Human Adipose-Tissue Derived Stromal Cells in Combination with Hypoxia Effectively Support Ex Vivo Expansion of Cord Blood Haematopoietic Progenitors

Abstract

The optimisation of haematopoietic stem and progenitor cell expansion is on demand in modern cell therapy. In this work, haematopoietic stem/progenitor cells (HSPCs) have been selected from unmanipulated cord blood mononuclear cells (cbMNCs) due to adhesion to human adipose-tissue derived stromal cells (ASCs) under standard (20%) and tissue-related (5%) oxygen. ASCs efficiently maintained viability and supported further HSPC expansion at 20% and 5% O2. During co-culture with ASCs, a new floating population of differently committed HSPCs (HSPCs-1) grew. This suspension was enriched with СD34+ cells up to 6 (20% O2) and 8 (5% O2) times. Functional analysis of HSPCs-1 revealed cobble-stone area forming cells (CAFCs) and lineage-restricted colony-forming cells (CFCs). The number of CFCs was 1.6 times higher at tissue-related O2, than in standard cultivation (20% O2). This increase was related to a rise in the number of multipotent precursors - BFU-E, CFU-GEMM and CFU-GM. These changes were at least partly ensured by the increased concentration of MCP-1 and IL-8 at 5% O2. In summary, our data demonstrated that human ASCs enables the selection of functionally active HSPCs from unfractionated cbMNCs, the further expansion of which without exogenous cytokines provides enrichment with CD34+ cells. ASCs efficiently support the viability and proliferation of cord blood haematopoietic progenitors of different commitment at standard and tissue-related O2 levels at the expense of direct and paracrine cell-to-cell interactions.

Hypoxia Enhances Mesenchymal Characteristics Maintenance of Buffalo Bone Marrow-Derived Mesenchymal Stem Cells

“…In this study, we found that hypoxia contributed to maintaining the morphology of bBMSCs at passage 10, indicating that hypoxic conditions presented herein suitably replicates in vivo physiology. These results are in agreement with the finding of other researchers who reported the effects of hypoxia on MSCs (Andreeva et al, 2015;Deng et al, 2019).…”

Co-Transplantation of Hypoxia Pretreated Human Adipose Derived Mesenchymal Stem Cells and Cord Blood Mononuclear Cells to Treat Rats With Acute Myocardial Infarction

“…ASCs would support other types of cells (e.g. HSPCs) for their viability and proliferation, through direct/ paracrine cell-to-cell interactions [34,35]. In addition, ASCs can also upregulate the adhesion molecule and extracellular matrix genes in HSPCs, which was good for the latter to anchor and survive in the local area [36].All aforementioned evidence demonstrated that the paracrine factors that secreted by ASCs might be used by CBMNCs for survival and function when they are co-transplanted simultaneously.…”

Obstetrical and neonatal factors associated with optimal public banking of umbilical cord blood in the context of delayed cord clamping

“…Reduced pH of umbilical cord venous blood is commonly associated with variable degrees of neonatal distress that can include neonatal hypoxia and/ or physiologic stress on the placental vasculature. Hypoxia has been previously associated with hematopoietic progenitor expansion in laboratory studies [13][14][15]. Indeed, the bone marrow stem cell niche is a relatively hypoxic environment [18] and inflammatory cytokines released during physiologic stress [19] or physical exercise [20] and can induce expansion and mobilization of progenitors.…”

“…In particular, DCC may not be performed in cases associated with infant distress or the need to perform urgent interventions for the baby or mother. The hypoxic stress that is associated with a proportion of such deliveries may actually mobilize greater numbers of stem and progenitor cells [13][14][15]. In this study, we assessed whether specific newborn and maternal factors correlated with indicators of increased blood-forming capacity to inform strategic collection strategies that could augment the quality of units in public cord blood banks.…”