Mononuclear cells of human umbilical cord-placental blood: assessment of allergenicity and impact on immune status in experiments on warm-blooded animals

Autor: Sergey V. Skupnevskii, Rodion V. Saveljev, Elena G. Pukhaeva, Yana V, Morozova, Sergey M. Radaev, Vladimir A. Smirnov, Andrey A. Grin
Jazyk: ruština
Rok vydání: 2019
Předmět:
Zdroj: Медицинская иммунология, Vol 0, Iss 0 (2019)
Druh dokumentu: article
ISSN: 1563-0625
2313-741X
DOI: 10.15789/1563-0625-MCO-3037
Popis: Human umbilical cord blood mononuclear cells (HUCBMCs) are used as the common or adjuvant therapy to treat about 80 different diseases. This is determined by high proliferative activity of cells, low immunogenicity and the possibility of selecting rare HLA types for transplants. In this regard, assessing the cellular material in protocols of immunopharmacology is relevant. Objective: to study the allergenic and immunotoxic effects of mononuclear cells of human umbilical cord-placental blood in the preclinical testing on animals. Materials and methods: 1. The study of type I hypersensitivity to HUCBMCs was carried out using a standard method for assessing bronchospasm in the trachea of male and female guinea pigs. Samples of tracheal sections were incubated in Ringer-Tyrode solution with concentration of mononuclear cell suspension 2.5 %, positive control – histamine hydrochloride. 2. Antibody detection to HUCBMCs was carried out on male mice of the CBAxC57B2/6 line using the complement fixation test (indication – absence of hemolysis of sheep erythrocytes). Mice were administrated single intravenous injection of cell material at 10, 50 and 100-fold the therapeutic dosage for humans (8.57∙107, 4.28∙108, 8.57∙108 cells/kg body weight (b.w.), respectively); blood for analysis was taken 21 days after the administration of the biomaterial. Positive control – serum from mice immunized with St. aureus. 3. A study of the phagocytic activity of neutrophils was carried out on male and female Wistar rats, which were administered 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 and analyzing 600 cells for each group. The median, upper and lower quartiles (Me (C25-C75)) were calculated; hypotheses were compared using the Mann-Whitney U test. Results: we didn't detect anaphylactogenic activity and production of antibodies to cellular material after administration of HUCBMCs to 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) and 44.0 (40.5-47.5), respectively); in male rats there was a tendency to increase phagocytic activity by 13 % (p = 0.054). The phagocytic index in all compared groups remained in the zone of fluctuations of standard values of 1.8 – 2.0. Conclusion: Human umbilical cord blood mononuclear cells do not have an anaphylactogenic, and at 100-fold at the therapeutic dosage (8.57∙108 cells/kg) an immunotoxic effect, but contribute to increase of phagocytic activity of neutrophils, which requires further preclinical and clinical trials of the effectiveness and safety of the use of biomaterial with high therapeutic potential.
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