Abstract

Production of sponge-derived bioactive compounds in vitro has been proposed as an alternative to wild harvest, aquaculture, and chemical synthesis to meet the demands of clinical drug development and manufacture. Until recently, this was not possible because there were no marine invertebrate cell lines. Recent breakthroughs in the development of sponge cell lines and rapid cell division in improved nutrient media now make this approach a viable option. We hypothesized that three-dimensional (3-D) cell cultures would better represent how sponges function in nature, including the production of bioactive compounds. We successfully cultured sponge cells in 3-D matrices using FibraCel® disks, thin hydrogel layers, and gel microdroplets (GMDs). For in vitro production of bioactive compounds, the use of GMDs is recommended. Nutrients and sponge products rapidly diffuse into and out of the 3-D matrix, the GMDs may be scaled up in spinner flasks, and cells and/or secreted products can be easily recovered. Research on scale-up and production is in progress in our laboratory.

Highlights

  • Sponges are one of the most prolific sources of marine natural products (MNPs) [1].many pharmaceutically relevant MNPs are found only in trace amounts within the source sponge [2,3], and it is neither economically nor ecologically feasible to harvest enough wild sponge biomass to supply the necessary quantities for clinical drug development and manufacture [3]

  • In vitro cultivation of sponge cells is another biological option for production of biomass or bioactive metabolites [5]

  • We have previously demonstrated that cells of the sponge Axinella corrugata could be immobilized on FibraCel® disks, and that the cultured cells continued to produce stevensine [11]

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Summary

Introduction

Sponges are one of the most prolific sources of marine natural products (MNPs) [1].many pharmaceutically relevant MNPs are found only in trace amounts within the source sponge [2,3], and it is neither economically nor ecologically feasible to harvest enough wild sponge biomass to supply the necessary quantities for clinical drug development and manufacture [3]. Sponges are one of the most prolific sources of marine natural products (MNPs) [1]. In vitro cultivation of sponge cells is another biological option for production of biomass or bioactive metabolites [5]. Due to their cellular organization, sponges can be dissociated into cells that will reaggregate and differentiate to form a functional sponge [6]. Cell culture allows for precise control of environmental variables and selection or optimization of conditions that favor increased production of biomass and/or bioactive metabolites

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