Volume 16 Supplement 3

Sepsis 2012

Open Access

Erythropoietin enhances the effects of transplanted mesenchymal stem cells in an experimental model of endotoxemia

  • A Sorokina1,
  • A Averyanov1,
  • F Zabozlaev1,
  • A Konoplyannikov2,
  • D Akulshin1 and
  • O Kuzovlev1
Critical Care201216(Suppl 3):P20


Published: 14 November 2012


Mesenchymal stem cells (MSCs) are able to reduce systemic inflammatory response in an experimental sepsis. One of the limiting factors of MSC therapy is a high degree of apoptosis of transplanted cells. On the basis of recently detected receptors for erythropoietin (EPO) on the surface of MSCs we hypothesized that introduction of EPO together with MSCs may increase survival of grafted MSCs and improve the clinical efficacy of cell transplantation.


Fifty Wistar male rats were randomized into five groups with 10 animals in each: Group 1 were healthy controls, Groups 2 to 5 were intraperitoneally introduced bacterial LPS 20 mg/kg. Two hours later LPS injection animals received the following intravenous treatment: 4 × 105 allogeneic MSCs (Group 3), 8.5 μg recombinant EPO-β (Group 4), MSCs and EPO in the same doses (Group 5). Surviving animals were euthanized on the fourth day. The morphological study, white blood cell count (WBC) and serum level of IL-1β, IL-2, IL-6, and TNFα measurement were performed.


The highest WBC was found in the group of combined treatment EPO + MSCs. The serum IL-1β level in Groups 2 and 4 was significantly higher than in healthy and treated with MSCs and EPO + MSCs animals. The main results of the morphologic analysis of different tissues in the groups are presented in Table 1. The most significant differences in the LPS + EPO group were found in the lymphoid tissue - considerable hyperplasia of spleen white pulp and thymus cortex (Figure 1).
Table 1

Morphometric characteristics of the examined tissues in the experimental groups







Alveolar septal thickening (μM)

10.32 ± 2.05

31.25 ± 2.9

15.3 ± 2.29*

28.6 ± 4.1

10.82 ± 1.08**

Kidney tubular dystrophy (point)


2.54 ± 0.31

2.22 ± 0.29

1.90 ± 0.12*

0.74 ± 0.19**

T-lymphocyte volume in thymus cortex (%)

86.24 ± 2.88

34.59 ± 1.34

49.37 ± 2.16

38.21 ± 1.73

81.48 ± 2.63**

Spleen white pulp volume (%)

23.95 ± 2.8

11.15 ± 3.8

19.9 ± 2.92

22.8 ± 0.98

27.15 ± 2.89*

*P < 0.05, **P < 0.01 compared with LPS group.

Figure 1

Representative hematoxylin and eosin staining of thymus tissue 96 hours post LPS injection (×100).


Combined treatment with EPO and MSCs can reduce acute lung injury and kidney damage, cause hyperplasia of lymphoid tissue and enhance the immune response more than separate treatment in an experimental model of endotoxemia in rats.

Authors’ Affiliations

Federal Research Clinical Center FMBA of Russia
Radiologic Research Center


© Sorokina et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.