FIELD: biotechnology.
SUBSTANCE: invention relates to biotechnology, namely to a method for bone marrow restitution. Method includes the following steps: (a) diagnosing hematopoietic stem cells (HSC) of bone marrow (BM) and peripheral blood (PB) leukocytes of a patient by genomic analysis or PCR diagnostics; (b) if the patient has clonal haematopoiesis, mobilization of HSC and HPC of the patient, on 5th and 6th day of mobilization – collection of autologous HSC and hematopoietic progenitor cells (HPC) by isolating leukoconcentrate of autologous mobilized mononuclear cells with maximum possible removal of pathological clone/clones HSC and HPC from BM and PB of the patient, purification of leucoconcentrate from erythrocytes, thrombocytes and granulocytes to obtain purified leucoconcentrate and its subsequent cryopreservation; (c) if the patient has clonal haemopoiesis and after step (b) – determining the patient's immune status and depending on the quantitative indicators of the status – non-myeloablative immunosuppression, or immunostimulation, or immunomodulation of the patient's body; (d) defrosting the leuconcentrate obtained at step (b), irradiating it with ionizing radiation in dose of 0.3–1.5 Gy for micro-damaging the genome of the HSC and HPC clones, genomic modulation and commissioning of HSC and HPC by incubation for 45–60 minutes of patient's leucoconcentrate containing HSC with DNA micro-damages, with a preparation of nucleosomal monomers of human genomic DNA to obtain a preparation for reinfusion thereof to a patient; (e) after step (c) and normalizing the patient’s blood, intravenous reinfusion of the preparation prepared at step (d); (f) immunotherapy of patient with antithymocyte globulin; (g) on 3rd, 6th, 9th and 12th months after stage (e) – diagnostics within the scope of stage (a) for monitoring of change of clonality of haematopoiesis.
EFFECT: invention provides recovery of polyclonality of haematopoiesis bynatural-like genome change of the dominant clone of autologous HSC and HPC.
3 cl, 16 dwg, 15 tbl, 4 ex
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Authors
Dates
2024-04-22—Published
2023-11-01—Filed