Intrinsic Variability Present in Wharton’s Jelly Mesenchymal Stem Cells and T Cell Responses May Impact Cell Therapy
Open accessAbstract
Wharton’s jelly mesenchymal stem cells (WJ-MSC) exhibit immunomodulatory effects on T cell response. WJ-MSC are easy to collect, process, and proliferate rapidly in culture, but information on the variability of individual cell samples impacting upon in vitro expansion, immunomodulatory potential, and aging processes is still lacking. We propose to evaluate the immunomodulatory cytokine profile and capacity to inhibit T cell proliferation of WJ-MSC progressing to replicative senescence in order to analyze if expected responses are affected. Our results show that the gene expression of immunomodulatory molecules varied among samples with no specific pattern present. In coculture, all WJ-MSC were capable of inhibiting mitogen-activated CD3+ T cell proliferation, although to different degrees, and each PBMC responded with a different level of inhibition. Thus, we suggest that each WJ-MSC displays unique behavior, differing in patterns of cytokine mRNA expression and immunomodulatory capacity. We believe that variability between samples may play a role in the effectiveness of WJ-MSC employed therapeutically.
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MSC cell lines exhibit variety in functional properties such as immunomodulatory cytokine expression.
“MSC cell lines exhibit variety in functional properties such as immunomodulatory cytokine expression72”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [72]
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006) · Cytotherapy · doi:10.1080/14653240600855905 · Cited by 17,766 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Mesenchymal stem cells in health and disease
Uccelli, A., Moretta, L., & Pistoia, V. (2008) · Nature reviews. Immunology · doi:10.1038/nri2395 · Cited by 3,750 · see citing works
Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., & Gianni, A. M. (2002) · Blood · doi:10.1182/blood.v99.10.3838 · Cited by 3,226 · see citing works
Ren, G., Zhang, L., Zhao, X., Xu, G., Zhang, Y., Roberts, A. I., Zhao, R. C., & Shi, Y. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2007.11.014 · Cited by 2,101 · see citing works
Horwitz, E. M., Blanc, K. L., Dominici, M., Mueller, I., Slaper‐Cortenbach, I., Marini, F. C., Deans, R. J., Krause, D. S., & Keating, A. (2005) · Cytotherapy · doi:10.1080/14653240500319234 · Cited by 2,074 · see citing works
Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications
Bianco, P., Riminucci, M., Gronthos, S., & Robey, P. G. (2001) · Stem Cells · doi:10.1634/stemcells.19-3-180 · Cited by 1,944 · see citing works
Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues.
Friedenstein, A. J., Kv, P., KUROLESOVA, A. I., & Frolova, G. P. (1968) · PubMed · Cited by 1,921 · see citing works
Human mesenchymal stem cells modulate B-cell functions
Corcione, A., Benvenuto, F., Ferretti, E., Giunti, D., Cappiello, V., Cazzanti, F., Risso, M., Gualandi, F., Mancardi, G. L., Pistoia, V., et al. (2006) · Blood · doi:10.1182/blood-2005-07-2657 · Cited by 1,767 · see citing works
HETEROTOPIC TRANSPLANTS OF BONE MARROW
Friedenstein, A. J., Kv, P., KUROLESOVA, A. I., & Frolova, G. P. (1968) · Transplantation · doi:10.1097/00007890-196803000-00009 · Cited by 1,703 · see citing works
Meisel, R., Zibert, A., Laryea, M. D., Göbel, U., Däubener, W., & Dilloo, D. (2004) · Blood · doi:10.1182/blood-2003-11-3909 · Cited by 1,638 · see citing works
