Выживаемость и устойчивость химеризма крови у мышей линии СВА послетрансплантации костного мозга от доноров различного происхождения, несущих ген EGFP

E. V. Bogdanenko; L. A. Sergievich; A. V. Karnaukhov; N. A. Karnaukhova; I. A. Lizunova

doi:10.25557/2310-0435.2021.04.30-40

E. V. Bogdanenko Institute of General Pathology and Pathophysiology, Moscow, Russian Federation http://orcid.org/0000-0002-3351-3916
L. A. Sergievich Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino of Moscow Region, Russian Federation http://orcid.org/0000-0001-7710-4703
A. V. Karnaukhov Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino of Moscow Region, Russian Federation http://orcid.org/0000-0003-3488-2067
N. A. Karnaukhova Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino of Moscow Region, Russian Federation http://orcid.org/0000-0002-8606-4739
I. A. Lizunova Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino of Moscow Region, Russian Federation

DOI: https://doi.org/10.25557/2310-0435.2021.04.30-40

Keywords: GVHD, bone marrow transplantation, mice, EGFP, fluorescence microscopy, allogeneic transplantation, full loss of chimerism

Abstract

Background. Allogeneic bone marrow transplantation (BMT) often causes a serious complication, graft-versus-host disease (GVHD), that reduces survival of recipients. Despite multiple studies, there is no complete understanding of what factor combination might minimize the phenomenon of GVHD.

The aim of the study was searching for the best combinations of donor-recipient pairs by sex and origin based on the survival and stability of blood chimerism using murine models of allogeneic and semi-allogeneic transplantation.

Materials and methods. The donors of bone marrow (BM) were mice carrying the GFP gene, which were derived from the C57Bl/6 strain, and reciprocal F1 hybrids ♀СВА × ♂C57BL/6 GFP⁺and ♀C57BL/6 GFP⁺× ♂♀СВА. The recipients were animals of inbred CBA (for allogeneic and semi-allogeneic BMT) and C57Bl/6 (for syngeneic BMT) strains. One day before BMT (1.5 × 10⁷ cells per mouse), all recipients were irradiated. BM was transplanted from females to males and females and from males only to males. A drop of recipients' blood was examined under a fluorescent microscope without fixation every week, starting from day 7 after transplantation.

Results. The longest survival after allogeneic and semi-allogeneic BMT was observed in female recipients with using females as donors (41 (22–330) days and 140,5 (107-218) days, respectively). Donor platelets and leukocytes were found in the blood of most of the recipients of all groups at 7 days after BMT; in some recipients, these cells could not be detected any more at 1-7 weeks after semi-allogeneic and allogeneic transplantation. In a number of cases, complete loss of the donor cells resulted in a significant increase in survival of recipients, especially in allogeneic transplantation.

Conclusions The donor♀-recipient♀ combination was the best and the donor♂–recipient♂ combination was the worst for survival of recipients, regardless of their degree of relationship with donors, in all cases of semi-allogeneic and allogeneic BMT. In syngeneic BMT, all donor-recipient combinations proved to be equally effective. Complete loss of chimerism may prolong rather than shorten the survival time of recipients.

Survival and stability of blood chimerism in CBA mice after bone marrow transplantation from donors of various origin carrying the EGFP gene

Abstract