The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury

Abstract

The aim of this study was to investigate the effects and mechanisms of mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone marrow cell apoptosis effects in irradiated mice, and to research the safe and effective dosage of MSCs in mice with total body irradiation (TBI). After BALB/c mice were irradiated with 5.5 Gy cobalt-60 gamma-rays, the following were observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F) counts of bone marrow cells and pathological changes in the medulla. The survival of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined. The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone marrow cells in the control group was higher at 24 h after radiation. A lower ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well as a greater number of haematopoietic islands and megalokaryocytes in the bone marrow, were observed in the MSC-treated groups. MSCs induced recovery of CFU-GM and CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 x 10(8) kg(-1) of MSCs increased mortality. These results indicate that MSCs protected and treated irradiated mice by inducing haematopoiesis and reducing apoptosis. MSCs may be a succedaneous or intensive method of haematopoietic stem cell transplantation under certain radiation dosages, and could provide a valuable strategy for acute radiation syndrome.

Figure 1

The sry gene of mesenchymal stem cells (MSCs) of mice was detected on day 30 after irradiation and MSC infusion. BM, bone marrow cells; P, positive control; N, negative control; M, DL-2000 marker; sry, 239 bp.

Figure 2

Effect of mesenchymal stem cells (MSCs) on the leukocyte count in sublethally irradiated mice. Each data point represents the mean ± standard deviation obtained from eight mice. Statistical significance was determined by comparison between the irradiated control group and the MSC group (p < 0.05) (every group, n _ 20). WBC, white blood cell.

Figure 3

Effect of mesenchymal stem cells (MSCs) on the haemoglobin (HGB) count in sublethally irradiated mice. Each data point represents the mean ± standard deviation obtained from eight mice. Statistical significance was determined by comparison between the irradiated control group and the MSC group on days 5, 6, 8, 13, 18 and 19 (p < 0.05).

Figure 4

Effect of mesenchymal stem cells (MSCs) on the platelet (PLT) count in sublethally irradiated mice. Each data point represents the mean ± standard deviation obtained from eight mice. Statistical significance was determined by comparison between the irradiated control group and the MSC group on days 20, 26 and 31 (p < 0.05), (every group, n _ 20).

Figure 5.The.

The pathological section of the sternum medulla in the (a) mesenchymal stem cell and (b) control groups (haematoxylin and eosin, ×200).The arrows indicate megacaryocytes (every group, n _ 5).

Figure 6

(a) Mean survival time and (b) survival curve for each group. The mean survival time was 8.55 ± 0.94 days in Group A (BALB/c mice treated with 1 × 10⁹ kg⁻¹ bone marrow cells (BMCs) after 8 Gy of total body irradiation (TBI)). The mean survival time in Group B (BALB/c mice treated with BMC+1.5 × 10⁸ kg⁻¹ MSCs after 8.0 Gy TBI) was 7 days. The mean survival time in Group C (BMCs+5 × 10⁷ kg⁻¹ MSCs) was 14.5 ± 1.65 days. The mean survival time in Group D (BMCs+2.5 × 10⁷ kg⁻¹ MSCs) was 15.1 ± 1.55 days. # indicates p < 0.05 when compared with group A (every group, n _ 20).