Krampera, M., Glennie, S. J., Dyson, J., Scott, D. M., Laylor, R. M., Simpson, E., & Dazzi, F. (2003) · Blood · doi:10.1182/blood-2002-07-2104 · Cited by 1,597 · see citing works
Tse, W. T., Pendleton, J. D., Beyer, W., Egalka, M. C., & Guinan, E. C. (2003) · Transplantation · doi:10.1097/01.tp.0000045055.63901.a9 · Cited by 1,501 · see citing works
Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications
Wang, Y., Chen, X., Cao, W., & Shi, Y. (2014) · Nature Immunology · doi:10.1038/ni.3002 · Cited by 1,452 · see citing works
Jiang, X.-X., Zhang, Y., Liu, B., Zhang, S.-X., Wu, Y., Yu, X.-D., & Mao, N. (2005) · Blood · doi:10.1182/blood-2004-02-0586 · Cited by 1,345 · 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
Waterman, R. S., Tomchuck, S. L., Henkle, S. L., & Betancourt, A. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010088 · Cited by 1,238 · see citing works
Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process
Wagner, W., Horn, P., Castoldi, M., Diehlmann, A., Bork, S., Saffrich, R., Beneš, V., Blake, J., Pfister, S. M., Eckstein, V., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002213 · Cited by 1,134 · see citing works
Spaggiari, G. M., Capobianco, A., Becchetti, S., Mingari, M. C., & Moretta, L. (2005) · Blood · doi:10.1182/blood-2005-07-2775 · Cited by 1,057 · see citing works
Aging of mesenchymal stem cell in vitro
Bonab, M. M., Alimoghaddam, K., Talebian, F., Ghaffari, S. H., Ghavamzadeh, A., & Nikbin, B. (2006) · BMC Cell Biology · doi:10.1186/1471-2121-7-14 · Cited by 888 · see citing works
Owen, M. E. (1988) · Journal of Cell Science · doi:10.1242/jcs.1988.supplement_10.5 · Cited by 829 · see citing works
Lazarus, H. M., Haynesworth, S. E., Gerson, S. L., Rosenthal, N. S., & Caplan, A. I. (1995) · PubMed · Cited by 749 · see citing works
English, K., Ryan, J. M., Tobin, L., Murphy, M. J., Barry, F., & Mahon, B. P. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.03874.x · Cited by 674 · see citing works
Ren, G., Zhao, X., Zhang, L., Zhang, J., L'Huillier, A., Ling, W., Roberts, A. I., Le, A. D., Shi, S., Shao, C., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902023 · Cited by 655 · see citing works
Secretion of immunoregulatory cytokines by mesenchymal stem cells
Kyurkchiev, D. S. (2014) · World Journal of Stem Cells · doi:10.4252/wjsc.v6.i5.552 · Cited by 619 · see citing works
Immune Properties of Human Umbilical Cord Wharton's Jelly-Derived Cells
Weiss, M. L., Anderson, C., Medicetty, S., Seshareddy, K., Weiss, R. J., VanderWerff, I., Troyer, D. L., & McIntosh, K. R. (2008) · Stem Cells · doi:10.1634/stemcells.2007-1028 · Cited by 613 · see citing works
IFN‐γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease
Polchert, D., Sobinsky, J., Douglas, G., Kidd, M. E., Moadsiri, A., Reina, E., Genrich, K., Mehrotra, S., Setty, S., Smith, B., et al. (2008) · European Journal of Immunology · doi:10.1002/eji.200738129 · Cited by 580 · see citing works
Cho, D. I., Kim, M. R., Jeong, H. Y., Jeong, H. C., Jeong, M. H., Yoon, S. H., Kim, Y. S., & Ahn, Y. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.135 · Cited by 543 · see citing works
Raffaghello, L., Bianchi, G., Bertolotto, M. B., Montecucco, F., Busca, A., Dallegri, F., Ottonello, L. C., & Pistoia, V. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0416 · Cited by 518 · see citing works
