Busch, Caroline and Nyamondo, Kudzai and Wheadon, Helen (2024) Complexities of modelling the bone marrow microenvironment to facilitate haematopoietic research. Experimental Hematology, 135: 104233. ISSN 0301-472X

Abstract

Haematopoiesis occurs in the bone marrow (BM), within a specialised microenvironment referred to as the stem cell niche, where the haematopoietic stem cells (HSCs) reside and are regulated for quiescence, self-renewal and differentiation through intrinsic and extrinsic mechanisms. The BM contains at least two distinctive HSC supportive niches: an endosteal osteoblastic niche, which supports quiescence and self-renewal and a more vascular/peri-sinusoidal niche that promotes proliferation and differentiation. Both associate with supporting mesenchymal stromal cells (MSCs). Within the more hypoxic osteoblastic niche, HSCs specifically interact with the osteoblasts that line the endosteal surface, which secrete several important HSC quiescence and maintenance regulatory factors. In vivo imaging indicates that the HSCs and progenitors located further away, in the vicinity of sinusoidal endothelial cells, are more proliferative. Here HSCs interact with endothelial cells via specific cell adhesion molecules. Endothelial cells also secrete several factors important for HSC homeostasis and proliferation. In addition, HSCs and MSCs are embedded within the extracellular matrix (ECM), an important network of proteins such as collagen, elastin, laminin, proteoglycans, vitronectin and fibronectin. The ECM provides mechanical characteristics such as stiffness and elasticity important for cell behaviour regulation. ECM proteins are also able to bind, sequester, display and distribute growth factors across the BM, thus directly affecting stem cell fate and regulation of haematopoiesis. These important physical and chemical features of the BM require careful consideration when creating three dimensional models of the BM.

People
Busch, Caroline
Author

Busch, Caroline and Nyamondo, Kudzai and Wheadon, Helen (2024) Complexities of modelling the bone marrow microenvironment to facilitate haematopoietic research. Experimental Hematology, 135: 104233. ISSN 0301-472X

Busch, Caroline and Mulholland, Theresa and Zagnoni, Michele and Dalby, Matthew and Berry, Catherine and Wheadon, Helen (2023) Overcoming BCR::ABL1 dependent and independent survival mechanisms in chronic myeloid leukaemia using a multi-kinase targeting approach. Cell Communication and Signaling, 21: 342. ISSN 1478-811X

See full publications list
Nyamondo, Kudzai
Author

Busch, Caroline and Nyamondo, Kudzai and Wheadon, Helen (2024) Complexities of modelling the bone marrow microenvironment to facilitate haematopoietic research. Experimental Hematology, 135: 104233. ISSN 0301-472X

Nyamondo, Kudzai and Wheadon, Helen (2024) Microenvironment alterations through time leading to myeloid malignancies. British Journal of Pharmacology, 181 (2). pp. 283-294. ISSN 0007-1188

See full publications list
Wheadon, Helen
Author

Donnelly, Hannah and Ross, Ewan and Xiao, Yinbo and Hermantara, Rio and Taqi, Aqeel and Doherty-Boyd, W. Sebastian and Cassels, Jennifer and Tsimbouri, Penelope M. and Dunne, Karen M. and Hay, Jodie and Cheng, Annie and Meek, R.M. Dominic and Jain, Nikhil and West, Christopher and Wheadon, Helen and Michie, Alison M. and Peault, Bruno and West, Adam G. and Salmeron-Sanchez, Manuel and Dalby, Matthew J. (2024) Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells. Nature Communications, 15: 5791. ISSN 2041-1723

Busch, Caroline and Nyamondo, Kudzai and Wheadon, Helen (2024) Complexities of modelling the bone marrow microenvironment to facilitate haematopoietic research. Experimental Hematology, 135: 104233. ISSN 0301-472X

Dawson, Amy and Zarou, Martha M. and Prasad, Bodhayan and Bittencourt-Silvestre, Joana and Zerbst, Désirée and Himonas, Ekaterini and Hsieh, Ya-Ching and van Loon, Isabel and Rodriguez Blanco, Giovanny and Ianniciello, Angela and Kerekes, Zsombor and Krishnan, Vaidehi and Agarwal, Puneet and Almasoudi, Hassan and McCluskey, Laura and Hopcroft, Lisa E.M. and Scott, Mary T. and Baquero, Pablo and Dunn, Karen and Vetrie, David and Copland, Mhairi and Bhatia, Ravi and Coffelt, Seth B. and Tiong, Ong Sin and Wheadon, Helen and Zanivan, Sara and Kirschner, Kristina and Helgason, G. Vignir (2024) Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nature Communications, 15: 1090. ISSN 2041-1723

See full publications list
Texts
209:217
lightbox image
326022.pdf - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
Information
Library

View Item