ABCB5-positive Mesenchymal Stem Cells (ABCB5+ MSCs)
Mesenchymal stem cells (MSCs) are multipotent cells that can replicate as undifferentiated cells and can differentiate into various cell types including adipocytic, chondrocytic or osteocytic but also epithelial, myocytic, endothelial or neuronal cells.
MSCs have been studied and used for more than a decade in the field of regenerative medicine to treat various diseases. Their beneficial effects rely on three mechanisms of action:
- Immunomodulation: Interaction with macrophages, dendritic cells, NKT cells, T cells and B cells
- Paracrine effects: Secretion of cytokines, chemokines and soluble factors (e.g. VEGF, bFGF, SDF-12)
- (Trans-) Differentiation into various cell types including smooth muscle cells and endothelial cells during angiogenesis
Human MSCs are most commonly isolated from the mononuclear fraction of the bone marrow or from adipose tissue. However, other tissues contain convincing stem cell compartments as well.
A subpopulation of the dermal stem cell compartment comprises MSCs that express the peptide ATP-binding cassette B5 (ABCB5) on their surface. These ABCB5-positive (ABCB5+) MSCs exhibit immunomodulatory effects based on the secretion of anti-inflammatory cytokines like IL-1RA (Hoogduijn et al., 2010, Wang et al., 2017) as well as on the expression of the immune checkpoint molecule PD-1 (Schatton et al., 2015). Via these pathways ABCB5+ MSCs trigger switch from pro-inflammatory M1 to anti-inflammatory M2 macrophages and stimulate proliferation of regulatory T cells.
Several preclinical studies have shown that ABCB5+ MSCs, based on their anti-inflammatory, anti-fibrotic and pro-angiogenic properties, exhibit a strong regeneration potential.
ABCB5+ MSCs are found in the skin of healthy individuals of all ages. To isolate ABCB5+ MSCs, a highly specific and highly sensitive antibody was created (Frank et al., 2003), purified according to GMP (Good Manufacturing Practice) conditions and tested for viral contamination. TICEBA GmbH, the parent company of RHEACELL, has established a highly standardized process to obtain ABCB5+ MSCs from human skin biopsies, expand them to a high standard and specifically isolate them as high-purity population.
In a comprehensive preclinical study program, safety and local tolerability of ABCB5+ MSCs following subcutaneous, intramuscular and intravenous application has been demonstrated (Tappenbeck et al., 2019).