Cell therapy of Parkinson's disease is getting closer to people
Comparative studies on primates have shown the prospects of transplantation
dopaminergic neurons derived from IPSC
LifeSciencesToday based on the materials of the Center for iPS Cell Research and Application:
Direct Comparison of Autologous and Allogeneic Transplantation of iPSC-Derived
Neural Cells in the Brain of a Nonhuman Primate
Induced pluripotent stem cells (iPSCs) obtained from mature patient cells have great therapeutic potential in many diseases. However, studies on rodents have shown that the body can respond to the transplantation of such cells or their derivatives with an immune rejection reaction and destroy them. A new study on monkeys, the results of which are described in an article published in the journal Stem Cell Reports (Morizane et al., A direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate), refutes these data, proving that in primates close to us such cells will not be rejected by the immune system.
Induced pluripotent stem cells are cells that are genetically reprogrammed into a state close to embryonic stem cells, which means that they can differentiate into almost any type of cell in the body. Induced stem cells, whose differentiation is directed towards certain cell types, are a renewable source of cells and tissues for the treatment of a variety of diseases, including Parkinson's disease, spinal cord injury, heart disease, diabetes and arthritis.
Induced pluripotent stem cells have great potential in the field of autologous transplantation using cells derived from the patient's own cells. However, the immunogenicity of iPSCs or their derivatives remains a matter of debate, and so far no direct comparison has been made between allogeneic and autologous transplants into the human or primate brain. In experiments on crab-eating macaques (Macaca fascicularis), Japanese scientists have shown that autologous transplantation of neurons obtained from IPSC causes only a minimal immune response in the brain. In contrast, allografts cause a pronounced immune response with activation of microglia and infiltration by leukocytes. Accordingly, more dopaminergic neurons survive in autografts. These results show the preference of autologous transplantation of nerve cells obtained from iPSCs in terms of minimizing the immune response from the brain. (Photo: Stem Cell Reports, Morizane et al.)Autologous transplantations of neurons derived from induced pluripotent stem cells performed on mice gave ambiguous results and did not allow us to come to a definite conclusion, since in some cases scientists observed rejection of transplanted cells, while in others they did not.
In addition, these studies did not reproduce the conditions of clinical use of neurons differentiated from IPSC. To study the consequences of autologous transplants on a biological species closer to humans, Japanese scientists reprogrammed the iPSCs of four monkeys into dopaminergic neurons that die in patients with Parkinson's disease. The introduction of these neurons into the brain of the same monkeys led to the development of only a minimal immune response. The transplanted cells themselves remained fully viable. The observation of the animals lasted about three months, during which no immunosuppressants were used.
In contrast, the introduction of such cells to immunologically incompatible recipients (allogeneic transplantation) caused the development of a stronger response from microglia and lymphocytes.
"These results provide grounds for starting autologous transplants – at least nerve cells – in a clinical setting," said the head of the study, Professor Jun Takahashi, MD, PhD, from the Center for iPS Cell Research and Application Kyoto University (Kyoto University). In addition, the transplantation of neurons to immunologically compatible recipients will avoid the appointment of immunosuppressants to patients and thereby prevent the development of undesirable side effects associated with suppression of immunity.
Portal "Eternal youth" http://vechnayamolodost.ru30.09.2013