Mononuclear cells from human umbilical cord/placental blood: Assessment of allergenicity and impact on immune status in experimental warm-blooded animals
Year: 2024
Type: article
Abstract: Human mononuclear cells from umbilical cord blood (HUCBMCs) are used as the main or adjuvant therapy for treatment of about 80 different diseases, due to high proliferative activity of these cells, low immunogenicity and an opportunity of selecting rare HLA types for transplants. In this regard, assessment of cellular material in protocols of immunopharmacology is relevant. Our objective was to study allergenic and immunotoxic effects of mononuclear cells from human umbilical cord/placental blood as preclinical testing in laboratory animals. The study of type I hypersensitivity to HUCBMCs was carried out using a standard method for assessing bronchiolar spasm in male and female guinea pigs. The samples of tracheal sections were incubated in Ringer–Tyrode solution at the 2.5 per cent concentration of mononuclear cell suspension, with histamine hydrochloride serving a positive control. Antibody detection to HUCBMCs was carried out in the CBAxC57B2/6 male mice using by means of complement fixation test (indexed as absence of hemolysis of sheep erythrocytes). The mice were subjected to single intravenous injections of cell material exceeding the human therapeutic dose 10, 50 and 100-times (8.57 × 107 cells/kg, 4.28 × 108 cells/kg, 8.57 × 108 cells/kg body weight, respectively). Blood for analysis was taken 21 days after administration of the biomaterial. Blood serum from mice immunized with S. aureus was used as a positive control. A study of the phagocytic activity of neutrophils was carried out in male and female Wistar rats, which were subjected to a single intravenous injection of HUCBMCs at 10-fold therapeutic dosage. After 30 days, the phagocytic index and phagocytic number were studied using the ink test method, by analyzing 600 cells for each group. The median, upper and lower quartiles (Me (Q0.25-Q0.75)) were calculated; the hypotheses were compared using the Mann–Whitney U test. We didn’t detect anaphylactogenic activity and production of antibodies to cellular material after administration of HUCBMCs to the animals. In female rats, the phagocytic activity of neutrophils increased statistically significantly (p = 0.004) relative to control animals [56.5 (53.8-60.8) versus 44.0 (40.5-47.5), respectively]. In male rats, there was a tendency to increased phagocytic activity by 13% (p = 0.054). The phagocytic index in all compared groups remained within deviations of standard values (1.8-2.0). Human umbilical cord blood mononuclear cells do not exhibit an anaphylactogenic, and do not show any immunotoxic effect at 100-fold at the human therapeutic dosage (8.57 × 108 cells/kg). However, they contribute to increase of phagocytic activity of neutrophils, thus requiring further preclinical and clinical trials of efficiency and safety for usage of this biomaterial with high therapeutic potential.
Source: Medical Immunology (Russia)
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4408305025