Stem cells are a special type of cells, and can be found in the embryo, in the developing animal, and also in adult tissues. Stem cells are characterized by the capacity to generate differentiated cells with specialized functions and to self-renew, producing more stem cells. Embryonic stem cells play an important role in the development of multicellular organisms, producing all cell types required in the later adult tissues. Adult stem cells reside in most of adult tissues and are known to play an important function in cell replacement, repair and regeneration of tissues upon tissue wearing, aging, injury or disease. Adult mesenchymal stem cells (MSCs) are found in tissues of mesodermal origin such as bone marrow, adipose tissue, placenta, umbilical cord, dental pulp or the synovium. MSCs can differentiate to cell types of the mesodermal lineage, mainly adipocytes, osteocytes and chondrocytes. Adipose tissue is an excellent source of MSCs because subdermal fat is easy to obtain and contains a significantly higher proportion of MSCs compared to other sources such as bone marrow. MSCs are considered a promising tool for cell therapy in regenerative medicine as well as for treating inflammatory diseases based on their differentiation capacity, the release of trophic factors with anti-fibrotic, anti-apoptotic or pro-angiogenic properties and their capacity to modulate the immune response.
MSCs show immunomodulating properties and regulate the function of a broad number of immune cells including B lymphocytes, T lymphocytes, macrophages and NK cells. The molecular and cellular mechanisms involved in the immunoregulatory activity of MSCs rely on cell-to-cell interactions, soluble factors and through the generation of cells with regulatory activity, such as regulatory T lymphocytes or anti-inflammatory macrophages, which play a central role in maintaining an appropriate balance of the immune system in health and disease. In addition, MSCs have also been reported to show antimicrobial activities against different pathogens.
THERAPEUTIC USE OF ADULT STEM CELLS
Stem cells can be used for potential treatment of a number of diseases taking benefit of their different functionalities. As such MSCs are defined as autologous, when isolated from a given patient and re-used to treat the same patient. They are defined as allogeneic when isolated from a healthy donor and being used in a different person. This latter use is possible since MSCs are considered to be low immunogenic and can thus be administered without the requirement of immunosuppressants. Allogeneic MSCs are regarded as a preferred source for treatment as they would allow treatment with a ready to use, off-the-shelf product, available for a large number of patients, specially, in acute life threatening indications like sepsis in which isolation and expansion of autologous MSCs is not an option.
One potential therapeutic application of MSC’s is the repair and/or regeneration of injured or dysfunctional tissues. Based on their capacity to self-renew and to differentiate into different cell types, MSC carry indeed the potential to restore the structural tissue and its functionality. Several clinical trials in e.g. cardiac repair, diabetes or neurological diseases are currently ongoing.
The other therapeutic potential of human MSCs is in the fields of inflammation control and auto-immunity modulation. Such therapeutic benefit has already been reported in a number of experimental models of inflammatory diseases such as allograft rejection, graft-versus-host disease, collagen-induced arthritis, colitis and sepsis. In experimental models of sepsis, MSC treatment modulates inflammation in by a mechanism that requires the reprogramming of macrophages towards a more anti-inflammatory phenotype (release of anti-inflammatory IL10), resulting in reduced levels of pro-inflammatory cytokines in blood and organs and attenuated infiltration of immune cells in infected tissues (monocytes and neutrophils). Moreover, MSCs show direct (release of LL-37 peptide) and indirect (increase of phagocytic properties of monocyte/macrophages and neutrophils) anti-microbial effects. The combined effect of reducing both the inflammatory response and the bacterial burden results in an improvement of organ function and higher survival rates. The promising results obtained in these preclinical efficacy studies are encouraging and suggest that MSCs might be a therapeutic option to treat sepsis in patients.
LINKS OF INTEREST