Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

Abstract

The adult bone marrow (BM) niche is a complex entity where a homeostatic hematopoietic system is maintained through a dynamic crosstalk between different cellular and non-cellular players. Signaling mechanisms triggered by cell-cell, cell-extracellular matrix (ECM), cell-cytokine interactions, and local microenvironment parameters are involved in controlling quiescence, self-renewal, differentiation, and migration of hematopoietic stem/progenitor cells (HSPC). A promising strategy to more efficiently expand HSPC numbers and tune their properties ex vivo is to mimic the hematopoietic niche through integration of adjuvant stromal cells, soluble cues, and/or biomaterial-based approaches in HSPC culture systems. Particularly, mesenchymal stem/stromal cells (MSC), through their paracrine activity or direct contact with HSPC, are thought to be a relevant niche player, positioning HSPC-MSC co-culture as a valuable platform to support the ex vivo expansion of hematopoietic progenitors. To improve the clinical outcome of hematopoietic cell transplantation (HCT), namely when the available HSPC are present in a limited number such is the case of HSPC collected from umbilical cord blood (UCB), ex vivo expansion of HSPC is required without eliminating the long-term repopulating capacity of more primitive HSC. Here, we will focus on depicting the characteristics of co-culture systems, as well as other bioengineering approaches to improve the functionality of HSPC ex vivo.

Interferon-Gamma-Mediated Osteoimmunology

“…Bone marrow is both a hematopoietic organ and an immune organ. In the bone marrow microenvironment, hematopoietic stem cells differentiate into erythrocytes, granulocytes, platelets, and all kinds of immune cells including monocytes, dendritic cells, T cells, B cells, and natural killer (NK) cells ( 6 , 7 ). Among them, the monocytes/macrophages from hematopoietic lineage are osteoclast precursors ( 8 , 9 ).…”

Antioxidant Small Molecule Compound Chrysin Promotes the Self-Renewal of Hematopoietic Stem Cells

“…For example, the latest discoveries are antagonist of PPAR-gamma GW9662 (Guo et al, 2018), inhibitor JNK-IN-8 (Xiao et al, 2019), and so on. Moreover, it is found that some co-culture systems or materials could provide a suitable microenvironment for HSC expansion, such as coculture with polyvinyl alcohol (PVA) (Wilkinson et al, 2019), zwitterionic hydrogel (Bai et al, 2019), or mesenchymal stem/ stromal cells (Costa et al, 2018). Since HSCs are deemed to grow in hypoxic environment (Takubo et al, 2010), low oxygen also plays an important role in the in vitro expansion of HSC.…”

Untitled

“…Вважається, що основні зміни клітинної композиції в органах імунної системи при стресі зумовлені перерозподілом мігруючих клітин і вираженістю апоптотичних процесів, які здійснюються в кістковому мозку і тимусі [16][17][18]. Мабуть, вирішальну роль у формуванні особливостей клітинних стресових реакцій і індукції регенерації імун ної системи відіграють гемопоетичні стовбурові клітини (ГСК) -родоначальники всіх гемопоетичних клітин, в тому числі тих, що є структурно-функціональною основою імунної системи [11][12][13]. Але зазначені питання слабо вивчені, хоча зрозуміло, їх висвітлення буде корисним і в теоретичному і практичному аспектах.…”