Therapeutic effect of exogenous bone marrow‑derived mesenchymal stem cell transplantation on silicosis 
via paracrine mechanisms in rats

Zhao,Man‑Man; Cui,Jian‑Zhong; Cui,Ying; Li,Ran; Tian,Yan‑Xia; Song,Si‑Xin; Zhang,Juan; Gao,Jun‑Ling

doi:10.3892/mmr.2013.1580

September 2013 Volume 8 Issue 3

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September 2013 Volume 8 Issue 3

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Article

Therapeutic effect of exogenous bone marrow‑derived mesenchymal stem cell transplantation on silicosis via paracrine mechanisms in rats

Authors:
- Man‑Man Zhao
- Jian‑Zhong Cui
- Ying Cui
- Ran Li
- Yan‑Xia Tian
- Si‑Xin Song
- Juan Zhang
- Jun‑Ling Gao
View Affiliations / Copyright

Affiliations: School of Basic Medical Science, Hebei United University, Tangshan, Hebei 063000, P.R. China, Tangshan Workers' Hospital, Tangshan, Hebei 063000, P.R. China, Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Pages: 741-746
|
Published online on: July 10, 2013

https://doi.org/10.3892/mmr.2013.1580
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Abstract

Silicosis is a well‑known occupational disease, characterized by epithelial injury, fibroblast proliferation, expansion of the lung matrix and dyspnea. At present, no effective treatment methods for silicosis have been identified. The present study aimed to investigate the protective potential of exogenous bone marrow‑derived mesenchymal stem cell (BMSC) transplantation on experimental silica‑induced pulmonary fibrosis in rats and analyze the underlying paracrine mechanisms associated with its therapeutic effects. BMSCs were isolated, cultured and passaged from male Sprague‑Dawley (SD) rat bone marrow. Third‑generation BMSCs were identified by flow cytometry using FITC staining. Following the successful establishment of the silicosis model, exogenous BMSCs were infused into female adult SD rats via the tail vein. Lungs were evaluated using hematoxylin and eosin (H&E) staining. The expression of interleukin‑1 receptor antagonist (IL‑1RA), interleukin‑1 (IL‑1) and tumor necrosis factor α (TNF‑α) protein was detected by immunohistochemistry and western blot analysis. Co‑localization of sex determining region Y (SRY) and IL‑1RA expression was determined by double‑label immunofluorescence. The distribution of transplanted BMSCs was tracked by monitoring the expression of SRY in rats. Treatment with BMSCs was found to protect the lungs against injury and fibrosis by the suppression of upregulated IL‑1 and TNF‑α protein, via triggering IL‑1RA secretion. This mechanism was hypothesized to be mediated by paracrine signaling. These results indicate that the release of IL‑1RA from BMSCs via paracrine mechanisms significantly blocks the production and/or activity of IL‑1 and TNF‑α. The present study provides an experimental basis for cellular therapy in silicosis.

