The immune system is the body’s defense mechanism against foreign agents that invade it, including infectious organisms. A properly functioning immune system must effectively differentiate the cellular constituents of its own body from those of an invading organism that should be attacked while those of its own body should not. This is how the immune system defends the body from pathogens.
An infection will occur if the immune system does not quickly detect and eliminate the foreign organism. Another problem will arise if the immune system mistaken its own body’s cellular components for an invading organism and subsequently attacks them – this problem is known as an autoimmune disease.
Image 1. How the immune system responds to self or foreign antigens.
The failure of the immune system to make a proper distinction between its body’s cellular components and a foreign organism is what leads to kidney damage in systemic lupus erythematosus (SLE) and joint damage in rheumatoid arthritis (RA). Other common autoimmune diseases include multiple sclerosis (MS), type 1 diabetes, Sjogren’s syndrome and inflammatory bowel disease.
The cause of this self-destroying behavior of the immune system is not fully known, although, some genetic, hormonal and environmental factors and infections may contribute to autoimmune disease development in patients.
WHAT IS STEM CELL THERAPY?
The current procedures for treating a lot of autoimmune diseases involve systematically using anti-inflammatory medications and potent immuno-modulatory and immunosuppressive agents such as steroids and inhibitor proteins that antagonize the activities of inflammatory cytokines. Although these therapies have had some significant effects in correcting immune responses, they still do not work in the treatment of certain patients and may have unpleasant side effects.
According to Wikipedia, stem cell therapy is the administration of stem cells (SCs) to treat or prevent a disease condition. SC transplants have been used for decades in patients with leukemia, lymphoma and other hematologic cancers to help reconfigure their immune systems. Researchers then wondered if the diseases helped by stem cells could be extended to include autoimmune diseases.
Image 2. Application of stem cells.
Much extensive research on stem cells and disease treatment of an autoimmune nature were conducted, and many leading health centers providers offer patients the most effective procedures that are scientifically proven.
HOW STEM CELLS CAN TREAT AUTOIMMUNE DISEASES
The first accepted stem cell therapy for autoimmune disease which is known as hematopoietic stem cell transplantation (HSCT) is a series of treatment procedures aimed at resetting the dysfunctional immune system of patients who are suffering from severe autoimmune diseases.
Almost every stem cell transplant for autoimmune diseases involves using the patient’s own (autologous) stem cells. Once proven to be effective, this type of stem cell transplant for autoimmune disease will be accessible to many patients, since the need to search for a matching stem cell donor would have been eliminated.
Currently, adult patients are getting SCs for autoimmune diseases treatment from their own bone marrow (BM) or peripheral blood but at the rate at which studies are advancing, children of today could undergo analogous transplants using their own umbilical cord blood in the eventuality that they develop an autoimmune disorder later in their lives.
Asides eliminating the need to search for a matching donor, autologous HSCs require lower levels of chemotherapy treatment which helps to reduce the risk of the patient developing life-threatening complications.
Most of the time, the treatment procedures for autologous HSCT involve three major steps and they are:
1. Using bolus infusions of cyclophosphamide (CY) plus subcutaneous injections with granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood progenitor cells.
2. Conditioning – this involves subjecting the patient to high doses of chemotherapy or total body irradiation (TBI).
3. Reinfusing the graft product which may or may not involve ex-vivo manipulation.
Since HSCT causes many side effects, some treatment protocols have been developed using only mesenchymal stromal cells, without the application of chemotherapy. This is a more gentle treatment, which also allows you to get a pronounced result without causing damage to the body.
EMBRYONIC AND ADULT STEM CELLS
SCs are known for their ability to self-renew, proliferate and mobilize. Their other characteristics include multilineage differentiation and homing. They are of two main groups:
1. Embryonic stem cells (ESCs). When they are obtained approximately three days following fertilization, they are totipotent, which means they can produce more than 200 cell-types including extra-embryonic tissues like the placenta and umbilical cord. ESCs obtained four or five days after fertilization are pluripotent, which means they are capable of producing all cell-types except for extra-embryonic tissues.
2. Adult stem cells (ASCs). They most times produce specific tissue progenitor cells. They are most times multipotent, that is, the number of cell-types they produce is more limited. HSCs are one of such multipotent ASCs and they in turn produce all blood cell-types and immune SCs. The bone marrow, adipose tissue and umbilical cord blood are the major sources of HSCs, although they may also be found in peripheral blood albeit at smaller quantities. Also, peripheral SCs like mesenchymal stem cells (MSCs) and multipotent adult progenitor cells have been discovered in many adult tissues. This type of stem cell is widely used for cell-based therapy at regenerative medicine centers, such as Swiss Medica in Europe and others.
WHAT DO WE KNOW ABOUT MSCs FOR AUTOIMMUNE DISEASES
More and more evidence suggest that the immuno-modulatory properties of MSCs are responsible for their therapeutic effects. The micro-environmental inflammatory conditions determine how MSCs regulate their immuno-modulatory functions. The anti-inflammatory and immuno-modulatory effects of MSCs are seen in the regulation of lymphocytes of innate and adaptive immune systems.
An increasing number of evidences also suggest the following about MSCs:
- MSCs can modulate the proliferation and function of T cells.
