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Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells.
Stem Cells Dev. 2008 Aug; 17(4):681-93.SC

Abstract

Adipose tissue-derived mesenchymal stem cells (AD-MSCs), which can differentiate into several lineages, have immunomodulatory properties similar to those of bone marrow-derived MSCs. However, the specific mechanism by which the immunomodulatory effect of MSCs occurs is not clear. In this study, we isolated canine AD-MSCs (cAD-MSCs) and induced their development into adipocyte, osteocyte, and neuron-like cells. We then investigated their phenotype and cytokine expression to determine whether they were able to exert an immunomodulatory effect and what the underlying mechanisms of this effect were. cAD-MSCs expressed CD44, CD90, and MHC class I and were also partially positive for the expression of CD34; however, they did not express CD14 and CD45. In addition, they expressed the mRNA of transforming growth factor beta (TGF-beta), IL-6, IL-8, CCL2, CCL5, vascular endothelial growth factor, hepatocyte growth factor (HGF), tissue inhibitor metalloproteinase-1/2, and cyclooxygenase-2 but not that of IL-10. Further, leukocyte proliferation induced by mitogens was suppressed when they were cocultured with irradiated cAD-MSCs, as well as with culture supernatants of cAD-MSCs alone. Moreover, TNF-alpha production significantly decreased, whereas TGF-beta, IL-6, and interferon-gamma production significantly increased in cAD-MSCs that were cocultured with leukocytes. Finally, immonomodulatory factors of MSCs, such as TGF-beta, HGF, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in cAD-MSCs that were cocultured with leukocytes; however, the production of PGE2 and IDO showed different kinetics, and leukocyte proliferation was effectively restored by PGE2 and IDO inhibitors. Taken together, these results indicate that the immunomodulatory effects of cAD-MSCs are associated with soluble factors (TGF-beta, HGF, PGE2, and IDO). Therefore, it is suggested that cAD-MSCs have a potential therapeutic use in the treatment of immune-mediated disease.

Authors+Show Affiliations

Department of Microbiology, College of Veterinary Medicine and Adult Stem Cell Research Center, Seoul National University, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18717642

Citation

Kang, Jung Won, et al. "Soluble Factors-mediated Immunomodulatory Effects of Canine Adipose Tissue-derived Mesenchymal Stem Cells." Stem Cells and Development, vol. 17, no. 4, 2008, pp. 681-93.
Kang JW, Kang KS, Koo HC, et al. Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells. Stem Cells Dev. 2008;17(4):681-93.
Kang, J. W., Kang, K. S., Koo, H. C., Park, J. R., Choi, E. W., & Park, Y. H. (2008). Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells. Stem Cells and Development, 17(4), 681-93. https://doi.org/10.1089/scd.2007.0153
Kang JW, et al. Soluble Factors-mediated Immunomodulatory Effects of Canine Adipose Tissue-derived Mesenchymal Stem Cells. Stem Cells Dev. 2008;17(4):681-93. PubMed PMID: 18717642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soluble factors-mediated immunomodulatory effects of canine adipose tissue-derived mesenchymal stem cells. AU - Kang,Jung Won, AU - Kang,Kyung-Sun, AU - Koo,Hye Cheong, AU - Park,Jeong Ran, AU - Choi,Eun Wha, AU - Park,Yong Ho, PY - 2008/8/23/pubmed PY - 2008/11/5/medline PY - 2008/8/23/entrez SP - 681 EP - 93 JF - Stem cells and development JO - Stem Cells Dev. VL - 17 IS - 4 N2 - Adipose tissue-derived mesenchymal stem cells (AD-MSCs), which can differentiate into several lineages, have immunomodulatory properties similar to those of bone marrow-derived MSCs. However, the specific mechanism by which the immunomodulatory effect of MSCs occurs is not clear. In this study, we isolated canine AD-MSCs (cAD-MSCs) and induced their development into adipocyte, osteocyte, and neuron-like cells. We then investigated their phenotype and cytokine expression to determine whether they were able to exert an immunomodulatory effect and what the underlying mechanisms of this effect were. cAD-MSCs expressed CD44, CD90, and MHC class I and were also partially positive for the expression of CD34; however, they did not express CD14 and CD45. In addition, they expressed the mRNA of transforming growth factor beta (TGF-beta), IL-6, IL-8, CCL2, CCL5, vascular endothelial growth factor, hepatocyte growth factor (HGF), tissue inhibitor metalloproteinase-1/2, and cyclooxygenase-2 but not that of IL-10. Further, leukocyte proliferation induced by mitogens was suppressed when they were cocultured with irradiated cAD-MSCs, as well as with culture supernatants of cAD-MSCs alone. Moreover, TNF-alpha production significantly decreased, whereas TGF-beta, IL-6, and interferon-gamma production significantly increased in cAD-MSCs that were cocultured with leukocytes. Finally, immonomodulatory factors of MSCs, such as TGF-beta, HGF, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in cAD-MSCs that were cocultured with leukocytes; however, the production of PGE2 and IDO showed different kinetics, and leukocyte proliferation was effectively restored by PGE2 and IDO inhibitors. Taken together, these results indicate that the immunomodulatory effects of cAD-MSCs are associated with soluble factors (TGF-beta, HGF, PGE2, and IDO). Therefore, it is suggested that cAD-MSCs have a potential therapeutic use in the treatment of immune-mediated disease. SN - 1557-8534 UR - https://www.unboundmedicine.com/medline/citation/18717642/Soluble_factors_mediated_immunomodulatory_effects_of_canine_adipose_tissue_derived_mesenchymal_stem_cells_ L2 - https://www.liebertpub.com/doi/full/10.1089/scd.2007.0153?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -