REVIEW Cell Cultures from Marine Invertebrates: New Insights for Capturing Endless Stemness Baruch Rinkevich Received: 14 November 2010 / Accepted: 13 December 2010 / Published online: 7 January 2011 # Springer Science+Business Media, LLC 2011 Abstract Despite several decades of extensive research efforts, there is yet no single permanent cell line available from marine invertebrates as these cells stop dividing in vitro within 24–72 h after their isolation, starting cellular quiescence. This ubiquitous quiescent state should be modified in a way that at least some of the quiescent cells will become pluripotent, so they will have the ability to divide and become immortal. Following the above need, this essay introduces the rationale that the discipline of marine invertebrates’ cell culture should gain from applying of two research routes, relevant to mammalian systems but less explored in the marine arena. The first is the use of adult stem cells (ASC) from marine organisms. Many marine invertebrate taxa maintain large pools of ASC in adulthood. Ample evidence attests that these cells from sponges, cnidarians, flatworms, crustaceans, mollusks, echinoderms, and ascidians play important roles in mainte- nance, regeneration, and asexual cloning, actively prolifer- ating in vivo, resembling the vertebrates’ cancer stem cells features. The second route is to target resting somatic cell constituents, manipulating them in the same way as has recently been performed on mammalian induced pluripotent stem (iPS) cells. While “iPS cells” are the outcome of an experimental manipulation, ASC are natural and rather frequent in a number of marine invertebrates. Above two cell categories reveal that there are more than a few types of seeds (cells) waiting to be sowed in the right soil (in vitro environmental conditions) for acquiring stemness and immortality. This rationale carries the potential to revolu- tionize the discipline of marine invertebrate cell cultures. When cultured “correctly,” ASC and “iPS cells” from marine invertebrates may stay in their primitive stage and proliferate without differentiating into cells lineages, har- nessing the stem cell’ s inherent abilities of self-replication versus differentiated progenies, toward the development of immortal cell lines. Keywords Cell cultures . Dedifferentiation . iPS cells . Marine invertebrates . Stem cells Prospectus The primary vision for the research on invertebrate cell culture methodologies has been the development of immortal cell lines, amenable to a wide range of applica- tions and needs (Mothersill and Austin 2000; Smagghe et al. 2009). It also applies to the sector of cell cultures from terrestrial invertebrates that have witnessed dramatic devel- opment. Whereas during the middle 1970s, about 70 cell lines from different species of insects and ticks were available (Hink 1979), three decades later, there is an impressive and diverse list of over 500 cell lines from insects alone, representing numerous insect orders and various tissue sources (reviewed in Smagghe et al. 2009). This rapid growth in the number of cell lines from terrestrial invertebrates does not reflect the status of the marine invertebrates sector. Although limited success has been achieved, following several decades of extensive research efforts on marine invertebrate cell cultures and despite the substantial demand of these cell cultures for numerous applications, there is yet no single permanent proliferating cell line available from any marine inverte- brate (Rinkevich et al. 1994; Bayne 1998; Rinkevich 1999, B. Rinkevich (*) Israel Oceanographic and Limnological Research, National Institute of Oceanography, Tel-Shikmona, P.O. Box 8030, Haifa 31080, Israel e-mail: buki@ocean.org.il Mar Biotechnol (2011) 13:345–354 DOI 10.1007/s10126-010-9354-3