Abstract
Background: The response of stem cells to paracrine factors within the host’s body plays an important role in the regeneration process after transplantation. The aim of this study was to determine the viability and paracrine factor profile of stem cells from human extracted deciduous teeth (SHED) pre-cultivated in media supplemented with either foetal bovine serum (FBS) or pooled human serum (pHS) in the presence of individual human sera (iHS).
Methods: SHED (n = 3) from passage 4 were expanded in FBS (FBS-SHED) or pHS (pHS-SHED) supplemented media until passage 7. During expansion, the proliferation of SHED was determined. Cells at passage 7 were further expanded in human serum from four individual donors (iHS) for 120 h followed by assessment of cell viability and profiling of the secreted paracrine factors.
Results: Proliferation of SHED was significantly higher (p < 0.05) in pHS supplemented media compared to FBS supplemented media. pHS-SHED also maintained their higher proliferation rate compared to FBS-SHED in the presence of iHS. In iHS supplemented media, FBS-SHED expressed significantly higher levels of SDF-1A (p < 0.05) after 24 h compared to pHS-SHED. Similar results were found for HGF (p < 0.01), LIF (p < 0.05), PDGF-BB (p < 0.05), SDF-1A (p < 0.01), and IL-10 (p < 0.05) when cell culture supernatants from FBS-SHED were profiled 120 h post-incubation.
Conclusion: SHED expanded in pHS instead of FBS have higher proliferative capacity and show an altered secretion profile. Further studies are needed to determine whether these differences could result in better engraftment and regeneration following transplantation.
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Abbreviations
- CPD:
-
cumulative population doubling time
- FBS:
-
foetal bovine serum
- FGF-2:
-
fibroblast growth factor 2
- G-CSF:
-
granulocyte colony stimulating factor
- HGF:
-
hepatocyte growth factor
- IGF-1:
-
insulin like growth factor 1
- iHS:
-
individual human sera
- IL:
-
interleukin
- ISCT:
-
International Society for Cellular Therapy
- LIF:
-
leukaemia inhibitory factor
- MSCs:
-
mesenchymal stem cells
- PDGF-BB:
-
platelet-derived growth factor BB
- pHS:
-
pooled human serum
- SCF:
-
stem cell factor
- SDF-1A:
-
stromal cell-derived factor-1A
- SHED:
-
stem cells from human extracted deciduous teeth
- VEGF:
-
vascular endothelial growth factor
References
Ahn, H. J., Lee, W. J., Kwack, K., & Kwon, Y. D. (2009). FGF2 stimulates the proliferation of human mesenchymal stem cells through the transient activation of JNK signaling. FEBS Letters, 583(17), 2922–2926.
Aldahmash, A., Haack-Sorensen, M., Al-Nbaheen, M., Harkness, L., Abdallah, B. M., & Kassem, M. (2011). Human serum is as efficient as fetal bovine serum in supporting proliferation and differentiation of human multipotent stromal (mesenchymal) stem cells in vitro and in vivo. Stem Cell Reviews, 7(4), 860–868.
Bassat, E., Mutlak, Y. E., Genzelinakh, A., Shadrin, I. Y., Baruch Umansky, K., Yifa, O., Kain, D., Rajchman, D., Leach, J., Riabov Bassat, D., Udi, Y., Sarig, R., Sagi, I., Martin, J. F., Bursac, N., Cohen, S., & Tzahor, E. (2017). The extracellular matrix protein agrin promotes heart regeneration in mice. Nature, 547(7662), 179–184.
Beutler, B. A., Milsark, I. W., & Cerami, A. (1985). Cachectin/tumor necrosis factor: Production, distribution, and metabolic fate in vivo. Journal of Immunology, 135(6), 3972–3977.
Bianchi, G., Banfi, A., Mastrogiacomo, M., Notaro, R., Luzzatto, L., Cancedda, R., & Quarto, R. (2003). Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2. Experimental Cell Research, 287(1), 98–105.
Bieback, K., Hecker, A., Schlechter, T., Hofmann, I., Brousos, N., Redmer, T., Besser, D., Kluter, H., Muller, A. M., & Becker, M. (2012). Replicative aging and differentiation potential of human adipose tissue-derived mesenchymal stromal cells expanded in pooled human or fetal bovine serum. Cytotherapy, 14(5), 570–583.
Blazquez-Prunera, A., Almeida, C. R., & Barbosa, M. A. (2017a). Human bone marrow mesenchymal stem/stromal cells preserve their immunomodulatory and chemotactic properties when expanded in a human plasma derived Xeno-free medium. Stem Cells International, 2017, 2185351.
