Microarray profiles of ex vivo expanded hematopoietic stem cells show induction of genes involved in noncanonical Wnt signaling

Abstract

ABSTRACT. The low number of hematopoietic stem cells (HSC) in umbilical cord blood (UCB) is directly related to increased risk of transplant failure. Effective ex vivo expansion of HSC has been tried for many years, with conflicting results because of the inability to reproduce in vitro HSC proliferation in the same way it occurs in vivo. We compared freshly isolated HSC with their expanded counterparts by microarray analysis and detected activation of the noncanonical Wnt (wingless-type MMTV integration site family) pathway. Study of early alterations during ex vivo UCB-HSC expansion could contribute to improvement of ex vivo expansion systems.

Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic Stem Cells

“…Since Wnt induces HSPC self-renewal in some organs, it enables the in vitro expansion of such cells and maintains their potency to reconstitute the entire cells after transplantation. 17,18 Hedgehog signaling pathway modulates the transcription of target genes that affect the quiescence, self-renewal, proliferation, and differentiation of HSPCs. Three distinct ligands, i.e.…”

“…16 HSPCs are increasingly used for‏ allogeneic and autologous transplantation but recovery of platelets occurs with a lower rate; therefore, several studies have shown that the proliferation of HSPCs in vitro could result in faster recovery after transplantation. 17,18 MSCs release many growth factors that stimulate hematopoiesis, prepare a scaffold for hematopoiesis, protect primitive progenitor cells, expand and maintain HSPCs in LTBMC with CD34 hematopoietic progenitor cells (HPCs), supporting both erythroid and myeloid differentiation. 19 …”

The Interaction Between Niche and Hematopoietic Stem Cells

“…It was demonstrated that both LRP-5/6 and Frizzled are required to activate functionally the downstream components of the canonical pathway. By now we know there are 19 secreted Wnt ligand glycoproteins, 10 Frizzled receptors, and 2 LRP coreceptors [25][26][27]. At least three different Wnt pathways are currently recognized: the canonical Wnt pathway, the non-canonical Wnt pathway and the planar cell polarity(PCP) pathway.…”