Effects of Hypoxia on the Immunomodulatory Properties of Adipose Tissue-Derived Mesenchymal Stem cells
Open accessAbstract
Adipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower than under standard culture conditions and ASC used for therapy therefore encounter a change from normoxic to hypoxic conditions. The effect of hypoxia on the regenerative potential of ASC has been investigated in a number of studies. The effect of hypoxia on the immunomodulatory function of ASC, however, remains to be determined. In the present study the effect of hypoxic (1% oxygen) culture conditions on human ASC was examined. ASC showed no signs of toxicity under low oxygen levels and no major immunophenotypical changes were observed, apart from a down regulation of the marker CD105. Oxygen tension had no effect on the proliferation of ASC and colony forming unit efficiency remained the same under 1 and 20% oxygen. Under both oxygen levels ASC were capable of strong upregulation of the immunomodulatory molecules indoleamine 2,3-dioxygenase (IDO) and programed death ligand-1 upon stimulation with IFN-γ and TNF-α, and, in addition, IDO activity as measured by the accumulation of l-kynurenine was not affected under hypoxia. The ability of ASC to inhibit anti-CD3/CD28 stimulated CD4(+) and CD8(+) T cell proliferation was not hampered by hypoxia. The results of the present study demonstrate that the immunosuppressive capacity of ASC is maintained under hypoxic conditions. These findings are important for the therapeutic use of ASC and may be applied for the in vitro generation of ASC with improved functionality for therapeutic use.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some studies reported conflicting results showing negative or no effects on MSCs by hypoxia.
“Yet, some studies reported conflicting results showing negative or no effects on MSCs by hypoxia [34–36].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [35]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Correspondence - Tranexamic acid for traumatic brain injury
(2005) · London School of Economics and Political Science Theses Online (London School of Economics and Political Science) · doi:10.1016/s0140-6736 · Cited by 11,894 · see citing works
Human Adipose Tissue Is a Source of Multipotent Stem Cells
Zuk, P. A., Zhu, M., Ashjian, P. H., Ugarte, D. A. D., Huang, J. I., Mizuno, H., Alfonso, Z. C., Fraser, J. K., Benhaim, P., & Hedrick, M. H. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-02-0105 · Cited by 6,669 · see citing works
(1996) · Institutional Research Information System University of Turin (University of Turin) · doi:10.1111/j · Cited by 5,486 · see citing works
Blanc, K. L., Frassoni, F., Ball, L. M., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M. E., Remberger, M., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60690-x · Cited by 2,692 · see citing works
Mesenchymal stem cells reside in virtually all post-natal organs and tissues
Meirelles, L. D. S., Chagastelles, P. C., & Nardi, N. B. (2006) · Journal of Cell Science · doi:10.1242/jcs.02932 · Cited by 2,472 · see citing works
Role for Interferon-γ in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells
Krampera, M., Cosmi, L., Angeli, R., Pasini, A., Liotta, F., Andreini, A., Santarlasci, V., Mazzinghi, B., Pizzolo, G., Vinante, F., et al. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0008 · Cited by 1,311 · see citing works
Strioga, M. M., Viswanathan, S., Darinskas, A., Slabý, O., & Michálek, J. (2012) · Stem Cells and Development · doi:10.1089/scd.2011.0722 · Cited by 826 · see citing works
Expanded Adipose-Derived Stem Cells for the Treatment of Complex Perianal Fistula
