The Regulation of Normal and Leukemic Hematopoietic Stem Cells by Niches

Abstract

The origin and propagation of normal and leukemic hematopoietic cells critically depend on their interplays with the hematopoietic microenvironment (or so-called niche), which represent important biological models for understanding organogenesis and tumorigenesis. Nevertheless, the anatomic and functional characterizations of the niche cells for normal hematopoietic stem cells (HSCs) have proved a formidable task. It is uncertain whether the combinational effects of a few sets of molecular niche elements, behind the longsought cellular architectures with preferred anatomic locations, actually meets the functional definition of HSC niche. Moreover, even much less is known about the niche components for numerous types of leukemiastem cells (LSCs) that originate via discrete cellular and molecular transforming mechanisms. However, one interesting scenario is emerging, i.e., the leukemia cells can positively remodel the hematopoietic microenvironment favorable for their competition over the normal hematopoiesis that co-exists within the same ecosystem. This property probably represents a previously unappreciated essential trait of a functional LSC. Obviously, the further exploration into how the hematopoietic microenvironment interplay with normal or malignant hematopoiesis will shed light onto the designing of novel types of niche-targeting therapies for leukemia.

The Interaction Between Niche and Hematopoietic Stem Cells

“…Schofield was the first to propose that HSCs was in association with other cells which determine their behavior [1][2][3][4]. Such a niche composed of specialized cells capable of supporting stem cells.…”

“…However, the osteoblastic niche theory was challenged by studies showing that osteoblasts depleted by biglycan (Bgn) deficiency or osteoblastic cells depleted by treatment with ganciclovir had no effect on HSCs frequency [11].…”

Novel Targeted Therapies for Eosinophil-Associated Diseases and Allergy

“…In the currently emerging scenario, LSC are thought to remodel the bone marrow niche to achieve a survival advantage over non-leukemic stem cells (76). One hypothesis is that hypoxic areas are enhanced in the leukemic bone marrow.…”

Characteristics of Bone Marrow Microenvironment in Multiple Myeloma Before and After Treatment

“…Проблема взаимоотношений «микроокружение -стволовая клетка» является одной из актуальнейших в современной биологии и медицине. Ключевыми структурами, определяющими развитие ГСК и их коммитированных в лимфоидном направлении потомков, являются нишеформирующие элементы стромального микроокружения костного мозга (КМ) [3,[10][11][12].…”

“…ГСК могут циркулировать в кровеносном русле и, находясь практически в любых тканях и органах, тем не менее функционируют в качестве стволовых клеток только при нахождении в определенном микроокружении (нише). Понимание гемопоэтической ниши значительно улучшилось за последние несколько лет, что, по крайней мере частично, связано с развитием новых методов клеточных исследований [3,5,6,[10][11][12].…”