Autologous hematopoietic stem cell transplant

Can we restore the immune system in MS?

Hematopoietic stem cells (HSCs) are the “seeds” of the cells that are the building blocks of our blood and the immune system. In adults, these stem cells are located in the bone marrow, a complex soft tissue that is located in the cavities of especially large, flat bones. During our lives, a large number of HSCs differentiate continuously to replenish blood and lymph nodes. They also replace adult cells and cells that have been eliminated or lost at the end of their functional life or in some other way. HSCs are therefore essential for our development and for survival. The ability of HSCs to replenish the blood and immune system is a very useful trait for the treatment of certain disorders. By administering HSCs, there are a lot of new, healthy cells and can even be “saved” from a bone marrow error caused by marrow damage or exposure to radiotherapy or chemotherapy. In experiments, a single HSC has renewed the blood of a mouse, so that the mouse survived a lethal amount of nuclear radiation under normal circumstances!


HSCs in the hospital: hematopoietic stem cell transplantation
Today haematologists in hematopoietic stem cell transplantation (HSCT) regularly use HSC infusion to stimulate the production of blood cells in people who have had high doses of immunosuppressive radiation or chemotherapy, so that they increase in number again. Normally, HSCs are harvested by a bone marrow puncture where the stem cells are sucked up from the bone marrow of the hipbone. Or one stimulates the growth of the stem cells through which they end up in the peripheral blood. By administering a hormone that stimulates cell division, a number of HSCs will end up in the blood stream. The patient’s blood is placed in a cell separator where the HSCs are collected together with the white cells from the peripheral blood. This process is called leukopheresis. The HSCs can be further purified by selecting cells with the CD34 markers they carry on the cell membrane. Umbilical cord blood is also very rich in HSCs and has been used for hematopoietic transplantation in cancer and especially in children who did not have a matching bone marrow donor. The HSCs can be harvested from a patient and kept for later administration to the same patient after chemotherapy; this procedure is called autologous stem cell transplantation. A genetically “matching” donor can also be sought from the family members of the person or from a donor registry for bone marrow or umbilical cord blood; the transplantation of HSCs from another person is called allogeneic stem cell transplantation. Allogeneic or autologous HSCT have a different indication and all two are widely used for the treatment of blood cancer, lymphoma and bone marrow cancer. HSC transplantation has been a life-saving treatment for tens of thousands of people with leukemia, lymphoma, myeloma and other malignant tumors.


HCST for “repairing the immune system” 
After observing a remission in people with a disease such as, for example, cancer treated with HSCT, clinical trials that study the potential utility of HSCT in MS and other autoimmune diseases have been initiated. Because the chance of side effects and serious complications is higher in allogeneic transplants, these tests have been limited to autologous HSCT.


How does autologous HCST work in MS?
The lesions in MS have been infiltrated with blood-derived immune cells. Among these are also T and B lymphocytes that appear to attack and damage the myelin-producing cells. We do not know what causes this attack, but the process almost certainly relates to the incorrect functioning of the immune system. The aim of HSCT in MS is to purify the existing immune system with immunosuppressive chemotherapy and to regenerate a population of new, healthy immune cells by means of HSCT. This process is called, very ingeniously, “resetting of the immunological clock”. This means that in principle adult cells of the immune system that attack the brain can be eliminated and replaced with new, harmless cells. Recent research has shown that this “reset” of the immune system actually takes place and that the thymus (thymus), the organ where haematopoietic progenitor cells develop into adult T lymphocytes, is reactivated after HSCT. As a result, the number of T cells, including possibly “regulatory” T cells that suppress autoimmune attacks, increases.


What can HSCT do for people with MS? 
Anno 2016, hundreds of people around the world have undergone an autologous haematopoietic stem cell transplant. Although randomized controlled research, which accurately determines the effectiveness, has not yet been completed, the analysis of the results reported so far provides an indication of what can and can not be achieved with this treatment at the moment. First of all, HSCT has generally shown a positive effect on the suppression of inflammation and the development of new plaques as demonstrated by MRI in an average of 80% of patients. With a majority of treated people, the existing neurological limitation stabilized and improved. Although HSCs can basically transform into any progeny of a cell, including neural or myelin-producing cells,


For consideration
At the moment there is international scientific phase 3 research on nonmyeloablative autologous hematopoietic stem cell transplantation in (aggressive) relapsing remitting MS (RRMS) on the way. The immune system can thus be ‘reset’ by means of immune therapy and re-introduction of the body’s own stem cells. The ‘reset’ immune system is built up faster by means of the body’s own stem cells, reducing the risk of infections and complications and the MS disappears. The immune system is reduced to a moment before the MS originated. In addition, the stem cells may or may not partially repair the damage caused by the MS in the central nervous system. These results with an average success rate of 80% are based on more than 20 years of research and are the basis for the international research that takes place in the United States, England, Sweden, Russia and Brazil. Whether the treatment is a cure, we can not say with certainty yet. That is why research into this treatment is so badly needed. The results that have been researched and published scientifically in the past 20 years are so encouraging, however, that the scientists are discussing with each other about when you may consider MS as a cure.

Video: HSCT Treatment