Cord Blood Stem Cells Expansion Using Notch Signaling
Notch signaling in cord blood stem cells
Transplantation of the human umbilical cord blood transplantation (UCBT) often results in delayed engraftment due to the low level of stem cells available (Hofmeister, Zhang, Knight & Stiff, 2007). Expansion of the Hematopoietic stem cells (HSC) present in the umbilical cord is hence of essence. Prior efforts to expand the HSC ex vivo resulted in mature cells rendering it less effective. Notch signaling has shown the ability to expand HSC cells resulting in their immature daughter cells. Notch plays a crucial role in hematopoiesis, the transition of epithelial to mesenchyme and apoptosis (Hofmeister, Zhang, Knight & Stiff, 2007). Moreover, the Notch is essential in differentiation and proliferation of cells (Hofmeister et al. 2010; La Motte-Mohs, Herer & Zúñiga-Pflücker, 2005). Delany et al. (2010) states that the expression of an active form of the notch1 results to self-renewal of repopulating cells. Notch signaling in cord stem cell expansion shows an advantage over the ex vivo methods due to the ability of the resulting cells to promote apoptosis, cell cycle initiation and disrupt marrow homing.
Dahlberg, Delaney and Bernstein (2011) argues that Notch signaling is activated by ligand binding to an receptor extracellular domain (Karanu et al., 2000). The extracellular domain (ECD) of the receptor is responsible for protecting transmembrane from undergoing proteolytic cleavage. The binding of the ligand results in proteolytic cleavage events that expand the HSCs. The concept of the receptor-ligand binding can be used to allow for the expansion of the HSC. According to Delaney, Ratajczak and Laughlin (2010), exogenous ligands can be used to activate the Notch signaling pathway. Upon activation by a relevant ligand, the notch signaling process allows for stem cell renewal while inhibiting their differentiation (Varnum-Finney et al., 1998). The renewed cells are immortal and act as hematopoietic precursors.
Various challenges face cord blood stem cells expansion. Different methods have been set and examined for their effectiveness in the expansion of this cell line. Ex vivo expansion has been suggested to reduce the time required for engraftment and immune reconstitution. However, there is still need for the use of double cord blood transplants in treatment.
References
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