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. 2019 Jul 1;2(3):169-177.
doi: 10.1002/ame2.12073. eCollection 2019 Sep.

Cell therapy stimulates bone neoformation in calvaria defects in rats subjected to local irradiation

Ana Luisa Riul Sório  1 , Paula Katherine Vargas-Sanchez  1 , Roger Rodrigo Fernandes  1 , Dimitrius Leonardo Pitol  1 , Luiz Gustavo de Sousa  1 , Adriano Luiz Balthazar Bianchini  2 , Geraldo Batista de Melo  3 , Selma Siessere  1 , Karina Fittipaldi Bombonato-Prado  1
Affiliations

Cell therapy stimulates bone neoformation in calvaria defects in rats subjected to local irradiation

Ana Luisa Riul Sório et al. Animal Model Exp Med. .

Abstract

Background: The purpose of the study was to analyze the effect of cell therapy on the repair process in calvaria defects in rats subjected to irradiation.

Methods: Bone marrow mesenchymal cells were characterized for osteoblastic phenotype. Calvariae of male Wistar rats were irradiated (20 Gy) and, after 4 weeks, osteoblastic cells were placed in surgically created defects in irradiated (IRC) and control animals (CC), paired with untreated irradiated (IR) and control (C) animals. After 30 days, histological and microtomographic evaluation was performed to establish significant (P < 0.05) differences among the groups.

Results: Higher alkaline phosphatase detection and activity, along with an increase in mineralized nodules, in the IRC, C and CC groups compared to the IR group, confirmed an osteoblastic phenotype. Histology showed impaired bone neoformation following irradiation, affecting bone marrow composition. Cell therapy in the IRC group improved bone neoformation compared to the IR group. Microtomography revealed increased bone volume, bone surface and trabecular number in IRC group compared to the IR group.

Conclusion: Cell therapy may improve bone neoformation in defects created after irradiation.

Keywords: calvaria; cell therapy; irradiation; osteoblasts; rats.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
A, Alkaline phosphatase (ALP) activity of bone marrow mesenchymal cells cultured in basal growth medium (MEM) and osteogenic medium (MTS) after 10 d of culture. B, In situ ALP detection in bone marrow mesenchymal cells cultured in basal growth medium (MEM) and osteogenic medium (MTS) after 10 d of culture. C, Detection of mineralization nodules in bone marrow mesenchymal cells cultured in basal growth medium (MEM) and osteogenic medium (MTS) after 21 d of culture. *Significant difference at P < 0.05; Mann‐Whitney test
Figure 2
Figure 2
Histological sections of calvaria defect sites. A, Control group shows defect borders with lamellar bone (lb) and connective tissue (ct). B, Control group + cell therapy (CC) shows lamellar bone (BT) with organized connective tissue (ct). C, Irradiated group (IR) shows lamellar bone with osteoclast layer adjacent to Howship lacunae (thin arrow), disorganized connective tissue (ct) and granulation tissue (gt). D, Irradiated group + cell therapy (IRC) shows lamellar bone (lb) and woven bone (wb) with a osteoblast layer (thick arrow), blood vessels (bv) and connective tissue (CT). Hematoxylin and eosin stain. Scale bar = 200 μm
Figure 3
Figure 3
Histological sections of calvaria defect sites. A, Control group (C). B, Control group + cell therapy (CC) showing bone tissue (BT) and bone marrow (bm). C, Irradiated group (IR) showing adipocytic bone marrow (ad). D, Irradiated + cell therapy (IRC). Hematoxylin and eosin stain. Scale bar = 500 μm
Figure 4
Figure 4
Microtomographic 3D reconstruction images from calvaria defects of experimental groups. A, Control (C). B, Control + cell therapy (CC); C, Irradiated (IR). D, Irradiated + cell therapy (IRC)
Figure 5
Figure 5
Bone volume, bone surface, trabecular separation/thickness/number, connectivity density, open porosity and total porosity microtomographic quantitative parameters evaluated in control (C), control + cell therapy (CC), irradiated (IR) and irradiated + cell therapy (IRC) groups. Letters above error bars indicate statistically significant differences (P < 0.05; one‐way ANOVA)
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