, histological an alysis confirmed the presence of numerous viable encapsulated BHK-hNGF cells. These results indicate the potential use of intrastriatal impl antation of encapsulated hNGF-secreting cells for augmenting the survi val of cografted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats. These data indicate that this appro ach may have potential application for treating Parkinson's disease.