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Osteoimmunology in Aging
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
Lia Ginaldi, Daniela Di Silvestre, Maria Maddalena Sirufo, Massimo De Martinis
Osteoclasts, derived from bone marrow precursors which give rise also to professional antigen presenting cells (APC) (dendritic cells and macrophages), are multinucleated myeloid cells, specialized to resorb bone by removing mineralized bone matrix through the production of lysosomal enzymes (tartrate-resistant acid phosphatase [TRAP] and catepsin k). Their differentiation from myeloid lineage precursors is driven by osteoblasts through the production of M-CSF, receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL), and other co-stimulatory factors [44]. Osteoclasts are not only bone resorbing cells, but also a source of cytokines that influence the activity of other cells. For example, they modulate the bone remodeling cycle by secreting clastokines that control osteoblast activity, and directly regulate the hematopoietic stem cell niche [45].
Breast Cancer Stem Cells and Their Niche: Lethal Seeds in Lethal Soil
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
Danuta Balicki, Brian Leyland-Jones, Max S. Wicha
In the case of hematopoietic stem cell niches, studies have focused on the endosteum, the inner surface of the bone that interfaces with the bone marrow. Regulation of hematopoietic stem cell function is governed by factors secreted by osteoblasts, osteoclasts, and stromal fibroblasts within the endosteum (8). Imaging data suggests that hematopoietic stem cells reside near the endosteum, and that this localization and maintenance is also usually adjacent to CXCL12-secreting reticular cells, irrespective of whether the hematopoietic stem cells are in vascular or endosteal locations (97,98). The stimulation via parathyroid hormone-related protein receptors (PPR) or an increase in number of osteoblastic cells in the periosteum with high levels of the Notch ligand Jagged1, enlarged the stem cell niche with a resultant increase in the number of hematopoietic stem cells with evidence of Notch1 activation in vivo (99). The activation of Notch1 has been shown to result in enhanced self-renewal of hematopoietic stem cells possibly by inducing self-renewal genes including Hesl (8). In addition, the bone morphogenetic protein signal has an essential role in inducing haematopoietic tissue during embryogenesis within the hematopoietic stem cell niche (100). Mesenchymal stem cells have been shown to improve engraftment of hematopoietic stem cells, and suppress graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. In addition, when tumor cells are injected into NOD/SCID mice in conjunction with mesenchymal stem cells, their growth is much faster as compared to the group receiving only tumor cells. To explain this observation, it was suggested that mesenchymal stem cells have the ability to form a cancer stem cell niche in which tumor cells can preserve their proliferative potential to sustain the malignant process (101).
Malignancy post-hematopoietic stem cell transplant in patients with primary immunodeficiency
Published in Expert Review of Clinical Immunology, 2020
The ability of certain antibodies to open up the hematopoietic stem cell niche is an exciting prospect which may allow conditioning in the future without the need for toxic chemotherapy. CD45 is selectively expressed on all leucocytes and hemopoietic progenitors but is absent on non-hemopoietic tissues. Straathoff and colleagues reported 16 patients with PID who were less than 1 year of age or had significant preexisting co-morbidities. The conditioning regimen comprised alemtuzumab 0 · 2 mg/kg daily for 3 days for unrelated donors, or 0 · 1 mg/kg daily for matched sibling donors on day – 8 to day – 6, clinical-grade rat anti-CD45 (YTH 24 · 5 and 54 · 12) 0 · 4 mg/kg on day – 5 to day – 2, fludarabine (30 mg/m2 daily for 5 days on day – 8 to day – 4) and cyclophosphamide (300 mg/m2 daily for 4 days on day – 7 to day – 4). Twelve patients were alive and well at the end of the study, one failed to engraft and was successfully re-transplanted and 3 died – none of conditioning toxicity. Donor chimerism was variable but high level and sufficient to cure disease in the survivors [69].