Clinical Significance of Hematopoietic Stem Cells

Corresponding Author:

Agnieszka J Turlo
Department of Clinical Microbiology, Edge Hill University, Ormskirk, Lancashire, UK
E-mail: AJturlo@liverpool.ac.uk

Received: 06-Nov-2023, Manuscript No. SRRM-23-122121; Editor assigned: 09-Nov-2023, Pre QC No. SRRM-23-122121 (PQ); Reviewed: 23-Nov-2023, QC No. SRRM-23-122121; Revised: 30-Nov-2023, Manuscript No. SRRM-23-122121 (R); Published: 07-Dec-2023, DOI: 10.37532/SRRM.2023.6(6).143-144

Introduction

The stem cells that give rise to different blood cells are called Hematopoietic Stem Cells (HSCs). We refer to this process as hemopoiesis. Through a process known as endothelial-to-hematopoietic transition, the earliest definitive HSCs in vertebrates develop from the ventral endothelial wall of the embryonic aorta within the (mid-gestational) aorta-gonad-mesonephros area. Red bone marrow, found in the centre of most bones, is where hemopoiesis takes place. The layer of the embryo known as the mesoderm is where the red bone marrow originates.

The process that produces all mature blood cells is called hematopoiesis. It must strike a balance between the massive production needs-an individual’s daily generation of over 500 billion blood cells-and the requirement to control the quantity of each blood cell type in circulation. The majority of hematopoiesis in vertebrates happens in the bone marrow and is produced by a few numbers of multipotent, extensively self-renewing hematopoietic stem cells.

Description

Hematopoietic stem cells can differentiate into myeloid and lymphoid blood cell lineages. Dendritic cell development involves both the myeloid and lymphoid lineages. Monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes, and platelets are examples of myeloid cells. T cells, B cells, natural killer cells, and innate lymphoid cells are examples of lymphoid cells.

Since hematopoietic stem cells were originally identified in 1961, the term has undergone development. Committed multipotent, oligopotent, and unipotent progenitors as well as cells with both short and long-term regeneration capacities are found in the hematopoietic tissue. In myeloid tissue, hematopoietic stem cells make up 1 in 10,000 of the cells.

Location: The region of the aorta, gonad and mesonephros, as well as the vitelline and umbilical arteries, contains the earliest hematopoietic stem cells during the development of embryos in both humans and mice. HSCs are also discovered in the placenta, yolk sac, embryonic head, and foetal liver a little later. Adults’ bone marrow contains hematopoietic stem cells, particularly in the sternum, femur, and pelvis. Peripheral blood and umbilical cord blood also contain minor amounts of these. Using a needle and syringe, stem and progenitor cells can be extracted from the pelvis at the iliac crest.

Functions

Haematopoiesis: The process, by which blood cells originate, known as hemopoiesis, depends on hematopoietic stem cells. Hematopoietic stem cells are multipotent, meaning they have the ability to self-renew and replenish all blood cell types. A very large number of daughter hematopoietic stem cells can be produced by the expansion of a very small number of parent stem cells. A tiny number of hematopoietic stem cells are employed in bone marrow transplantation to reconstruct the hematopoietic system, utilising this feature. This procedure suggests that two daughter hematopoietic stem cells must divide symmetrically after bone marrow transplantation.

Quiescence: Like all adult stem cells, hematopoietic stem cells mostly exist in a quiescent, or reversible, growth-arresting condition. Quiescent HSCs have a different metabolism that enables them to endure longer in the hypoxic bone marrow environment. Hematopoietic stem cells come out of quiescence to resume active cell division in response to injury or death. The pathways PI3K/AKT/mTOR and MEK/ERK control the change from dormancy to proliferation and reverse. Stem cell exhaustion, or the progressive depletion of viable hematopoietic stem cells in the bloodstream, can result from dysregulation of these transitions.

Mobility: Because they are more likely than other immature blood cells to cross the bone marrow barrier, hematopoietic stem cells may move via the blood from one bone’s marrow to another. They might mature into T cells if they become established in the thymus. In instances of extra-medullary haematopoiesis, such as foetuses. Additionally, hematopoietic stem cells may settle and proliferate in the spleen or liver.

Aging of hematopoietic stem cells

DNA damage: As we age, long-term hematopoietic stem cells accrue breaks in DNA strands. The extensive inhibition of DNA repair and response mechanisms that rely on HSC quiescence is linked to this accumulation. A mechanism called Non-Homologous End Joining (NHEJ) is responsible for fixing double-strand breaks in DNA.

In polymerase mutant mice, there is a 40% reduction in the amount of bone marrow cells, which includes many hematopoietic lineages, and hematopoietic cell development defects in several peripheral and bone marrow cell populations. Hematopoietic progenitor cells’ capacity to proliferate is similarly diminished. These traits are correlated with a decreased haematological tissue’s capacity to repair double-strand breaks.

Many lines of evidence, including the finding that long-term repopulation is flawed and gets worse over time, point to the premature ageing of hematopoietic stem cells in mice deficient in NHEJ factor 1. A human induced pluripotent stem cell model with a defect in NHEJ1 was used to demonstrate the critical function NHEJ1 plays in ensuring the survival of the first hematopoietic progenitors. The limited NHEJ1-mediated repair capacity in these NHEJ1 defective cells seems to be unable to handle DNA damage brought on by ionising radiation, physiological stress, and regular metabolism.

Loss of clonal diversity: According to a study, the clonal diversity of hematopoietic stem cells rapidly decreases at the age of 70, giving rise to a faster-growing subset. This finding supports a unique hypothesis of ageing that may facilitate healthy ageing. Remarkably, the Christa Muller-Sieburg team in San Diego, California, earlier reported in 2008 on the change in clonal diversity throughout ageing for the murine system.

Conclusion

With the therapeutic potential to treat a wide range of disorders, the field of hematopoietic stem cells remains at the forefront of regenerative medicine. There is currently research being done on the developmental origin, self-renewal, differentiation, molecular signature, and therapeutic potential of HSCs. The development of an ex vivo niche is the HSC field’s next frontier. The door would be opened for unrestricted genetic alteration of HSCs to help on-going efforts in gene therapy if the crucial support cells and the cytokines they released were identified.