Brush Up: Hematopoietic Stem Cells and Their Role in Development and Disease Therapy

What Are Hematopoietic Stem Cells and Why Are They Important? Hematopietic stem cells (HSCs) are multipotent cells found in the blood and bone marrow with the ability to self-renew and differentiate into multiple cell types during bone marrow hematopoiesis. Clinicians use HSCs to replace or repopulate a patient’s blood as a form of regenerative medicine. Research into HSC development and aging facilitates better in vitro HSC expansion and broadens their potential for disease treatment, enhancing their clinical therapeutic effects.

How Hematopoietic Stem Cells Develop
HSCs begin their development during embryogenesis in the dorsal aortic tissue and are additionally found in the placenta, yolk sac, and fetal liver. This fetal hematopoiesis process is necessary to produce the blood cells required for tissue development while generating a pool of undifferentiated HSCs. At birth, these HSCs migrate into and populate the newly-formed bone marrow and maintain a steady state of self-renewal and differentiation.1 HSCs function by producing red blood cells, platelets, and white blood cells throughout life, maintaining their levels following bleeding and infection. HSCs generally give rise to partly differentiated but proliferative progenitors, which differentiate into mature cells. Because of this process, true HSCs are relatively rare in the human body.2

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 Using Hematopoietic Stem Cells for Research and Treatment 
Hematopoietic stem cell transplants
For more than 60 years, hematopoietic stem cell transplants (HSCTs) have been the most common form of HSC therapy, and are a standard option for treating hematologic malignancies, immunodeficiency, and defective hematopoiesis disorders. HSCs are now derived from multiple sources, such as peripheral and cord blood and bone marrow. Before transplantation, the receiving patient must undergo severe immunosuppressive procedures to prevent rejection of the new stem cells.3

Hematopoietic stem cell isolation
The most common HSC isolation method involves removing blood cells from plasma using density gradient centrifugation followed by magnetic bead isolation using the CD34+ surface marker, a general marker for all hematopoietic progenitors. Using flow cytometry, scientists sort specific HSC cell types based on common cell surface markers.4  Clinicians then intravenously infuse these cells into the receiver patient’s marrow where they engraft and repopulate the blood and immune system. In blood cancers such as leukemias and lymphomas, restoration of the blood system by HSCT allows patients to receive high-dose chemotherapy treatments, ridding them of malignant cells. In patients with red blood cell conditions where continuous blood transfusions are not an option, such as thalassemia major, HSCT results in 80 percent disease-free survival.5

Hematopoietic stem cells in gene and tissue regeneration therapy
Bone marrow hematopoietic stem cells also differentiate into cells of other lineages, such as endothelial cells, cardiomyocytes, neural cells, and hepatocytes, in a process called transdifferentiation. Because adult stem cells are rare, understanding the mechanisms behind HSC transdifferentiation could provide an additional source of tissue-specific multipotent cells and influence future clinical methods for tissue regeneration. HSCs can also help repair injured organs by releasing regenerative cytokines and recruiting cells to the damage site.5 Some of the latest advances in HSC therapeutic research involve using methods such as CRISPR for correcting genetically-defective HSCs. These methods will allow a patient to receive their own genetically-compatible (syngeneic) HSCs. These are called allogeneic transplants and are more effective at avoiding graft-versus-host disease, a condition where transplants from a donor are rejected by the recipient’s body, leading to an immune response against other tissues and organs. Creating genetically-corrected induced pluripotent stem cells (iPSCs) from patient skin tissues and differentiating them into HSCs has also been an active area of research, although current methods remain costly and time-consuming.6  Further research is necessary to take advantage of these remarkable multipotent cells in disease therapies.

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References

1. H.K. Mikkola, S.H. Orkin, “The journey of developing hematopoietic stem cells,” Development, 133(19):3733-44, 2006.

2. G.M. Crane et al., “Adult haematopoietic stem cell niches,” Nat Rev Immunol, 17(9):573-90, 2017.

3. S. Giralt, M.R. Bishop, “Principles and overview of allogeneic hematopoietic stem cell transplantation,” Cancer Treat Res, 144:1-21, 2009.

4. B. Kumar, S.S. Madabushi, “Identification and isolation of mice and human hematopoietic stem cells,” Methods Mol Biol, 1842:55-68, 2018.

5. J.Y. Lee, S.H. Hong, “Hematopoietic stem cells and their roles in tissue regeneration,” Int J Stem Cells, 13(1):1-12, 2020.

6. S. Demirci et al., “Hematopoietic stem cells from pluripotent stem cells: Clinical potential, challenges, and future perspectives,” Stem Cells Transl Med, 9(12):1549-57, 2020.

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Source: the-scientist.com

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