23 August 2016

Bone marrow transplantation without chemo and radiotherapy

Hematopoietic (hematopoietic) stem cell transplantation, commonly known as bone marrow transplantation, is an effective approach that potentially provides a cure for a number of diseases, including malignant diseases of the circulatory system, as well as autoimmune and hereditary diseases.

For successful transplantation of hematopoietic stem cells, it is necessary to destroy the patient's own population of these cells. Currently, chemo or radiotherapy is used for this. Both of these approaches are very toxic and can cause damage to various organs and tissues, including the liver, reproductive organs and brain. This leads to both immediate and delayed problems, including seizures and disorders of growth and neurological development in children. For this reason, hematopoietic stem cell transplantation is performed only in cases where the risks associated with the disease exceed the risks of complications of transplantation.

Researchers at Stanford University, working under the guidance of Professor Judith Shizuru, have developed an approach in experiments on mice that significantly reduces the toxicity of this therapy.

To avoid side effects, the researchers used a combination of biological methods that made it possible to transplant hematopoietic stem cells without prior chemo and radiotherapy.

First, they used antibodies to the c-kit cell surface antigen, which is the main marker of hematopoietic stem cells. The introduction of this antibody drug ensured the destruction of hematopoietic cells in the body of immunodeficient mice. In order to destroy hematopoietic cells in animals with a normal immune system, antibodies against c-kit were combined with a biological agent blocking another cell surface protein known as CD47. This facilitated the absorption of antibody-coated c-kit cells by macrophages.

Comparing the transplantation of hematopoietic stem cells with the sowing of a new culture in the field, Professor Shizuru noted that her group had not only developed a new method of "weeding" the field, but also applied a method of introducing new cells that increases the safety of the procedure. Currently, the transplant is a mixture of cells, in addition to hematopoietic cells containing various immune cells of the donor, often beginning to attack the recipient's tissues. This immune reaction, known as the "graft versus host" reaction, can lead to damage to various tissues and even death of the patient.

Using the previously developed approach, the authors purified the donor material in such a way that at the time of transplantation it contained only hematopoietic stem cells and did not contain immune cells that cause a "graft versus host" reaction.

The successful application of this technology in experiments on mice gives hope for the possibility of its application in clinical practice. If successful, this will reduce mortality during hematopoietic stem cell transplantation from 20% to 0%.

The possibility of replacing the hematopoietic and immune systems safely for the patient will allow to cure autoimmune diseases such as rheumatoid arthritis and type 1 diabetes mellitus by getting rid of aggressive immune cells that damage their own tissues.

The approach proposed by the authors can also be used to improve the safety of organ transplantation. Currently, recipients of donor organs are forced to take immunosuppressive drugs for the rest of their lives that prevent the immune system from attacking donor organs. However, even against the background of taking immunosuppressants, in most cases, such patients develop insufficiency of transplanted organs, requiring repeated transplantation. In addition, immunosuppressive drugs increase the susceptibility of patients to life-threatening infectious diseases and the risk of developing malignant tumors.

Theoretically, with simultaneous transplantation of a donor organ and hematopoietic stem cells from the same donor, the patient's new immune system will not attack the transplanted organ, which, provided that hematopoietic cell transplantation is safe, will expand the possibilities of organ transplantation.

Article by Akanksha Chhabra et al. Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy is published in the journal Science Translational Medicine.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Stanford University School of Medicine: Researchers develop a method for bone marrow transplants without using chemotherapy.


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