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Bone Marrow Mesenchymal Stem Cells Increase Survival after Ionizing Irradiation Combined with Wound Trauma: Characterization and Therapy - PubMed

Bone Marrow Mesenchymal Stem Cells Increase Survival after Ionizing Irradiation Combined with Wound Trauma: Characterization and Therapy

Juliann G Kiang et al. J Cell Sci Ther. 2014.

Abstract

The aim of this study was to investigate whether treatment with mesenchymal stem cells (MSCs) could improve survival after radiation combined injury. Bone marrow MSCs (BMSCs) were isolated from femurs of B6D2F1/J female mice and were expanded and cultivated in hypoxic conditions (5% O2, 10% CO2, 85% N2) over 30 days. BMSCs were transfused to mice 24 hr after combined injury due to 60Co-γ-photon irradiation (9.25 and 9.75 Gy, 0.4 Gy/min, bilateral) followed by skin wounding (CI). Water consumption, body weight, wound healing, and survival tallies were monitored during observation period. Mice subjected to CI experienced a dramatic moribundity over a 30-day observation period. Thus, CI (9.25 Gy)-animal group was characterized by 40% mortality rate while CI (9.75 Gy)-animal group had 100% mortality rate. CI-induced sickness was accompanied by body weight loss, increased water intake, and delayed wound healing. At the 30th day post-injury, bone marrow cell depletion still remained in surviving CI mice. Treatment of CI (9.25 Gy)-animal group with BMSCs led to an increase in 30-day survival rate by 30%, attenuated body weight loss, accelerated wound healing rate, and ameliorated bone-marrow cell depletion. Our novel results are the first to suggest that BMSC therapy is efficacious to sustain animal survival after CI.

Keywords: Body weight; Bone marrow; Radiation; Stem cell; Wound; Wound healing.

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Figures

Figure 1:
Figure 1:. Flow Cytometry Phenotype Analysis of mouse BMSCs - CD44+, Sca-1+, and CD34−

Immunofluorescence analysis of the expression of BMSC surface markers for phenotype cell assessment. BMSCs were obtained from bone marrow. They were cultivated for 45 days and subjected to 4 passages. (a-c) BMSCs expressed CD44 and Sca-1 but not CD34

Figure 2:
Figure 2:

Flow cytometric analysis and colony-forming unit of BMSCs. (A) Projections of Stro-1 (green) and Sca-1 (red). Counterstaining of nuclei is in blue (Heochst 33342). (B) Projections of Stro-1 (green), CD44 (blue), and mitochondrial GPD2 (red). (C) A representative colony of BMSCs.

Figure 3:
Figure 3:

BMSCs improved survival after whole-body ionizing irradiation combined with skin wound (CI). B6D2F1/J mice were exposed to γ-radiation followed by 15% TBSA skin-wound trauma. BMSCs (approximately 3 × 106 cells per mouse) were injected via tail vein 24 h after CI. N=10–11 per group and repeated once. (A) 9.25 Gy. 30% survival improvement was observed. *P<0.05 vs. CI +DMEM. (B) 9.75 Gy. 20% survival improvement was observed. *P<0.05 vs. CI+DMEM. CI: Radiation + Wound; DMEM: Dulbecco’s Modified Eagle’s Medium

Figure 4:
Figure 4:

BMSCs recovered body weights after whole-body ionizing irradiation combined with skin wound (CI). B6D2F1/J mice were exposed to γ-radiation followed by 15% TBSA skin-wound trauma. BMSCs (approximately 3 × 106 cells per mouse) were injected via tail vein 24 h after CI. N=10–11 per group and repeated once. a. 9.25 Gy. b. 9.75 Gy. *P<0.05 vs. respective body weights at day 0; **P<0.05 vs. respective body weight s at days 0, 1, 3, and 7; ^p<0.05 vs. CI+DMEM. CI: radiation + wound; DMEM: Dulbecco’s Modified Eagle’s Medium

Figure 5:
Figure 5:

BMSCs reduced water consumption after whole-body ionizing irradiation combined with skin wound (CI). B6D2F1/J mice were exposed to γ-radiation followed by 15% TBSA skin-wound trauma. BMSCs (approximately 3 × 106 cells per mouse) were injected via tail vein 24 h after CI. N=10–11 per group and repeated once. a. 9.25 Gy. b. 9.75 Gy. *p<0.05 vs. respective water consumption volumes at day 1; **p<0.05 vs. respective water consumption columns at days 1, 2, and 3; ^p<0.05 vs. CI+DMEM. CI: radiation + wound; DMEM: Dulbecco’s Modified Eagle’s Medium

Figure 6:
Figure 6:

BMSCs accelerated wound healing after whole-body ionizing irradiation combined with skin wound (CI). B6D2F1/J mice were exposed to γ-radiation followed by 15% TBSA skin-wound trauma. BMSCs (approximately 3 × 106 cells per mouse) were injected via tail vein 24 h after CI. N=10–11 per group, repeated once. a. 9.25 Gy. Wound was fully closed by day 21 after CI. *P<0.05 vs. CI+DMEM. b. 9.75 Gy. Wound was not fully healed by day 30 after CI. c. Representatives of wound closure on the back of mice. Mice were exposed to 9.25 Gy followed by 15% TBSA skin-wound trauma. BMSCs (approximately 3 × 106 cells per mouse) were injected via tail vein 24 h after CI. *p<0.05 vs. respective wound areas at day 1; ^p<0.05 vs. CI+DMEM. CI: radiation + wound; DMEM: Dulbecco’s Modified Eagle’s Medium

Figure 7:
Figure 7:

BMSCs increased bone marrow cellularity at day 30 after whole-body ionizing irradiation combined with skin wound (CI). a. Histology of bone marrow specimens (H&E staining). Hematopoietic cells are indicated with either yellow or black arrows. b and c. Relative counts of bone marrow cells. Experimental conditions: Mice were exposed to 9.25 Gy followed by 15% TBSA skin-wound trauma. BMSCs (approximately 3 × 106 cells per mouse) were injected via tail vein 24 h after CI. N=6 per group. CI: combined injury; DMEM: Dulbecco’s Modified Eagle’s Medium *P<0.05 vs. sham; ^p<0.05 vs. CI+DMEM. CI: radiation + wound; DMEM: Dulbecco’s Modified Eagle’s Medium

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References

    1. Iijima S (1982) Pathology of atomic bomb casualties. Acta Pathol Jpn 32 Suppl 2: 237–270. - PubMed
    1. Kishi HS (2000) Effects of the “special bomb”: recollections of a neurosurgeon in Hiroshima, August 8–15, 1945. Neurosurgery 47: 441–445. - PubMed
    1. Barabanova AV (2006) Significance of beta-radiation skin burns in Chernobyl patients for the theory and practice of radiopathology. Vojnosanit Pregl 63: 477–480. - PubMed
    1. Kiang JG, Jiao W, Cary LH, Mog SR, Elliott TB, et al. (2010) Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiat Res 173: 319–332. - PMC - PubMed
    1. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, et al. (2012) Wound trauma alters ionizing radiation dose assessment. Cell Biosci 2: 20. - PMC - PubMed

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