The human hematopoietic stem and progenitor cells in the complex therapy of the psychiatric disorders.
Prof. Andrey S. Bryukhovetskiy
For the first time the clinical administration of the hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the therapy of the psychiatric diseases has been mentioned in an academic literature in 2010 when the research of professor Vladimir Smirnov who headed the Research Institute of Experimental Cardiology of the FGBU Cardiology Research Center has been published. The team of Prof. Smirnov used the HSCs and HPCs of the umbilical blood in the therapy of the patients with schizophrenia and psychoorganic syndrome. In some of the psychiatric patients the therapy appeared quite effective for the correction of the intellectual-memory and emotional-volitional disorders. The method of therapy has been patented by the commercial structure known as Cryocenter (Patent RU 2413524). The researchers demonstrated effectiveness of the approach in the restoration of neurocognitive deficit in 10 cases of schizophrenia and in the correction of the cerebral-asthenic syndrome. Cognitive effects achieved after the administration of the cell concentration from umbilical blood to the patients in hypochondriac remission were represented in the pronounced metabolic (nootropic) and psychostimulating effects that manifested by activated intellectual activity, quicker thinking, corrected memory functions and increased the level of alertness. The effectiveness of the presented method is characterized both by stability and continuance.
This research has been accepted with skepticism and negativism by the scientific community, as the authors ignored the standard stages of pre-clinical research in animals and phase I-II to evaluate the safety of the proposed method. However, the researchers explained the absence of pre-clinical stage by the impossibility to model psychopathological disorders in animals and the safety of the administered material by its low immunogenicity and reactivity. The authors did not provide the explanations for the mechanisms of the detected clinical effectiveness of the umbilical blood HSCs and HPCs in the therapy of the psychiatric diseases. Possibly, it was not the objective of the research, or maybe the authors have no understanding of the mechanisms of the correction of the psychiatric disorders with the samples of the umbilical cord blood.
Further, the Russian scientific literature presented just separate non-systemized reports on the administration of the multiple transfusions of HSCs and HPCs of umbilical blood to treat the psychopathological disorders in humans and these reports do not deserve special attention. The experience of administering other allogeneic HSCs to treat the organic damages of the brain accompanied by the intellectual, memory and emotional-volitional disorders is described in the series of the foreign research.
The effectiveness of the clinical administration of the HSCs and HPCs of umbilical cord blood in the cases of organic damage of the brain cannot be questioned; and the correction of the psychiatric disorders in these cases is associated with the launch of the neuroregeneration and neuroreparation processes in the injured brain. To date, it has been shown that the regeneration in the neural tissue can be activated by the stem cells, and the mechanism is well studied and clear. Regeneration of the damaged neural tissue is provided by the fusion of the stem and progenitor cells of umbilical cord blood with the damaged cells if the brain, by the development of new intercellular contacts synapses and interactions between the main elements of the neural tissue. Another mechanism of the effect of the umbilical HSCs and HPCs on the injured neurons is explained by the bystander effect, when the influence of immature cell systems is conditioned by the regulatory and neurotrophic effect of the cytokins and neurotrophins expressed by the cell systems on the damaged tissues.
However, use of the stem and progenitor cells of the umbilical cord blood has one major drawback that crosses out all advantages. The therapy of the psychopathological disorders with the stem and progenitor cells requires the materials from two or three donors of the umbilical cord blood for every administration. The therapy implies 5 to 6 administrations per a course. Generally, the therapy demands 12 to 18 samples of umbilical blood donors of HSCs and HPCs. Apart from the chimerization of the patient’s organism, which is not taken into account by the researchers for some reason, it becomes obvious that the researcher is not able to repeat the achieved result because it is not possible to repeat the combinations of the donor HSCs and HPCs. This fact has always been a drawback in using the umbilical blood cells and fetal cell material. This is one of the main reasons why we have refused from using the fetal cell material and umbilical cord blood. If the researcher is not able to repeat his/her results, the value of this research is negligible.
The situation is different when autologous or haploidentical allogeneic biomaterial is used or the blood group, rhesus, immunophenotype and molecular-biological characteristics of the allogeneic mobilized HSCs and HPCs have been matched. When the clinical effect is received, it can be stabilized and when it is absent, the donor can be changed. This promises the opportunities to repeat the acquired results by other researchers following the available descriptions and makes it possible to use the available evidence of the genome and post-genome research to find the matching biomaterial.
For a decade we have been using the samples of allogeneic biomaterial based on the autologous and allogeneic HSCs and HPCs isolated from the patient or adult healthy donors and registered improvement and reduced psychopathological disorders as the consequence. The mechanism of cell adhesion of the administered HSCs and HPCs to the pia mater, development of the microconglomerates and new pia around them and further targeted migration of these cell systems to the site of injuries in the brain seem the main instrument of the restoration of ordered psychic activity in this kind of patients. In details these mechanisms have been described in the book Cell Transplantation and Tissue Engineering in the Therapy of Neural Diseases of the Humans in 2003. The microphotographs of this complex intracerebral process that we modeled in the brains of the experimental animals demonstrate unique ability of the cells to migrate inside the neural tissue following the concentration gradients of inflammation.
The effectiveness of corrections of the psychopathological disorders with HSCs and HPCs is associated with the restoration of the impaired informational-commutational links of various departments of the brain cortex in the CSF space between the membranes of the brain. This therapy is especially effective (over 52.3%) in the patients with developing organic defects after the abuse of neuroleptics, psychotropic or narcotic substances.