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Advancing Toward Reliable Blood Stem Cell Production for Regenerative Medicine

May 16, 2025
in Medicine
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Dr Anna Bigas lab, authors of the study
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In a groundbreaking study that could redefine the future of regenerative medicine and blood disorder treatments, researchers from the Josep Carreras Leukaemia Research Institute have identified a precise set of genes that can transform embryonic stem cells into fully functional hematopoietic stem and progenitor cells (HSPCs). This work, led by Dr. Anna Bigas and first-authored by Dr. Luis Galan Palma, represents a significant advance in the pursuit of producing blood-forming cells in the laboratory—an achievement long sought after in biomedical science for its potential to bypass donor shortages and revolutionize therapies for leukemia and other hematological diseases.

At the core of this research lies the elegant biology of stem cells, which possess the remarkable ability to differentiate into various specialized cell types, governed by tightly regulated genetic programs. The team’s challenge was to decode the complex genetic instructions that prompt a stem cell to commit specifically to a blood lineage. To tackle this, Dr. Bigas’ lab performed an unbiased, genome-wide screen in the murine model, systematically testing thousands of genes to identify those responsible for steering embryonic stem cells toward becoming hematopoietic progenitors. Their perseverance paid off when they uncovered a combination of seven critical genes that, when activated in a precise temporal manner, successfully reprogrammed mouse embryonic stem cells into HSPCs.

These newly induced HSPCs were not only phenotypically similar to natural blood stem cells but also demonstrated functional competence in vivo, as they engrafted in adult mice and regenerated a fully operational hematopoietic system. This system included the production of diverse blood cell lineages essential for immune defense, oxygen transport, and clotting. The functional validation of these lab-generated cells marks an essential milestone, proving that targeted gene activation can recapitulate the complexity of blood stem cell development, a feat that opens new therapeutic avenues.

Critically, the implications extend beyond mouse models. Dr. Bigas emphasizes the evolutionary conservation of these genes, noting their high sequence similarity across species, including humans. This conservation underpins the hypothesis that the mechanisms controlling stem cell fate and differentiation are fundamentally shared, suggesting that the mammalian blueprint revealed by this study could be applicable in human systems. Current efforts are underway to translate these findings to human embryonic stem cells, an essential step toward clinical application.

This breakthrough is part of a larger ERC synergy-funded initiative titled "Making Blood," which aspires to establish a cutting-edge platform capable of manufacturing human HSPCs on demand. Should this endeavor succeed, it could herald a new era in the treatment of blood-related disorders, where patients no longer require compatible donors for bone marrow transplantation—a procedure that often involves significant logistical and immunological challenges.

The research, recently published in the esteemed journal Blood, sheds light on the intricate gene regulatory networks that define hematopoietic fate decisions. By employing an unbiased genome-wide approach rather than relying on candidate gene trials, the team ensured a comprehensive and objective discovery process. Such thoroughness enhances the robustness of the findings and offers an expanded genetic toolkit for synthetic biology approaches aimed at blood regeneration.

Importantly, the study integrates developmental biology with translational medicine. Collaborations with experts in pediatric and developmental leukemia, Dr. Clara Bueno and Dr. Pablo Menéndez, have contextualized the importance of these genes in human disease, reinforcing the potential for targeted genetic manipulation to correct hematopoietic deficiencies or malignancies born from aberrant stem cell differentiation.

The potential of producing HSPCs ex vivo with precise genetic programming holds transformative promise for regenerative therapies, immune system reconstitution, and personalized medicine. It challenges current paradigms in transplantation biology, where matching donor and recipient immune profiles remains a critical barrier. By generating stem cells that can be tailored to individual patient needs, this technology could circumvent issues of compatibility and graft-versus-host disease.

The pathway forward, however, is complex. Translating murine genetic programs to human stem cells requires meticulous validation of gene function, timing, and expression levels, as minor deviations may result in incomplete or aberrant differentiation. Additionally, ensuring the safety and stability of genetically reprogrammed cells before clinical use is paramount, requiring comprehensive preclinical studies and regulatory scrutiny.

This work also highlights the synergistic power of interdisciplinary research centers such as the Josep Carreras Leukaemia Research Institute and the Hospital del Mar Research Institute, both recognized for excellence in biomedical science and translational research. Their combined expertise in hematology, oncology, stem cell biology, and clinical research facilitates rapid movement from bench to bedside, accelerating the development of novel therapies.

Funding from national and European scientific bodies, along with prestigious foundations, underscores the strategic importance placed on regenerative medicine for hematological disorders. Investment into projects like “Making Blood” reflects a broader commitment to harnessing the full potential of stem cells to address unmet clinical needs, including leukemia, anemia, and immunodeficiencies.

As research progresses, the scientific community remains vigilant but optimistic. Dr. Bigas’ group continues to unravel the complex genetic landscapes governing stem cell fate, poised to unlock further biological secrets and deliver therapeutic breakthroughs. Their work stands at the nexus of molecular biology, genetics, and clinical innovation, capturing imaginations and catalyzing hope among patients and researchers alike.

This landmark discovery revives the vision of producing a renewable source of healthy blood stem cells, potentially reshaping the management of hematological diseases. It paves the way for future innovations where laboratory-engineered cells could replace damaged or diseased marrow, offering cures where none existed before. The era of regenerative hematology may soon move from conceptual ambition to clinical reality.


Subject of Research: Cells

Article Title: An unbiased genomewide screen uncovers 7 genes that drive hematopoietic stem cell fate from mouse embryonic stem cells

News Publication Date: 10-Apr-2025

Web References:

  • Blood Journal Article
  • Josep Carreras Leukaemia Research Institute
  • Bigas Lab Stem Cells and Cancer Research

References:
Luis Galan Palma, Gayathri M Kartha, Maria Maqueda, Mercedes Barrero, Eric Canton, Arnau Iglesias, Jessica Gonzalez Miranda, Patricia Herrero Molinero, Raul Torres-Ruíz, Bernhard Payer, Clara Bueno, Pablo Menendez, Lluis Espinosa, Anna Bigas; An unbiased genomewide screen uncovers 7 genes that drive hematopoietic stem cell fate from mouse embryonic stem cells. Blood 2025; blood.2024027742. doi: 10.1182/blood.2024027742

Image Credits: Credit: Hospital del Mar Research Institute

Keywords: Stem cells, Blood cells, Bone marrow cells, Bone marrow

Tags: blood stem cell productionbreakthrough in blood disorder therapiesdonor shortages in blood therapiesembryonic stem cells differentiationgene identification in stem cell researchgenetic programs in stem cellshematopoietic stem and progenitor cellsleukemia treatment innovationsmurine model in biomedical studiesprecision medicine in hematologyregenerative medicine advancementsstem cell research and applications
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