Cells encapsulated in alginate: A potential system for delivery of recombinant proteins to malignant brain tumours

Growth and progression of malignant brain tumours occurs in a micromilieu c onsisting of both tumour and normal cells. Several proteins have been ident ified with the potential of interfering directly with tumour cells or with the neovascularisation process, thereby inhibiting tumour growth. A continu ous delivery of such inhibitory proteins to the tumour microenvironment by genetically engineered cells could theoretically be of considerable therape utic importance. In this study we have investigated the growth characterist ics of cells encapsulated in alginate, which represents a potential deliver y system for recombinant proteins that may have antitumour effects. Three d ifferent cell lines, NHI 3T3, 293 and BT4C were encapsulated in alginate, w hich is an immune-isolating substance extracted from brown seaweed. The enc apsulated cells were observed at specific intervals during a 4-month period after in vitro propagation and as transplants into the cortex of BD-IX rat s. Morphological studies showed that encapsulated cells proliferated and fo rmed spheroids within the alginate in the in vitro cultures and after impla ntation into the brain. Even after 4 months in vivo a substantial amount of living cells were observed within the alginate beads. A vigorous infiltrat ion of mononuclear cells was observed in the brain bordering the alginate b eads, one week after implantation. However, there was a gradual decrease of mononuclear cells at the border zone beyond the first week of implantation . The majority of inflammatory cells were reactive microglia and invading m onocytes, as verified by immunohistochemistry. The data further shows that alginate encapsulated cells can be frozen in liquid N-2 and will retain the ir viability and proliferative capacity. (C) 1999 Published by Elsevier Sci ence Ltd on behalf of ISDN. All rights reserved.