Crucial blood stem cell creation step uncovered by ISU researchers

NF-kB activation by Nod1 initiates hematopoietic stem cell specification.

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A microbial sensor, Nod1, fights infections and aids blood stem cell development, a breakthrough by an Iowa State University team led by Prof. Raquel Espin Palazon. This discovery, published in Nature Communications, suggests a potential method for creating patient-derived blood stem cells in labs, eliminating the need for bone marrow transplants. The study builds on Espin Palazon’s prior work, revealing the unique role of inflammatory signals in early embryo stages for vascular and blood formation.

Espin Palazon said, “This would eliminate the challenging task of finding compatible bone marrow transplant donors and the complications that occur after a transplant, improving the lives of many leukemia, lymphoma, and anemia patients.” 

Stem cells act as body factories, making and renewing cells. Pluripotent embryonic stem cells form any cell, while adult stem cells have specific roles. Blood stem cells, or hematopoietic stem cells, create all blood components. A lifetime supply is produced in embryos before birth. Espin Palazon’s team found an immune receptor activating in embryos, priming endothelial cells for stem cell transformation.

Espin Palazon said, “We know blood stem cells form from endothelial cells, but the factors that set up the cell to switch identity were enigmatic. We didn’t know that this receptor was needed or that it was needed this early, before blood stem cells even form.”

Discovering Nod1’s role in blood stem cell development is a breakthrough for scientists aiming to create stem cells from patients’ samples. This could revolutionize treating blood disorders without relying on bone marrow transplants. Self-derived stem cells may eliminate risks like graft-versus-host disease. Raquel Espin Palazon sees this as a significant advancement in regenerative medicine. The research team continues exploring the intricate process of blood stem cell formation, emphasizing the importance of understanding the timing for developing effective methods.

His collaboration with Children’s Hospital of Philadelphia supports ongoing research. Clyde Campbell, co-author, was trained by the hospital on protocols for induced pluripotent stem cells. Raquel Espin Palazon remains committed to advancing blood disorder therapies through her Iowa State University group. She envisions creating therapeutic-grade blood stem cells to cure patients. Other Iowa State co-authors and contributors from the University of Edinburgh and Children’s Hospital of Philadelphia played vital roles in the study.

The study reveals the vital role of Nod1 in blood stem cell development, offering potential alternatives to conventional treatments. Collaborations with the Children’s Hospital of Philadelphia enhance the research, emphasizing the goal of creating therapeutic-grade blood stem cells. The team envisions a future where patients can be treated with their self-derived stem cells, minimizing risks and transforming the landscape of regenerative medicine for blood disorders.

Journal reference:

  1. Cheng, X., Barakat, R., Pavani, G. et al. Nod1-dependent NF-kB activation initiates hematopoietic stem cell specification in response to small Rho GTPases. Nature Communications. DOI: 10.1038/s41467-023-43349-1.

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