Unmanipulated hematopoietic personalised therapy in the complex therapy of organic damage of the brain

First, the clinical use of hematopoietic personalised therapy and hematopoietic progenitor cells (HPCs) to treat cognitive disorders was mentioned in the work of the research team headed by Prof. Smirnov VN, from the Research Institute of the Experimental Cardiology of the State Cardiological Research Center in 2010. The cells and HPCs of umbilical cord blood were used in the therapy of the patients with schizophrenia and psychoorganic syndrome. They demonstrated quite high efficiency of the HPCs therapy in the correction of the cognitive and emotional disorders in the psychiatric patients. This method of treatment was patented in Russia by the commercial structure Cryocenter (Patent RU 2413524). The authors demonstrated effective restoration of neurocognitive deficit in 10 cases of schizophrenia and corrected cerebro-asthenic syndrome in the patients with imbecility. The cognitive effects of the umbilical cord blood cells administered according to the author’s method consist of the pronounced metabolic (nootropic) and psychostimulating effect in the patients in the state of hypochondriac remission, which manifests in the activated intellectual activity, improved thinking ability, memory and improved wakefulness. The efficiency of the method in the improvement of cognition is both stable and prolonged.

This research met skepticism and criticism in the medical community as the authors had ignored the standard stage of the pre-clinical trials in animal models and their ideas had been scaled up without the stage of evaluation of the safety of the proposed therapy (Phase I-II). However, the absence preclinical stage is explained by the absence of the model of psychopathological conditions in animals and the safety is conditioned by low reactivity an immunogenicity of the umbilical cord material. The authors do not give any explanations of the reasons and mechanisms of the clinical efficiency of the umbilical cord blood cells and HPCs in the therapy of mental disorders. Possibly, this was not the goal of the research, or, the authors have no understanding of the mechanisms of correction of the mental disorders by the samples of umbilical cord blood. Further, national academic literature published separate non-systematized research of multiple administrations of cells and HPCs of umbilical cord blood to treat mental diseases, but they hardly deserve discussion. The international research teams have published the evidence of using allogenic cells to treat organic damages of the brain that are accompanied by cognitive and emotional-volitional disorders.

The effectiveness of the clinical use of the cells and HPCs of umbilical cord blood in the therapy of the organic damage of the brain causes no doubts and correction of mental disorders in these cases seems to be associated with the triggered neuroregeneration and neuroreparation in the damaged brain. To date, it has been shown that regeneration of the neural tissue can be activated by using autologous cells and the mechanism of their work is well studied and clear. Regeneration of the damage neural tissue is provided by the fusion of the personalised therapy with the damaged cells of the brain by forming new interpersonalised contacts and restoration of inter-personalised relations and contacts between the main elements of neural tissue. The mechanism of action of the umbilical cells and HPCs can be also explained by the bystander effect, when the effect of the immature cell systems is conditioned by the regulatory and neurotrophic action on the damaged tissues of the cytokines and neurotrophins expressed by these cell systems.

However, the use umbilical cord blood cells has a drawback that crosses out all their benefits. Therapy of mental disorders requires 2-3 donors of umbilical cord blood per one administration. One course of the therapy consists of 5 to 6 administrations. That is, the therapy engages 12 to 18 samples of cells and HPCs of different donors of umbilical cord blood. Apart from the chimerization of the patient’s organisms, which is for some reason is never taken into account, it is obvious that any “wonderful” effect from the administration cannot be repeated, as you cannot repeat the combination of these donor compositions. It has always been one of the most important disadvantages of using umbilical cord materials and fetal cells. And if you are not able to repeat your results, the value of this research is null.

Use of the autologous and haploidentical allogenic biomaterial or the material prepared from the mobilized cells and HPCs of healthy donor who is immunocompatible by blood group, rhesus, immunophenotype and molecular-biological properties of bone marrow biomaterial. When you observe a clinical effect, you are always able to enhance it; in case no effect is observed, you can change the donor. Thus, the achieved results can be repeated by other researchers and doctors following the definitive characteristics of biomaterial and can engage the achievements of contemporary genome and post-genome studies to the selection of the necessary sample of bone-marrow biomaterial.
For a decade we have been using the samples of the allogenic biomaterial from healthy adult donors and observe clinical improvement and reduction of the psychopathological disorders in the patients with psychoorganic syndromes of various genesis. It seems that the main mechanism of the restoration of ordered mental activity is the mechanism of cell adhesion of the administered cells and HPCs on a pia mater, development of a new pia around the personalised microconglomerates and further targeted migration of these сell systems to the site of injury in the brain.

We described this mechanism in detail in our book Cell transplantation and tissue engineering in the therapy of neural disease of the humans in 2003. The photographs of this complicated intracerebral process that we modelled in the brain of the animal models are shown in the book to demonstrate the unique potential of the cells to migrate inside the neural tissue following the inflammation concentration gradient.

The effectiveness of correction of mental disorders by cells and HPCs is associated with the restoration of the information-commutation connections between various sections of the brain cortex in the CSF space between the membranes of the brain. This therapy is especially effective in the patients with developing organic defect induced by long administration of neuroleptics, narcotic drugs and psychotropic substances.