Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells from Umbilical Cord Blood

Abstract

Transplantation of umbilical cord blood cells is currently widely used in modern cell therapy. However, the limited number of hematopoietic stem and progenitor cells (HSPCs) and prolonged time of recovery after the transplantation are significant limitations in the use of cord blood. Ex vivo expansion with various cytokine combinations is one of the most common approaches for increasing the number of HSPCs from one cord blood unit. In addition, there are protocols that enable ex vivo amplification of cord blood cells based on native hematopoietic microenvironmental cues, including stromal components and the tissue-relevant oxygen level. The newest techniques for ex vivo expansion of HSPCs are based on data from the elucidation of the molecular mechanisms governing the hematopoietic niche function. Application of these methods has provided an improvement of several important clinical outcomes. Alternative methods of cord blood transplantation enhancement based on optimization of HPSC homing and engraftment in patient tissues have also been successful. The goal of the present review is to analyze recent methodological approaches to cord blood HSPC ex vivo amplification.

Cytokine Storm Combined with Humoral Immune Response Defect in Fatal Hemorrhagic Fever with Renal Syndrome Case, Tatarstan, Russia

“…These cytokines have pleiotropic effects linked to stem cell proliferation, mononuclear leukocyte chemotaxis and inflammation; however, one shared feature is that these cytokines target mononuclear leukocytes. SCGF-b triggers proliferative activity of hematopoietic progenitor cells [28] and, together with Flt-3 Ligand and VEGF, it can promote the CD34 + CD133+ progenitors expansion and differentiation into the endothelial cells [29,30]. TNF-β plays a central role in establishing lymphoid microenvironments, host defense and inflammation.…”

Influence of the mesenchymal stromal cell source on the hematopoietic supportive capacity of umbilical cord blood-derived CD34+-enriched cells

“…It was suggested that this better support could be attributed to chemokine CXCL12, a critical regulator of hematopoiesis, found to be expressed threefold higher in AT MSC than BM MSC [ 61 , 62 ], even though less than 1% of genes were found to be differentially expressed between AT and BM MSC [ 63 ]. By seeding UCB MNC upon an AT MSC FL and making successive removals of non-adherent cells, Andreeva and colleagues [ 64 ] were able to verify that AT MSC enabled the selection of functionally active CD34 + HSPC at normoxia (20% O 2 ) and hypoxia levels (5% O 2 ) after 7 days of expansion. Even though they used an interesting strategy to enrich CD34 + cells during culture, their expansion levels were quite low (6-10x) compared to our FI of CD34 + cells (60x), which can easily be explained by their lack of exogenous cytokines besides using an expansion system that still relies on FBS usage.…”

A new beginning: can omidubicel emerge as the next, viable alternative donor source?

“…Finally, homing strategies to enhance UCB function include dipeptidyl peptidase 4 inhibition, complement fragment 3a priming, increase in CXCR4 via dimethylprostaglandin E2 pathway, and fucosylation of cell surface molecules required for P-and E-selectin binding. 16,39,40 Successful use of ex vivo expanded UCB requires effective expansion of the hematopoietic progenitor cells as well as stem cells, while maintaining their capacity for homing as well as for short and long-term engraftment. Graft manipulation strategies with UCB focus on these main aspects of CBT and omidubicel has shown the most success with adequate data to support progression to the recent completion of a randomized phase 3 study.…”