García‐Olmo, D., Herreros, D., Pascual, I., Pascual, J. A., Valle-Hernandez, E. D., Zorrilla, J., De-La-Quintana, P., García‐Arranz, M., & Pascual, M. (2009) · Diseases of the Colon & Rectum · doi:10.1007/dcr.0b013e3181973487 · Cited by 773 · see citing works
Rougier, P. R., Adenis, A., Ducreux, M. P., Forni, M. D., Bonneterre, J. M., Dembak, M., Clouet, P., Lebecq, A., Baille, P., Lefresne-Soulas, F., et al. (2000) · European Journal of Cancer · doi:10.1016/s0959-8049(00)00072-1 · Cited by 751 · see citing works
Duijvestein, M., Vos, A. C. W., Roelofs, H., Wildenberg, M. E., Wendrich, B. B., Verspaget, H. W., Kooy-Winkelaar, E. M. C., Koning, F., Zwaginga, J. J., Fidder, H. H., et al. (2010) · Gut · doi:10.1136/gut.2010.215152 · Cited by 622 · see citing works
Tsai, C., Chen, Y.-J., Yew, T., Chen, L., Wang, J., Chiu, C., & Hung, S. (2010) · Blood · doi:10.1182/blood-2010-05-287508 · Cited by 376 · see citing works
Reinders, M. E. J., de Fijter, J. W., Roelofs, H., et al. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0114 · Cited by 339 · see citing works
Sánchez-Elsner, T., Botella, L. M., Velasco, B., Langa, C., & Bernabéu, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207160200 · Cited by 326 · see citing works
Goossens, G. H., Bizzarri, A., Venteclef, N., Essers, Y., Cleutjens, J. P., Konings, E., Jocken, J. W. E., Čajlaković, M., Ribitsch, V., Clément, K., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.027813 · Cited by 324 · see citing works
Holzwarth, C., Vaegler, M., Gieseke, F., Pfister, S. M., Handgretinger, R., Kerst, G., & Müller, I. (2010) · BMC Cell Biology · doi:10.1186/1471-2121-11-11 · Cited by 314 · see citing works
Lee, H. C., An, S. G., Lee, H. W., Park, J.-S., Cha, K. S., Hong, T. J., Park, J. H., Lee, S. Y., Kim, S.-P., Kim, Y. D., et al. (2012) · Circulation Journal · doi:10.1253/circj.cj-11-1135 · Cited by 277 · see citing works
Fang, B., Song, Y., Liao, L., et al. (2007) · Transplantation Proceedings · doi:10.1016/j.transproceed.2007.08.103 · Cited by 238 · see citing works
McNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234 · see citing works
Crop, M. J., Baan, C. C., Korevaar, S. S., IJzermans, J. N. M., Pescatori, M., Stubbs, A., van IJcken, W. F. J., Dahlke, M. H., Eggenhofer, E., Weimar, W., et al. (2010) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2010.04256.x · Cited by 221 · see citing works
Self-citationHoogduijn, M. J., Crop, M. J., Peeters, A. M. A., van Osch, G. J. V. M., Balk, A. H. M. M., IJzermans, J. N. M., Weimar, W., & Baan, C. C. (2007) · Stem Cells and Development · doi:10.1089/scd.2006.0110 · Cited by 189 · see citing works
Self-citationLiu, L., Gao, J., Yuan, Y., Chang, Q., Liao, Y., & Lu, F. (2013) · Cell Biology International · doi:10.1002/cbin.10097 · Cited by 168 · see citing works
Nekanti, U., Dastidar, S., Venugopal, P., Totey, S. M., & Ta, M. (2010) · International Journal of Biological Sciences · doi:10.7150/ijbs.6.499 · Cited by 157 · see citing works
Valorani, M. G., Montelatici, E., Germani, A., Biddle, A., D’Alessandro, D., Strollo, R., Patrizi, M. P., Lazzari, L., Nye, E. L., Otto, W., et al. (2012) · Cell Proliferation · doi:10.1111/j.1365-2184.2012.00817.x · Cited by 154 · see citing works
Carrancio, S., López-Holgado, N., Sanchez-Guijo, F. M., Villarón, E. M., Barbado, M. V., Tabera, S., Díez‐Campelo, M., Blanco, J. F., Miguel, J. F. S., & del Cañizo, M. C. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2008.03.012 · Cited by 153 · see citing works
Fang, B., Song, Y. S., Zhao, R. C., Han, Q., & Lin, Q. (2007) · Transplantation Proceedings · doi:10.1016/j.transproceed.2007.02.091 · Cited by 96 · see citing works
