Mesenchymal stem cells
Mesenchymal stem cells are a group of multipotent cells able to transform into various types of adult cells, such as fat cells, osteoblasts, chondrocytes, muscle and nerve cells. These cells have special immunomodulatory properties, that is those that have positive impact on immunity, regenerative processes and selected other immunological processes taking place in human organism during the rejection of a transplant. Additionally it was found that they have anti-aging and angiogenesis- promoting properties that allow to create new capillary blood vessels which is important for example in the wound healing processes.
Where in human body you can find mesenchymal stem cells?
Sources of mesenchymal stem cells in human body can be divided into two categories: those of adult, fully-formed stem cells and those arriving during childbirth. The former are localised for example in bone marrow, fat tissue or peripheral blood. Smaller amounts of them can be found in a tooth pulp, lungs or eyeball.
Mesenchymal cells coming from afterbirth tissue can be collected from e.g. a fragment of placenta, chorioamnion, amnion, amniotic fluid, and even umbilical cord blood. Mesenchymal stem cells of a perfect quality can be harvested from Wharton’s jelly found in a human umbilical cord. The latest research show clearly that Wharton’s jelly (an element of human umbilical cord) is today the best available source of mesenchymal stem cells because cells isolated from that tissue show increased level of multiplication at the same time preserving the optimum vitality as compared to stem cells collected from bone marrow, fat tissue or peripheral blood.
Properties of human mesenchymal stem cells
Human mesenchymal stem cells have a set of unusual properties which make scientists and doctors all over the world use them as experimental therapeutic material. These scientifically proved properties, are the following:
- Self-renewing (proliferation) – ability to limitless cell division within a given stem cell culture. It means that cells that have such a property will never lose their “stem” nature and will always start new cell generations during each, cyclical cell division.
- Differentiation – allowing them to transform into other cell structures, often fully functional. Mesenchymal stem cells can differentiate (transform) among other things into osteoblasts, chondrocytes, fat, skeletal muscle, heart muscle and nerve cells.
- Immunosuppressive/immunomodulatory – consisting in immunological response, activated by the organism in the case of for example placing a foreign body through its grafting (transplantation). Mesenchymal stem cells inhibit or modify immunological cells operation taking part in responding to the transplantation thus preventing the graft rejection.
- Anti-aging (antiapoptotic) – mesenchymal cells are able to “save” healthy cells from death if they are damaged due to harmful effects of radiation, hypoxia, chemicals or mechanically damaged.
- Angiogenic (neovascular) – allowing to secrete chemical compounds stimulating creation of new blood vessels. It is important especially in the process of wound healing as well as in reconstruction of damaged tissue.
- Antimicrobiological (antibacterial, antiprotozoal) – allowing to secrete the same or similar compounds to those secreted by cells of the immune system while combatting pathogens present in the body. Mesenchymal stem cells secrete compounds supporting the immune response to bacteria and parasites.
- Anti-inflammatory – inhibiting inflammation processes by secreting anti-inflammatory factors. Thus mesenchymal stem cells inhibit activity of the immune system cells and slow down the development of inflammatory condition.
- Regenerative – that allow to move and find a site of damaged and promote activation of the regenerative processes and increasing their efficiency.
Therapeutic indication for human mesenchymal stem cells use
Mesenchymal stem cells are currently intensely tested for their use in regenerative medicine/cell therapy. For a dozen or so years, it has been repeatedly confirmed that mesenchymal stem cells obtained for example from the bone marrow are effective and safe in therapy of difficult cases of leukaemia, graft-versus-host disease and in other applications, such as curing of the wounds, burns, joint damages as well as aesthetic medicine. One of the possible use of mesenchymal stem cells isolated from Wharton’s jelly is for adjunctive therapy in patients suffering from SLA.
Stem cells can be derived from the patient’s own tissue (bone marrow, fat) or obtained from a donor. In the case of Therapy carried at the Cell Therapies Institute stem cells will be harvested from so-called Wharton’s jelly. It’s a gelatinous substance within the umbilical cord rich in mesenchymal stem cells (WJ-MSC), a tissue surrounding umbilical vessels.
These cells can differentiate into many types of specialised cells. The properties of WJ-MSC are similar to those of mesenchymal stem cells obtained from other sources, with some advantages, as the cell-cycle time of cells isolated from Wharton’s jelly is shorter and they proliferate for longer period in a cell culture than it is in the case of e.g. BMSC (stem cells derived from bone marrow). It is also much easier to obtain WJ-MSC than mesenchymal stem cells derived from bone marrow or fat, as WJ-MSC are isolated from an umbilical cord which until recently was normally disposed of. The cell isolation process is not painful, does not give rise to any ethical conflicts. Also, WJ-MSC have no tumorigenic properties, as is in the case of embryonic stem cells (ESC).
Like mesenchymal cells isolated from other tissue, WJ-MSC can differentiate into osteoblasts, adipocytes, chondrocytes, endotheliocytes, myocytes and cardiomyocytes in an in vitro culture. Moreover, WJ-MSC cells show the ability to transform into nervous tissue cells, that is dopaminergic neurons, cholinergic neurons, Schwann cells that produce myelin sheath and oligodendrocytes. In the pre-trial study of the induced stroke in rats, the WJ-MSC introduced into the rat’s brain differentiated in vivo into endothelial cells and neurons. Thus WJ-MSC implantation can potentially contribute to repair of the nervous system tissue through direct differentiation of stem cells into specialised cells allowing to replace the neurons or oligodendrocytes damaged by a disease. Moreover WJ-MSC cells have also the ability to produce proteins which are secreted into the extracellular space and stimulate tissue regeneration. Among others, WJ-MSC produce angiogenic factors such as CXCL2, CXCL5 and FGF9 as well as neurotrophic factors NTF3, EGF and MDK. Expression of the above-mentioned neurotrophic factors is higher in WJ-MSC as compared to BMSC. An in vitro trial showed that paracrine factors produced by WJ-MSC increase the survival rate and primary division of cortical and cerebellar neurons.
Another WJ-MSC characteristics, important for the clinical use, are its immunomodulatory properties, that is their abilities to inhibit activation of the immune system. The laboratory tests showed that WJ-MSC inhibit proliferation of stimulated splenocytes and T lymphocytes and that they themselves do not stimulate T lymphocytes proliferation. Furthermore, WJ-MSC present low expression of CD40, CD80 and CD86 costimulatory receptors on T lymphocytes and high expression of proteins showing immunosuppressive properties- HLA-G, IL-6, VEGF. In other works it was pointed to inhibition of differentiating monocytes into dendrite cells and inhibition of TNF and IFN pro-inflammatory factors by stimulated T lymphocytes.
Numerous effective use of mesenchymal stem cells in haematology, oncology and for transplantation purposes has already been described in among other things:
- prophylaxis of graft versus host disease (GvHD)
- treatment of acute graft versus host disease (aGvHD)
- treatment of chronic graft versus host disease (cGvHD)
- reconstruction of autologous haematopoietic system
- reconstruction of the recipient’s haematopoietic system using the allogeneic hematopoietic stem cells
- treatment of toxicity caused by chemotherapy and radiotherapy.