Melbourne researchers have achieved a groundbreaking milestone in developing blood stem cells that closely resemble those found in the human body. This discovery was published in Nature Biotechnology and marks a significant step forward in creating personalized treatments for children suffering from leukemia and bone marrow failure disorders.
Cell-based therapy, particularly stem cell therapy, offers new hope for patients with incurable diseases, where current treatments focus on symptom management rather than a cure. As a key component of regenerative medicine, it enhances the body’s repair mechanisms by stimulating or replenishing stem cells to restore tissue homeostasis and regeneration.
The research team has successfully overcome a long-standing obstacle in producing human blood stem cells in the lab. These lab-engineered cells can now create red cells, white blood cells, and platelets that are nearly identical to those found in the human embryo. This advancement holds the potential to revolutionize blood stem cells and bone marrow transplants.
The researchers stated that the ability to take any cell from a patient, reprogram it into a stem cell, and then transform these into specifically matched blood cells for transplantation will profoundly impact the lives of vulnerable patients. This innovative approach could provide life-saving solutions for children who previously had limited treatment options.
Before this breakthrough, the development of human blood stem cells capable of being transplanted into animal models of bone marrow failure had remained elusive. The team has now established a workflow that produces transplantable blood stem cells closely mirroring those in the human embryo. This achievement is particularly significant as these lab-grown cells can be generated at the scale and purity necessary for clinical applications.
The study involved injecting immune-deficient mice with lab-engineered human blood stem cells. The results demonstrated that these cells successfully developed into functional bone marrow, achieving levels comparable to those seen in umbilical cord blood cell transplants—a recognized standard of success in this field.
In addition, the research showed that these lab-grown stem cells could be frozen before being successfully transplanted into the mice. This preservation process mimics the methods used to store donor blood stem cells before transplantation into patients, further underscoring the clinical viability of this approach.
Ng et. al. emphasized the broader implications of these findings. Red blood cells are vital for oxygen transport, white blood cells serve as our immune defense, and platelets are essential for clotting to prevent bleeding. By perfecting stem cell methods that mimic the development of normal blood stem cells, personalized treatments for a range of blood diseases, including leukemias and bone marrow failure, can be developed.
The research team emphasized the potential of this research to address critical challenges in treating childhood blood disorders. Blood stem cell transplants are often crucial for life-saving treatments for these disorders. However, finding a perfectly matched donor is not always possible, leading to complications such as graft-versus-host disease. This occurs when the donor’s immune cells attack the recipient’s tissues, causing severe illness or even death. By developing patient-specific blood stem cells, these complications could be avoided, and the issue of donor shortages could be alleviated. Furthermore, this approach could work in conjunction with genome editing to correct the underlying genetic causes of blood diseases.
Leukemia treatment, despite advancements, has limitations that often necessitate stem cell transplantation (SCT) as a critical therapeutic option. Chemotherapy, the primary treatment, can lead to drug resistance and high relapse rates, especially in aggressive forms like acute myeloid leukemia (AML). Additionally, chemotherapy’s severe side effects, such as immune suppression and organ damage, reduce its long-term efficacy, particularly in advanced stages of the disease. Furthermore, different leukemia subtypes respond variably to standard treatments, making SCT necessary in many cases. SCT offers a chance to restore bone marrow function after chemotherapy or radiation damage, providing long-term curative potential through the regeneration of healthy blood cells. Allogeneic SCT, in particular, introduces the “graft-versus-leukemia” (GVL) effect, where donor immune cells attack remaining cancer cells, reducing relapse risk. As a personalized therapy, SCT also supports innovative treatments like gene therapy or CAR-T cell therapy, making it an essential approach when conventional leukemia treatments prove insufficient.
The current researchers stated that the next step in their research will be a Phase I clinical trial to test the safety of using these lab-grown blood cells in humans. This is expected to take place within the next five years. This groundbreaking research opens the door to a new era in personalized medicine, offering hope to countless children facing life-threatening blood disorders.
References
- Ng ES, Sarila G, Li JY, Edirisinghe HS, Saxena R, Sun S, et al. Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells. Nat Biotechnol. 2024 Sep 2;1–14.
- Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, et al. Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022 Aug 6;7:272.