Chung, D., Hayashi, K., Toupadakis, C. A., Wong, A., & Yellowley, C. E. (2010) · Research in Veterinary Science · doi:10.1016/j.rvsc.2010.10.012 · Cited by 70 · see citing works
Interaction between Adipose Tissue-Derived Mesenchymal Stem Cells and Regulatory T-Cells
Engela, A. U., Baan, C. C., Peeters, A. M. A., Weimar, W., & Hoogduijn, M. J. (2013) · Cell Transplantation · doi:10.3727/096368912x636984 · Cited by 69 · see citing works
Self-citationHealth-related quality of life of unrelated bone marrow donors in Japan
Nishimori, M., Yamada, Y., Hoshi, K., et al. (2002) · Blood · doi:10.1182/blood.v99.6.1995 · Cited by 67 · see citing works
Goossens, G. H., & Blaak, E. E. (2012) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328358fa87 · Cited by 62 · see citing works
Müller, J., Benz, K., Ahlers, M. J., Gaissmaier, C., & Mollenhauer, J. A. (2011) · Cell Transplantation · doi:10.3727/096368910x564094 · Cited by 59 · see citing works
Mesenchymal stem cells derived from adipose tissue are not affected by renal disease
Rhijn, M. R.-V., Reinders, M. E. J., de Klein, A., Douben, H., Korevaar, S. S., Mensah, F., Dor, F. J. M. F., IJzermans, J. N. M., Betjes, M. G. H., Baan, C. C., et al. (2012) · Kidney International · doi:10.1038/ki.2012.187 · Cited by 55 · see citing works
Self-citationWeijers, E. M., van den Broek, L. J., Waaijman, T., van Hinsbergh, V. W. M., Gibbs, S., & Koolwijk, P. (2011) · Tissue Engineering Part A · doi:10.1089/ten.tea.2010.0661 · Cited by 54 · see citing works
Donor-Derived Mesenchymal Stem Cells Remain Present and Functional in the Transplanted Human Heart
Hoogduijn, M. J., Crop, M. J., Peeters, A., Korevaar, S. S., Eijken, M., Drabbels, J. J. M., Roelen, D. L., Maat, A. P. W. M., Balk, A. H. M. M., Weimar, W., et al. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02450.x · Cited by 41 · see citing works
Self-citationEffect of hypoxia on equine mesenchymal stem cells derived from bone marrow and adipose tissue
Ranera, B., Remacha, A. R., Álvarez-Arguedas, S., Romero, A., Vázquez, F. J., Zaragoza, P., Martín‐Burriel, I., & Rodellar, C. (2012) · BMC Veterinary Research · doi:10.1186/1746-6148-8-142 · Cited by 41 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells
Antebi, B., Rodriguez, L. A., Walker, K. P., Asher, A. M., Kamucheka, R. M., Alvarado, L., Mohammadipoor, A., & Cancio, L. C. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-1007-x · Cited by 137 · see citing works
Han, K.-H., Kim, A.-K., Kim, M.-H., Kim, D.-H., Go, H.-N., Kang, D., Chang, J. W., Choi, S. W., Kang, K.-S., & Kim, D.-I. (2017) · Tissue and Cell · doi:10.1016/j.tice.2017.09.006 · Cited by 20 · see citing works
- Authors
- Roemeling-van Rhijn, M., Mensah, F. K. F., Korevaar, S. S., Leijs, M. J., van Osch, G. J. V. M., IJzermans, J. N. M., Betjes, M. G. H., Baan, C. C., Weimar, W., & Hoogduijn, M. J.
- Affiliations
- Erasmus MC (NL)
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 4
- Pages
- 203-203
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC3714546
- OpenAlex
- W1968353156
- Cited by
- 150
- References
- 34
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 9 · 2023: 15 · 2022: 28 · 2021: 15 · 2020: 5 · 2019: 10 · 2018: 11 · 2017: 16 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 4
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- adipose-derived stem cells, hypoxia, immunomodulation, indoleamine 2,3-dioxygenase, PD-L1, L-kynurenine, T cell proliferation inhibition, oxygen partial pressure, CD105, interferon-gamma, TNF-α, stem cell therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
