Elimination of PKH26-labeled MMSC after allogeneic transplantation


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Abstract

The transplanted allogeneic multipotent mesenchymal stromal cells (MMSC) were previously thought to be poorly recognized by host immune system; the prolonged survival of these cells in host tissues was explained by their privileged immune status. As long as this concept is currently being revised, the understanding of MMSC routes should be reconsidered given the emerging role of host immune system in their gradual elimination. The study was focused upon elimination of PKH26-labeled MMSC, derived from umbilical cord, analyzed in animal models for two distinct pathologies: subtotal liver resection and critical skeletal muscle ischemia. Specific patterns of PKH26-positive macrophages (defined as CD68+ cells) were described for intact spleen and regenerating liver, and for the ischemic skeletal muscle, respectively. The PKH26-positive cells were observed in spleen of the subtotally hepatectomized model animals at 24 h. after surgery combined with MMSC transplantation; 83,2±4,6% of these were CD68+; the ratio reached 100% 3 days after transplantation. The PKH26-positive cells were also detected in regenerating liver starting from 3 days after transplantation, the great majority of them were CD68+ (96,8±2,2% and 96,3±2,6% for 3 and 10 days after transplantation, respectively). A different sort of host environment was provided by the damaged skeletal muscle model: productive phase of aseptic inflammation triggered by ischemia. The PKH26-positive fraction in the pool of macrophages significantly increased from 48,1 ±3,2% 3 days to 76,2±3,9% 30 days after transplantation. Thus, transplanted allogeneic MMSC are recognized and eliminated by host immune system. The rates of elimination depend on site of injection and time elapsed since the injection; the efficacy may reach 100%. The presence of РКН26 vital label (as well as any other exogenous label) in living cell can by no means solely prove its exogenous origin. The massive elimination of MMSC by host macrophages leads to impregnation of the latter with the dye that is masking the true presence of the former. The study accentuates the need of additional criteria for correct data interpretation.

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About the authors

IV. V Arutyunyan

Research Center for Obstetrics, Gynecology and Perinatology; Research Institute of Human Morphology of the RAMS

A. V Elchaninov

Research Center for Obstetrics, Gynecology and Perinatology; Research Institute of Human Morphology of the RAMS; Pirogov Russian National Research Medical University

T. H Fatkhudinov

Research Center for Obstetrics, Gynecology and Perinatology; Research Institute of Human Morphology of the RAMS; Pirogov Russian National Research Medical University

A. V Makarov

Research Center for Obstetrics, Gynecology and Perinatology; Research Institute of Human Morphology of the RAMS; Pirogov Russian National Research Medical University

E. Y Kananykhina

Research Center for Obstetrics, Gynecology and Perinatology; Research Institute of Human Morphology of the RAMS

G. B Bolshakova

Research Institute of Human Morphology of the RAMS

V. V Glinkina

Pirogov Russian National Research Medical University

D. V Goldshtein

Research Centre of Medical Genetics of the RAMS

G. T Sukhikh

Research Center for Obstetrics, Gynecology and Perinatology

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