# The Biology of Stem Cells in the Human Parasite Schistosoma Mansoni

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $478,102

## Abstract

Schistosomiasis ranks second (behind malaria) as the world’s most devastating parasitic disease.
Despite this, treatment relies on a single drug, Praziquantel (PZQ), that has marginal efficacy.
This disease is caused by Schistosoma flatworms (schistosomes) that live in the vasculature,
producing eggs that spur a variety of chronic pathologies that are exacerbated by the fact that
schistosomes can survive in the blood for decades. How these parasites thrive in this hostile
environment remains an open question. Our group discovered that adult schistosomes possess
a population of somatic stem cells, neoblasts, that are critical for tissue renewal. During our
studies of these cells we made a surprising discovery: mechanical injury induces a massive
increase in neoblast proliferation at the site of wounding. Because this mirrors what happens in
highly regenerative free-living planarian flatworms, we reasoned that schistosomes may possess
an uncharacterized regenerative capacity. Whole-body regeneration (i.e., regenerating
amputated heads) is not known to occur in schistosomes; yet, classic studies suggest that
treatment of adult worms with sub-lethal doses of PZQ results in extensive tissue damage that
the worms can repair. Likewise, we find that sublethal concentrations of PZQ induce neoblast
proliferation in adult parasites. Furthermore, rapidly growing juvenile schistosomes, which have a
massive number of neoblasts, are refractory to PZQ. Thus, PZQ sensitivity and neoblast number
are inversely correlated. Given these data, we hypothesize that neoblasts fuel regenerative
responses in the worm and we predict these regenerative responses are critical to the parasite’s
ability to respond to insults in vivo, including PZQ treatment. To test this hypothesis, we propose
two specific aims. In Specific Aim 1, we will use single cell RNA sequencing to describe the
cellular lineages that operate during parasite development and determine whether these linages
programs are “reactivated” in adult worms following injury. In Specific Aim 2, we will evaluate
how well schistosomes are able to restore form and function to their tissues following injury and
the extent to which tissue repair relies on neoblasts. We will additionally determine whether
neoblast-driven regenerative responses are essential for juvenile and adult parasite survival
following PZQ administration in vivo. Together, these studies will be the first to explore
schistosome regenerative responses on a molecular level. Because we predict that neoblasts
mediate tissue repair following PZQ-induced damage, these studies could also suggest that
targeting neoblasts may enhance the efficacy of PZQ, thereby transforming how we treat this
disease.

## Key facts

- **NIH application ID:** 10335945
- **Project number:** 5R01AI121037-07
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** James J Collins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $478,102
- **Award type:** 5
- **Project period:** 2016-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335945

## Citation

> US National Institutes of Health, RePORTER application 10335945, The Biology of Stem Cells in the Human Parasite Schistosoma Mansoni (5R01AI121037-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10335945. Licensed CC0.

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