Innovations and Advances in Schistosome Stem Cell Research

Abstract

Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these diverse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development; these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel individual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.

Schistosoma mansoni Fibroblast Growth Factor Receptor A Orchestrates Multiple Functions in Schistosome Biology and in the Host-Parasite Interplay

“…Currently no human vaccines are available and, as clinical treatment relies entirely on the single drug praziquantel, the potential emergence of drug resistance is an ever-present concern (1). Recent studies have demonstrated that stem cells play vital roles in driving and maintaining the complex schistosome life cycle (4)(5)(6)(7)(8). Adult schistosomes parasitize mammals and lay eggs many of which eventually escape these definitive hosts in feces or urine.…”

“…The fibroblast growth factor (FGF) signaling pathway in mammals is critically involved in a variety of processes during embryonic development and adult homeostasis through promoting cell proliferation, cell differentiation, cell survival, tissue repair/regeneration, drug resistance, and apoptosis (7,(11)(12)(13)(14)(15). Significantly, FGF signaling is crucial in stem cell control in various model systems including both vertebrates (5,(16)(17)(18) and invertebrates (14,(19)(20)(21)(22). The mammalian FGF pathway is activated by binding FGF ligands to FGFRs, thereby phosphorylating mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B, also called PKB), phospholipase C gamma (PLCg), and signal transducers and activators of transcription (STAT) (23)(24)(25).…”

Comparative transcriptome profiles of Schistosoma japonicum larval stages: Implications for parasite biology and host invasion

“…In recent years, it was shown that schistosomes, like the planarians, also contain stem cells. There are two major stem cells that play in the different life stages during intramolluscan and intramammalian development, including the germinal cells of sporocysts involved in asexual reproduction and the neoblast of adult worms involved in sexual reproduction [ 72 ]. Germinal cells have similar morphology with the neoblasts of planarians, they have a high nuclear to cytoplasmic ratio, an open chromatin structure and a large nucleolus [ 73 ].…”

The Search for a Schistosomiasis Vaccine: Australia’s Contribution

“…Another fledgling area where Australian vaccinologists can make a mark is the establishment of schistosome stem cell lines to advance schistosomiasis vaccine research [ 124 ]. The availability of such self-renewable resources can provide a new platform to study stem cell behavior and regulation, and to undertake studies on important areas of schistosome biology, reproductive development and survival.…”

“…Another fledgling area where Australian vaccinologists can make a mark is the establishment of schistosome stem cell lines to advance schistosomiasis vaccine research [124].…”