- They can regulate the activities of T-helper 1 (TH1) and T-helper 2 (TH2).
- The functions of regulatory T cells can be upregulated by MSCs.
- MSCs can repress the functions of B cells.
- The proliferation and functions of natural killer cells can be impeded by MSCs.
- MSCs block the maturation and activation of dendritic cells.
- MSCs can facilitate the secretion of cytokine and proliferation in innate lymphoid cells.
Considerable research has been done in clinical medicine concerning the human stem cell and disease conditions of an autoimmune nature. The current options of therapy for treating three types of autoimmune diseases is discussed below.
Stem Cell Therapy for Lupus
Evidence suggests that in patients with systemic lupus erythematosus, there is bone marrow dysfunction with a notable decrease in the number of CD34+ cells and also a possibility of a reduction in the proliferation capability of the SCs. There are also increased levels of CD34+ subpopulation apoptosis and a reduction in the frequency of colony-forming units when in comparison with control groups.
According to a report, between 1995 and 2002, the European Society for Blood and Marrow Transplantation (EBMT) and European League against Rheumatism (EULAR) reported using HSCT for 53 registered cases of lupus. Between 1997 and 2005, a transplant center in the US also had 50 patients undergo HSCT. The current procedure for stem cell treatment for lupus involves using CY and G-CSF for mobilization and high levels of CY doses and antithymocyte globulin (ATG) coupled with CD34+ selection in vitro. 32 other isolated cases have been reported besides the EBMT/EULAR and American studies. There were 22 cases where clinical remission occurred with the treatment using stem cells and lupus relapse occurred in about 30% of these cases.
What was found out with the use of stem cells for lupus was that the risk of relapse increased with the length of the post-transplantation period. It was also found out that there was no detectable difference in relapse frequency with CD34+ selection or with more intense conditioning.
Also, the lupus stem cell treatment does not come with severe adverse effects and therapies to which patients have been known to be previously resistant can be used to control the disease’s activity. These findings suggest promising results in cases of patients suffering from lupus and stem cells are used for their treatment.
Stem Cell Therapy for Multiple Sclerosis
Multiple sclerosis, an organ-specific autoimmune disease, is mediated by T-cells that attack the structural components of myelin in the central nervous system (CNS). In this disease, there is an interruption of an electrical signal which is a result of demyelination and loss of axons that comes after inflammation in the CNS.
There are no available curative treatments for multiple sclerosis. Treatments are only able to reduce CNS inflammation and delay disease advancement. The immuno-suppressive and immuno-modulatory actions of analogous HSCT are what multiple sclerosis stem cell therapy is based on. Multiple sclerosis is a multifocal disease and this makes injecting SCs into each affected site practically impossible, meaning that these cellular entities have to be attracted to the pathological locations after their introduction to the patient’s body.
There is an alternative procedure of stem cell therapy multiple sclerosis can be treated with. It involves the intravenous administration of mesenchymal stem cells. Also, stem cell research for multiple sclerosis indicates that these cellular entities are able to reach the CNS and transdifferentiate or acquire properties of oligodendrocytes and possibly neurons – this provides a possibility that may be effective in the repair of neurons and also re-myelinization.
Stem Cell Therapy for Rheumatoid Arthritis
Rheumatoid arthritis is a systemic autoimmune disease that can cause irreversible damage to the joints, mobility loss, the need for surgery, and quality of life reduction. Lesions develop as a result of cellular and humoral immune responses. In 80% of rheumatoid arthritis patients, an autoantibody specific to the Fc region of the human immunoglobulin G can be found. This autoantibody is called the rheumatoid factor.
Image 3. Local injection during stem cell therapy for rheumatoid arthritis.
A suitable technique in stem cell treatment for rheumatoid arthritis is the mobilization of HSCs with G-CSF. Administering cyclophosphamide before G-CSF has been shown to be somewhat advantageous. Inducing immunosuppression by CY may help decrease the risk of triggering more symptoms of rheumatoid arthritis that is produced by G-CSF. Cyclophosphamide appears to increase HSC levels, aid graft manipulation, while also decreasing the amount of T lymphocytes re-introduced into the system which are potentially pathogenic.
It also seems to facilitate the repair of immuno-competent cellular entities and reestablish the immuno-logical balance without the need to re-infuse HSCs into the patient.
The efficiency of current immunosuppression-based therapies for autoimmune diseases is not too high, and emerging disease-modifying drugs fail to stop the progression of the degenerative processes, in addition to the destructive effect on the entire body. Intravenous and/or local stem cell introduction as an alternative treatment option may lead to a better result.
WHAT GOALS CAN BE ACHIEVED WITH CELL THERAPY?
Cell treatment for autoimmune diseases provides immunosuppressive and immuno-modulatory effects in patients. The use of a stem cell for autoimmune disease treatment helps to restore the dysfunctional immune system. The lymphatic system will be renewed and the diseases’ activities will be reduced which will result in long-term remission.
MSCs offer a positive outlook in the therapy for autoimmune diseases. It is reported that the treatment brought about by these cellular entities may allow for the production of immunosuppressive factors and may help in the repair of tissues damaged by the chronic inflammatory process.
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