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1	Rimal B, Greenberg AK and Rom WN: Basic pathogenetic mechanisms in silicosis: current understanding. Curr Opin Pulm Med. 11:169–173. 2005. View Article : Google Scholar : PubMed/NCBI
2	Herzog EL, Chai L and Krause DS: Plasticity of marrow-derived stem cells. Blood. 102:3483–3493. 2003. View Article : Google Scholar : PubMed/NCBI
3	Nishida H, Nakayama M, Tanaka H, et al: Safety of autologous bone marrow stromal cell transplantation in dogs with acute spinal cord injury. Vet Surg. 41:437–442. 2012. View Article : Google Scholar : PubMed/NCBI
4	Osanai T, Kuroda S, Sugiyama T, et al: Therapeutic effects of intra-arterial delivery of bone marrow stromal cells in traumatic brain injury of rats - in vivo cell tracking study by near-infrared fluorescence imaging. Neurosurgery. 70:435–444. 2012. View Article : Google Scholar
5	Zhao L, Feng Z, Hu B, Chi X and Jiao S: Ex vivo-expanded bone marrow mesenchymal stem cells facilitate recovery from chemically induced acute liver damage. Hepatogastroenterology. 59:2389–2394. 2012.PubMed/NCBI
6	Islam MN, Das SR, Emin MT, et al: Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med. 18:759–765. 2012. View Article : Google Scholar : PubMed/NCBI
7	Luan Y, Zhang X, Kong F, Cheng GH, Qi TG and Zhang ZH: Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism. Int Immunopharmacol. 14:432–437. 2012. View Article : Google Scholar : PubMed/NCBI
8	Aslam M, Baveja R, Liang OD, et al: Bone marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am J Respir Crit Care Med. 180:1122–1130. 2009. View Article : Google Scholar : PubMed/NCBI
9	Ortiz LA, Gambelli F, McBride C, et al: Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA. 100:8407–8411. 2003. View Article : Google Scholar : PubMed/NCBI
10	Luan Y, Zhang ZH, Wei DE, et al: Implantation of mesenchymal stem cells improves right ventricular impairments caused by experimental pulmonary hypertension. Am J Med Sci. 343:402–406. 2012. View Article : Google Scholar : PubMed/NCBI
11	Rojas M, Xu J, Woods CR, et al: Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 33:145–152. 2005. View Article : Google Scholar : PubMed/NCBI
12	Nemeth K, Keane-Myers A, Brown JM, et al: Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma. Proc Natl Acad Sci USA. 107:5652–5657. 2010. View Article : Google Scholar : PubMed/NCBI
13	Wang PP, Xie DY, Liang XJ, et al: HGF and direct mesenchymal stem cells contact synergize to inhibit hepatic stellate cells activation through TLR4/NF-kB pathway. PLoS One. 7:e434082012. View Article : Google Scholar : PubMed/NCBI
14	Jin P, Zhang X, Wu Y, et al: Streptozotocin-induced diabetic rat-derived bone marrow mesenchymal stem cells have impaired abilities in proliferation, paracrine, antiapoptosis, and myogenic differentiation. Transplant Proc. 42:2745–2752. 2010. View Article : Google Scholar
15	Xu M, Uemura R, Dai Y, Wang Y, Pasha Z and Ashraf M: In vitro and in vivo effects of bone marrow stem cells on cardiac structure and function. J Mol Cell Cardiol. 42:441–448. 2007. View Article : Google Scholar : PubMed/NCBI
16	Mezey E: The therapeutic potential of bone marrow-derived stromal cells. J Cell Biochem. 112:2683–2687. 2011. View Article : Google Scholar : PubMed/NCBI
17	Reis LA, Borges FT, Simões MJ, Borges AA, Sinigaglia-Coimbra R and Schor N: Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats. PLoS One. 7:e440922012. View Article : Google Scholar
18	Bakondi B, Shimada IS, Perry A, et al: CD133 identifies a human bone marrow stem/progenitor cell sub-population with a repertoire of secreted factors that protect against stroke. Mol Ther. 17:1938–1947. 2009. View Article : Google Scholar : PubMed/NCBI
19	Burdon TJ, Paul A, Noiseux N, Prakash S and Shum-Tim D: Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential. Bone Marrow Res. 2011:Dec 6–2010.(Epub ahead of print).
20	Arend WP: Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest. 88:1445–1451. 1991. View Article : Google Scholar : PubMed/NCBI
21	Ortiz LA, Dutreil M, Fattman C, et al: Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci USA. 104:11002–11007. 2007. View Article : Google Scholar : PubMed/NCBI
22	Smajilagić A, Aljičević M, Redžić A, Filipović S and Lagumdžija A: Rat bone marrow stem cells isolation and culture as a bone formative experimental system. Bosn J Basic Med Sci. 13:27–30. 2013.PubMed/NCBI
23	Abkowitz JL, Robinson AE, Kale S, Long MW and Chen J: Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood. 102:1249–1253. 2003. View Article : Google Scholar : PubMed/NCBI
24	Kinnaird T, Stabile E, Burnett MS, et al: Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 109:1543–1549. 2004. View Article : Google Scholar : PubMed/NCBI
25	Nagaya N, Kangawa K, Itoh T, et al: Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 112:1128–1135. 2005. View Article : Google Scholar : PubMed/NCBI
26	Sharma RI and Snedeker JG: Paracrine interactions between mesenchymal stem cells affect substrate driven differentiation toward tendon and bone phenotypes. PLoS One. 7:e315042012. View Article : Google Scholar
27	Krasnodembskaya A, Song Y, Fang X, et al: Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 28:2229–2238. 2010. View Article : Google Scholar : PubMed/NCBI
28	Zhang K and Phan SH: Cytokines and pulmonary fibrosis. Biol Signals. 5:232–239. 1996. View Article : Google Scholar
29	Kolb M, Margetts PJ, Anthony DC, Pitossi F and Gauldie J: Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest. 107:1529–1536. 2001. View Article : Google Scholar : PubMed/NCBI
30	Zhang Y, Lee TC, Guillemin B, Yu MC and Rom WN: Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure. J Immunol. 150:4188–4196. 1993.PubMed/NCBI
31	Piguet PF, Vesin C, Grau GE and Thompson RC: Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica. Cytokine. 5:57–61. 1993. View Article : Google Scholar : PubMed/NCBI