Stem Cell Factor

About SCF:

Stem cell factor is also known as SCF, KIT-ligand, steel factor or KL. It is a cytokine that binds to the c-KIT receptor (CD117). SCF can act as both a transmembrane protein and a soluble protein. It plays an important role in hematopoiesis (the formation of blood cells), melanogenesis and spermatogenesis.

Production
Stem cell factor is encoded by a gene found on the Sl locus in mice and on chromosome 12q22-12q24 in humans. The transmembrane and soluble forms of the protein are created by alternative splicing of the same RNA transcript. The soluble form of SCF contains a proteolytic cleavage site. Cleavage at this site allows the extracellular portion of the protein to be released. The transmembrane form of SCF is created by alternative splicing that excludes exon 6. Both forms of SCF bind to c-KIT and are biologically active. Soluble and transmembrane SCF is produced by fibroblasts and endothelial cells. Soluble SCF has a molecular weight of 18,5 kDA and forms a dimer. In normal human blood serum, it is detected at 3.3 ng/mL.

Developmental Role
SCF plays an important role in the hematopoiesis during embryonic development. AReas where hematopoiesis take place (for instance, bone marrow or the fetal liver) all express SCF. Mice that do not express SCF die in utero from severe anaemia. Mice that do not express the receptor for SCF (c-KIT) also die from anaemia. SCF could serve as guidance cues that direct hematopoietic stem cells (HSCs) to their stem cell niche and plays an important role in HSC maintenance. Non-lethal point mutants on the c-KIT receptor can also cause anaemia, decreased pigmentation and decreased fertility.

Hematopoiesis Role
SCF also plays a role in the regulation of HSCs in the stem cell niche in the bone marrow. Research has shown that HCF can improve the survival rate of HSCs in vitro and contributes to the maintenance and self-renewal of HSCs in-vivo. HSCs at all stages of development express the same levels of the receptor for SCF (c-KIT). The stromal cells that surround HSCs are a component of the stem cell niche and they release a number of ligands such as SCF.

Interactions
Research into stem cell factor has shown it to interact with mast/stem cell growth factor receptor (SCFR) or CD117, a receptor tyrosine kinase protein in humans that is encoded by the KIT gene.

Clinical Relevance
SCF can be used along with other cytokines to culture HSCs and hematopoietic progenitors. The expansion of these cells outside the body (ex-vivo) would allow advances in bone marrow transplantation where HSCs are transferred to a patient to re-establish blood formation. One of the problems with injecting SCF is that it activates mast cells, making it difficult to use for therapeutic reasons. SCF injections have shown to cause symptoms similar to allergies and the proliferation of mast cells and melanocytes. Cardiomyocyte-specific overexpression of transmembrane SCF boosts stem cell migration and improves cardiac function and animal survival after myocardial infarction.