Stem cell therapy for corals

Stem cell therapy for corals

Could medical approaches to stem cell therapy be a tool for coral resilience to heat stress? Benyamin Rosental, Senior Researcher, Assistant Professor at Ben-Gurion University of the Negev in Israel answers the compelling question here

Our lab at Ben-Gurion University of the Negev in Israel is interested in immunology and focuses on transplantation immunology, primarily at the level of immune cells. We focus on stem cell transplantation, especially hematopoietic stem cells, called “bone marrow transplantation”.

Coral Cellular Immunology Laboratory

The uniqueness of our laboratory at Ben-Gurion University of the Negev is that we use comparative/evolutionary approaches to understand basic conserved mechanisms in transplantation immunology. Our indisputable expertise in the field provides us with the tools to isolate stem cells and immune cells in organisms, which was not possible before. Through our collaborative work, we have implemented two important projects to help us understand cellular immunology and use stem cell therapies for corals. Our first project is to test the hypothesis that the immune system of corals is subjected to heat stress, which is part of the phenomenon of “coral bleaching”.

Our second project concerns the development of stem cell transplantation for corals as a potential cell therapy tool. This is comparable to bone marrow transplantation in humans, when we take healthy hematopoietic stem cells from a donor and transplant them into an individual with white blood cell immune deficiency so they can develop a healthy immune system. In corals, we would do that from an individual coral resistant to heat stress to a sensitive coral. In this portrait, we will explain how these two projects came about in an immunology laboratory in Israel, as well as the logic behind our research ideas.

Stem cell therapy
Pocillopora damicornis coral. By Mike Connelly.

Coral reefs under threat

Coral reefs are basic ecosystems, important for marine life as well as local human communities. Unfortunately, over the past few decades, coral reefs have been in steady decline due to human-associated stress, primarily heat stress conditions. Coral reefs are based on hard corals, which are colonial animals that create a calcium-based skeleton that is the foundation of coral reefs, physically and ecologically.

Some of these animal colonies live for tens or even hundreds of years and can reach diameters of several meters. A coral reef is built on many of these animals. Corals also contain symbiotic algae, which provide them with nutrients. Under severe and prolonged thermal stress, the symbiosis is broken and the algae leave the coral tissues, leading to coral bleaching and eventually coral death.

Optional tools for coral conservation

The scientific community and conservation groups are working hard to find solutions to the decline of coral reefs around the world. The basic tools for reducing stress on corals are reducing pollution, global warming and stress from fishing and physical disturbance. But these approaches are not enough, because due to global warming, even remote reefs are at risk and have suffered severe bleaching effects in recent years.

Interestingly, some individuals of the same species are more tolerant of death from heat stress. About 10% of corals survive under such conditions, which means they have resilience genes that make them more resistant to these stressors. Many ideas are based on using these individuals to renew coral reefs. The basis is to breed from these resilient corals, similar to plant breeding for agriculture.

Moreover, since corals are colonial animals, a fraction of the coral can also grow a new one. The main problem is the coral growth time depending on the species, but a few centimeters per year is the maximum. This means that renewing a reef will take several decades, but it is still only the beginning. And the big question that remains is how to help an existing coral that might be a hundred years old and the size of a small car withstand a future heat wave?

Stem cell therapy
Isolation and sorting of cell populations from the coral Pocillopora damicornis (Snyder et al., 2020).

Stem cell therapy

The approach of trying to transfer the characteristic of resilient individual corals is central to our research. This can go in two directions; we directly transfer stem cells with the resilience genotypes and their genes that allow resilience, as has been done in humans with a bone marrow transplant for more than 45 years now. The second direction concerns the understanding of the genes which allow the resilience of certain individuals, we believe that is the key.

Several laboratories are working to understand the genes that allow heat resistance. When this problem is solved, we will need a tool to transfer these genes to existing corals: this is called gene therapy and today it is carried out by isolating stem cells from an individual, by modifying the target genes and retransplanting them. Both of these directions are based on the ability to isolate and transplant stem cells from and to adult coral animals. These are certainly the tools that we develop in our laboratory.

Stem cells are self-renewing cells that live throughout the life of an organism and are capable of renewing tissues and different cells in the body. They will carry their original genes for life and create cells and tissues with the same characteristics, including, in this case, heat resistance.

How the project was born

During my postdoctoral research at Stanford University in the United States, I was stationed between the medical school and the Hopkins Marine Station and performed comparative transplantation immunology on the marine model organism. At that time, Dr. Traylor-Knowles was a postdoctoral researcher working on the genetic response of corals to heat stress and bleaching. She discovered that immune genes were up-regulated in response to heat stress. Dr. Traylor-Knowles and I then began working together on developing tools to isolate coral cells and characterize their immune system.

This research work continues in close collaboration, where we test the immune responses of corals to heat stress. This project is supported by the NSF-BSF Integrative and Organismal Systems (IOS) grant. Interestingly, during this research work, we isolated candidate coral stem cells, which intrigued the conservation organization Revive & Restore, which involved us in the Advanced Coral Toolkit program. Revive & Restore is the leading nonprofit conservation organization promoting the incorporation of biotechnologies into standard conservation practices and is based in Sausalito, California, USA https://reviverestore.org/corals.

The project that we started in 2021 in our laboratory was born from research ideas on cellular immune cells and stem cells in corals. In this research program, we are developing tools for the isolation, characterization and transplantation of coral stem cells. We are developing the tools for stem cell transplantation in models of anemones (species related to corals), and the next steps will concern different hard corals.

Isolation and transplantation of stem cells in Hexacorallia: towards cell therapy for corals. ERC-2020 Seed Grant, #948476 CoralStem.

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