Mimicking Key Cytokines TPO and SCF in the Production of Mature Blood Cells from Haemotopoietic Stem Cells (#30)
Haematopoiesis is the process by which all blood cellular components are formed from haematopoietic stem cells (HSCs) located in the bone marrow. HSCs are self renewing and have the unique ability to give rise to all the different mature blood cell types and tissues. In typical healthy adults, approximately 1011-1012 new blood cells are produced daily to maintain steady circulation. Blood-cell production is tightly regulated involving interactions between cytokines presented by the HSC microenvironment and their corresponding receptors on the HSCs. Approximately 60 cytokine/growth factors regulate aspects of haemotopoiesis, a small number of which are frequently included as soluble proteins in media for HSC expansion.
Recently, effort has focussed on developing mimics of these growth factors and their subsequent immobilisation onto surfaces, equivalent to how they are presented in the stem cell niche of bone marrow, for constructing bioinspired materials and HSC cultures systems for use in haemopoietic stem cell transplantation therapy.1,2
Two key primary stimulators of the HSC proliferation process are thrombopoietin (TPO) and Stem Cell Factor (SCF). Here we present our efforts towards developing short peptides (approx 20-30 aa) as mimics of these factors in the production of mature blood cells.
We demonstrate that a short peptide TPO mimetic can replace native TPO in stimulating the proliferation of HSCs in culture. We also demonstrate that this peptide can be immobilised on a gold-based self assembled monolayer (SAM) and maintains its integrity while supporting repetitive culture of factor dependent mpl cells for up to 14 days. In addition, we present our initial efforts towards the development of a helical peptide SCF mimetic.
These efforts will enable a greater understanding of the processes occurring within the HSC niche and lead to new technologies for cost effective and efficient generation of HSCs for use in haematopoietic stem cell transplantation therapies.
- ChemMedChem, 2013, 8, 763
- Cytokine & Growth Factor Reviews, 2011, 22, 231.