Turinetto, V., Vitale, E., & Giachino, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071164 · Cited by 484 · see citing works
Mesenchymal stem cells: a double-edged sword in regulating immune responses
Li, W., Ren, G., Huang, Y., Su, J., Han, Y., Li, J., Chen, X., Cao, K., Chen, Q., Shou, P., et al. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.26 · Cited by 434 · see citing works
Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues
Yoo, K. H., Jang, I. K., Lee, M. W., Kim, H. E., Yang, M. S., Eom, Y. W., Lee, J. E., Kim, Y. J., Yang, B. S. K., Jung, H. L., et al. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.06.010 · Cited by 417 · see citing works
Sheng, H., Wang, Y., Jin, Y., Zhang, Q., Zhang, Y., Wang, L., Shen, B., Yin, S., Liu, W., Cui, L., et al. (2008) · Cell Research · doi:10.1038/cr.2008.80 · Cited by 390 · see citing works
p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351 · see citing works
Neuß, S., Becher, E., Wöltje, M., Tietze, L., & Jahnen‐Dechent, W. (2004) · Stem Cells · doi:10.1634/stemcells.22-3-405 · Cited by 346 · see citing works
Characterization of bone marrow-derived mesenchymal stem cells in aging
Baker, N., Boyette, L. B., & Tuan, R. S. (2014) · Bone · doi:10.1016/j.bone.2014.10.014 · Cited by 281 · see citing works
Najar, M., Raicevic, G., Boufker, H. I., Fayyad‐Kazan, H., Bruyn, C. D., Meuleman, N., Bron, D., Toungouz, M., & Lagneaux, L. (2010) · Cellular Immunology · doi:10.1016/j.cellimm.2010.06.006 · Cited by 277 · see citing works
DelaRosa, O., Lombardo, E., Beraza, A., Mancheño‐Corvo, P., Ramirez, C., Menta, R., Rico, L., Camarillo‐Retamosa, E., García‐García, L., Abad, J. L., et al. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0630 · Cited by 271 · see citing works
Chang, C., Yen, M., Chen, Y., Chien, C., Huang, H., Bai, C., & Yen, B. L. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0071 · Cited by 251 · see citing works
The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy
Hoogduijn, M. J., Popp, F., Verbeek, R., Masoodi, M., Nicolaou, A., Baan, C., & Dahlke, M.-H. (2010) · International Immunopharmacology · doi:10.1016/j.intimp.2010.06.019 · Cited by 248 · see citing works
Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10
Yang, S., Park, M.-J., Yoon, I., Kim, S., Hong, S., Shin, J.-Y., Nam, H.-Y., Kim, Y.-H., Kim, B., & Park, C. (2009) · Experimental & Molecular Medicine · doi:10.3858/emm.2009.41.5.035 · Cited by 241 · see citing works
Nasef, A., Chapel, A., Mazurier, C., Bouchet, S., Lopez, M., Mathieu, N., Sensebé, L., Zhang, Y., Gorin, N. C., Thierry, D., et al. (2006) · Gene Expression · doi:10.3727/000000006780666957 · Cited by 227 · see citing works
CD106 Identifies a Subpopulation of Mesenchymal Stem Cells with Unique Immunomodulatory Properties
Yang, Z. X., Han, Z.-B., Ji, Y. R., Wang, Y. W., Liang, L., Chi, Y., Yang, S. G., Li, L. N., Luo, W. F., Li, J. P., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059354 · Cited by 225 · see citing works
Mesenchymal Stem Cells for Regenerative Therapy: Optimization of Cell Preparation Protocols
Ikebe, C., & Suzuki, K. (2014) · BioMed Research International · doi:10.1155/2014/951512 · Cited by 216 · see citing works
Chen, K., Wang, D., Du, W. T., Han, Z., Ren, H., Chi, Y., Yang, S. G., Zhu, D., Bayard, F., & Han, Z. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.01.015 · Cited by 201 · see citing works
