scholarly journals Bone Marrow Adipocytes: The Enigmatic Components of the Hematopoietic Stem Cell Niche

2019 ◽  
Vol 8 (5) ◽  
pp. 707 ◽  
Author(s):  
Vincent Cuminetti ◽  
Lorena Arranz

Bone marrow adipocytes (BMA) exert pleiotropic roles beyond mere lipid storage and filling of bone marrow (BM) empty spaces, and we are only now beginning to understand their regulatory traits and versatility. BMA arise from the differentiation of BM mesenchymal stromal cells, but they seem to be a heterogeneous population with distinct metabolisms, lipid compositions, secretory properties and functional responses, depending on their location in the BM. BMA also show remarkable differences among species and between genders, they progressively replace the hematopoietic BM throughout aging, and play roles in a range of pathological conditions such as obesity, diabetes and anorexia. They are a crucial component of the BM microenvironment that regulates hematopoiesis, through mechanisms largely unknown. Previously considered as negative regulators of hematopoietic stem cell function, recent data demonstrate their positive support for hematopoietic stem cells depending on the experimental approach. Here, we further discuss current knowledge on the role of BMA in hematological malignancies. Early hints suggest that BMA may provide a suitable metabolic niche for the malignant growth of leukemic stem cells, and protect them from chemotherapy. Future in vivo functional work and improved isolation methods will enable determining the true essence of this elusive BM hematopoietic stem cell niche component, and confirm their roles in a range of diseases. This promising field may open new pathways for efficient therapeutic strategies to restore hematopoiesis, targeting BMA.

2021 ◽  
Author(s):  
Inci Cevher Zeytin ◽  
Berna Alkan ◽  
Cansu Ozdemir ◽  
Duygu Cetinkaya ◽  
FATMA VISAL OKUR

Abstract Background Patients with osteopetrosis present with defective bone resorption caused by the lack of osteoclast activity and hematopoietic alterations, but their bone marrow hematopoietic stem/progenitor cell and osteoclast contents might be different. Osteoclasts recently have been described as the main regulators of HSCs niche, however, their exact role remains controversial due to the use of different models and conditions. Investigation of their role in hematopoietic stem cell niche formation and maintenance in osteopetrosis patients would provide critical information about the mechanisms of altered hematopoiesis. We used patient-derived induced pluripotent stem cells (iPSCs) to model osteoclast defect and hematopoietic niche compartments in vitro. Methods iPSCs were generated from peripheral blood mononuclear cells of patients carrying TCIRG1 mutation. iPSC lines were differentiated first into hematopoietic stem cells-(HSCs), and then into myeloid progenitors and osteoclasts using a step-wise protocol. Then, we established different co-culture conditions with bone marrow-derived hMSCs and iHSCs of osteopetrosis patients as an in vitro hematopoietic niche model to evaluate the interactions between osteopetrotic-HSCs and bone marrow-derived MSCs as osteogenic progenitor cells. Results We first demonstrated myeloid-skewed hematopoietic differentiation potential of osteopetrotic iPSC-derived hematopoietic progenitors and phenotypically normal and functionally defective osteoclast formation. Upon co-culture with healthy iHSCs, the expression of the genes involved in HSC homing and maintenance (Ang-1, Sdf-1, Jagged-1, N-Cadherine, Kit-L, Opn) in osteopetrotic MSCs which revealed impaired osteogeneic differentiation, as well as their attraction ability over HSCs recovered significantly. Similar change in the phenotype of osteopetrotic iHSCs occured when they interacted with healthy MSCs. Conclusion Our results establish significant alterations in both MSC and HSC compartments of the hematopoietic niche in osteopetrosis patients, which are restored with normal MSC activity supporting the role of defective osteoclasts in all these processes.


2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii289-iii289
Author(s):  
V V V Hira ◽  
J R Wormer ◽  
H Kakar ◽  
B Breznik ◽  
B van der Swaan ◽  
...  

2019 ◽  
Vol 25 (4) ◽  
pp. 701-701 ◽  
Author(s):  
Maria Maryanovich ◽  
Ali H. Zahalka ◽  
Halley Pierce ◽  
Sandra Pinho ◽  
Fumio Nakahara ◽  
...  

2019 ◽  
Vol 76 ◽  
pp. S45
Author(s):  
Fumio Nakahara ◽  
Daniel Borger ◽  
Qiaozhi Wei ◽  
Sandra Pinho ◽  
Maria Maryanovich ◽  
...  

2013 ◽  
Vol 22 (23) ◽  
pp. 3052-3061 ◽  
Author(s):  
Naser Ahmadbeigi ◽  
Masoud Soleimani ◽  
Mohammad Vasei ◽  
Yousof Gheisari ◽  
Yousef Mortazavi ◽  
...  

2017 ◽  
Vol 106 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Noboru Asada ◽  
Shoichiro Takeishi ◽  
Paul S. Frenette

Sign in / Sign up

Export Citation Format

Share Document