Hematopoietic Stem Cells and Their Niche in Bone Marrow

Abstract

Extensive research has explored the functional correlation between stem cells and progenitor cells, particularly in blood. Hematopoietic stem cells (HSCs) can self-renew and regenerate tissues within the bone marrow, while stromal cells regulate tissue function. Recent studies have validated the role of mammalian stem cells within specific environments, providing initial empirical proof of this functional phenomenon. The interaction between bone and blood has always been vital to the function of the human body. It was initially proposed that during evolution, mammalian stem cells formed a complex relationship with the surrounding microenvironment, known as the niche. Researchers are currently debating the significance of molecular-level data to identify individual stromal cell types due to incomplete stromal cell mapping. Obtaining these data can help determine the specific activities of HSCs in bone marrow. This review summarizes key topics from previous studies on HSCs and their environment, discussing current and developing concepts related to HSCs and their niche in the bone marrow.

Keywords: bone marrow microenvironment; hematopoietic progenitor cells; hematopoietic stem cells; niche.

Figure 1

Hematopoietic stem cell (HSC) regulation in steady-state and hematological malignancies. This image shows the features of HSC regulation between normal conditions and hematological malignancy. In normal hematopoiesis, HSCs are activated in response to signals from the bone marrow microenvironment. Upon activation, HSCs undergo proliferation to increase their numbers and develop into multipotent progenitors (MPPs). MMPs can evolve into more committed lymphoid/myeloid progenitors and their respective sub-progenitors (e.g., GMP, MEP, etc.). These progenitor cells undergo further differentiation and maturation to give rise to the diverse range of blood cell types found in circulation. Each cell in the hematopoietic process can be distinguished by differentiation markers. This tightly regulated process of activation, proliferation, and differentiation ensures the continuous replenishment of blood cells to maintain homeostasis. When the HSCs and the progenitors within the developing HSCs become damaged, they can transform into leukemic stem cells (LSCs). LSCs possess self-renewal capabilities and aberrant differentiation, giving rise to leukemic blasts that result in leukemia. CLP: Common lymphoid progenitor. CMP: Common myeloid progenitor. GMP: Granulocyte–Macrophage progenitor. MEP: Megakaryocyte–erythrocyte progenitor. Pro-B: Progenitor cell-B. Pro-T: Progenitor cell-T. Pro-NK: Progenitor cell-NK. Pro-DC: Dendritic progenitor cell. MncP: Monocyte progenitor. GrP: Granulocytic progenitor. EryP: Erythrocytic progenitor. MkP: Megakaryocyte progenitor. NK cells: Natural killer cells.

Figure 2

An image showing bone marrow microenvironment with their components. It shows two BM niches, two bone marrow niches, and the endosteal and vascular niches. The endosteal niche and vascular niche are two crucial microenvironments within the BM. The endosteal niche, located near the bone surface, provides a specialized environment for hematopoietic stem cells (HSCs) to reside and self-renew. The osteoblast is considered the most important cell in the endosteal niche; hence, it is also referred to as the osteoblastic niche. In contrast, the vascular niche, adjacent to blood vessels, supports HSCs by supplying nutrients and signaling molecules necessary for their proliferation and differentiation. It is composed of endothelial cells lining the blood vessels, as well as pericytes and smooth muscle cells surrounding them. Together, these niches play integral roles in regulating the maintenance and function of HSCs in the bone marrow. CAR cell: CXCL12-abundant reticular cell. OPN: Osteopontin. ANG1: Angiopoietin-1, SCF: Stem cell factor.

Figure 3

Dynamics of immune reconstitution and associated risks in recipients’ bone marrow following hematopoietic stem cell transplantation. In the first few weeks after transplantation, innate immune cells recover swiftly. Common infections during this phase include bacterial and Candida infections due to the early deficiency in adaptive immune cells. Meanwhile, adaptive immune function, including T cells and B cells, exhibits prolonged deficiencies and gradually recovers, taking over 2 years to fully restore. Viral infections and those caused by non-Candidal molds become more common during this phase. Various clinical factors, including conditioning regimens, donor sources, and post-transplant events such as graft-versus-host disease (GVHD) and immunosuppression, exert influence over the immune reconstitution process, thereby modulating the associated infectious risks.