Sepúlveda, J. C., Tomé, M., Fernández‐Santos, M. E., Delgado, M., Campisi, J., Bernad, A., & Gonzalez, M. A. (2014) · Stem Cells · doi:10.1002/stem.1654 · Cited by 191 · see citing works
Ramasamy, R., Tong, C. K., Seow, H. F., Vidyadaran, S., & Dazzi, F. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2008.04.009 · Cited by 191 · see citing works
Najar, M., Rouas, R., Raicevic, G., Boufker, H. I., Lewalle, P., Meuleman, N., Bron, D., Toungouz, M., Martiat, P., & Lagneaux, L. (2009) · Cytotherapy · doi:10.1080/14653240903079377 · Cited by 188 · see citing works
Optimizing mesenchymal stem cell-based therapeutics
Wagner, J., Kean, T. J., Young, R. G., Dennis, J. E., & Caplan, A. I. (2009) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2009.08.009 · Cited by 180 · see citing works
Immunosuppressive properties of cloned bone marrow mesenchymal stem cells
Xu, G., Zhang, L., Ren, G., Yuan, Z., Zhang, Y., Zhao, R. C. H., & Shi, Y. (2007) · Cell Research · doi:10.1038/cr.2007.4 · Cited by 145 · see citing works
Tobin, L. M., Healy, M. E., English, K., & Mahon, B. P. (2012) · Clinical & Experimental Immunology · doi:10.1111/cei.12056 · Cited by 126 · see citing works
Szabó, E. V., Fajka‐Boja, R., Kriston-Pál, É., Hornung, Á., Makra, I., Kudlik, G., Uher, F., Katona, R. L., Monostori, É., & Czibula, Á. (2015) · Stem Cells and Development · doi:10.1089/scd.2014.0581 · Cited by 92 · see citing works
Ivanova‐Todorova, E., Bochev, I., Dimitrov, R., Belemezova, K., Mourdjeva, M., Kyurkchiev, S., Kinov, P. S., Altankova, I., & Kyurkchiev, D. S. (2012) · BioMed Research International · doi:10.1155/2012/295167 · Cited by 85 · see citing works
Li, M., Sun, X., Kuang, X., et al. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12423 · Cited by 77 · see citing works
Fuenzalida, P., Kurte, M., Fernández-O’Ryan, C., Ibañez, C., Gauthier-Abeliuk, M., Vega-Letter, A. M., González, P. L., Irarrázabal, C. E., Quezada, N., Figueroa, F. E., et al. (2016) · Cytotherapy · doi:10.1016/j.jcyt.2016.02.002 · Cited by 49 · see citing works
Paladino, F. V., Peixoto-Cruz, J. S., Santacruz-Pérez, C., & Goldberg, A. C. (2015) · Cell and Tissue Banking · doi:10.1007/s10561-015-9525-6 · Cited by 38 · see citing works
Self-citationDonor variation in the growth properties and osteogenic potential of human marrow stromal cells
Phinney, D. G., Kopen, G. C., Righter, W., Webster, S., Tremain, N., & Prockop, D. J. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19991201)75:3 · Cited by 28 · see citing works
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- Authors
- Paladino, F. V., Sardinha, L. R., Piccinato, C. A., & Goldberg, A. C.
- Affiliations
- Universidade de São Paulo (BR)
- Hospital Israelita Albert Einstein (BR)
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
- Corresponding author
- Goldberg, Anna Carla
- Venue
- Stem Cells International
- Publisher
- Wiley
- Published
- 2017
- Volume
- 2017
- Pages
- 1-12
- ISSN
- 1687-966X (ISSN-L)
- 1687-9678
- PMC
- PMC5516721
- OpenAlex
- W2729949179
- Cited by
- 23
- References
- 59
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2022: 4 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cells International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- Wharton's jelly mesenchymal stem cells, sample-to-sample variation, immunomodulation, T cell proliferation inhibition, cytokine gene expression, replicative senescence, cell therapy, CD3+ T cells, peripheral blood mononuclear cells
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