Blazquez-Prunera, A., Diez, J. M., Gajardo, R., & Grancha, S. (2017b). Human mesenchymal stem cells maintain their phenotype, multipotentiality, and genetic stability when cultured using a defined xeno-free human plasma fraction. Stem Cell Research & Therapy, 8(1), 103.
Choi, P., & Reiser, H. (1998). IL-4: Role in disease and regulation of production. Clinical and Experimental Immunology, 113(3), 317–319.
Couper, K. N., Blount, D. G., & Riley, E. M. (2008). IL-10: The master regulator of immunity to infection. Journal of Immunology, 180(9), 5771–5777.
Cristofalo, V. J., Allen, R. G., Pignolo, R. J., Martin, B. G., & Beck, J. C. (1998). Relationship between donor age and the replicative lifespan of human cells in culture: A reevaluation. Proceedings of the National Academy of Sciences U S A, 95(18), 10614–10619.
da Silva Meirelles, L., Chagastelles, P. C., & Nardi, N. B. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of Cell Science, 119(Pt 11), 2204–2213.
Diez, J. M., Bauman, E., Gajardo, R., & Jorquera, J. I. (2015). Culture of human mesenchymal stem cells using a candidate pharmaceutical grade xeno-free cell culture supplement derived from industrial human plasma pools. Stem Cell Research & Therapy, 6, 28.
Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315–317.
dos Santos, V. T. M., Mizukami, A., Orellana, M. D., Caruso, S. R., da Silva, F. B., Traina, F., de Lima Prata, K., Covas, D. T., & Swiech, K. (2017). Characterization of human AB serum for mesenchymal stromal cell expansion. Transfusion Medicine and Hemotherapy, 44(1), 11–21.
Fattori, E., Cappelletti, M., Costa, P., Sellitto, C., Cantoni, L., Carelli, M., Faggioni, R., Fantuzzi, G., Ghezzi, P., & Poli, V. (1994). Defective inflammatory response in interleukin 6-deficient mice. The Journal of Experimental Medicine, 180(4), 1243–1250.
Fierro, F., Illmer, T., Jing, D., Schleyer, E., Ehninger, G., Boxberger, S., & Bornhauser, M. (2007). Inhibition of platelet-derived growth factor receptorbeta by imatinib mesylate suppresses proliferation and alters differentiation of human mesenchymal stem cells in vitro. Cell Proliferation, 40(3), 355–366.
Forte, G., Minieri, M., Cossa, P., Antenucci, D., Sala, M., Gnocchi, V., Fiaccavento, R., Carotenuto, F., De Vito, P., Baldini, P. M., Prat, M., & Di Nardo, P. (2006). Hepatocyte growth factor effects on mesenchymal stem cells: Proliferation, migration, and differentiation. Stem Cells, 24(1), 23–33.
Gabay, C. (2006). Interleukin-6 and chronic inflammation. Arthritis Research & Therapy, 8(Suppl 2 (2)), S3.
Gnanasegaran, N., Govindasamy, V., Simon, C., Gan, Q. F., Vincent-Chong, V. K., Mani, V., Krishnan Selvarajan, K., Subramaniam, V., Musa, S., & Abu Kasim, N. H. (2017). Effect of dental pulp stem cells in MPTP-induced old-aged mice model. European Journal of Clinical Investigation, 47(6), 403–414.
Govindasamy, V., Abdullah, A. N., Ronald, V. S., Musa, S., Ab Aziz, Z. A., Zain, R. B., Totey, S., Bhonde, R. R., & Abu Kasim, N. H. (2010). Inherent differential propensity of dental pulp stem cells derived from human deciduous and permanent teeth. Journal of Endodontia, 36(9), 1504–1515.
Haque, N., & Abu Kasim, N. H. (2017). Pooled human serum increases regenerative potential of in vitro expanded stem cells from human extracted deciduous teeth. In Advances in experimental medicine and biology (pp. 1–16). Boston: Springer US. https://doi.org/10.1007/5584_2017_74.
Haque, N., Kasim, N. H., & Rahman, M. T. (2015). Optimization of pre-transplantation conditions to enhance the efficacy of mesenchymal stem cells. International Journal of Biological Sciences, 11(3), 324–334.
Haque, N., Kasim, N. H. A., Kassim, N. L. A., & Rahman, M. T. (2017). Autologous serum supplement favours in vitro regenerative paracrine factors synthesis. Cell Proliferation, 50(4), e12354.
He, X., Ma, J., & Jabbari, E. (2010). Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1alpha from poly(lactide ethylene oxide fumarate) hydrogels. International Journal of Pharmaceutics, 390(2), 107–116.
Kalinina, N. I., Sysoeva, V. Y., Rubina, K. A., Parfenova, Y. V., & Tkachuk, V. A. (2011). Mesenchymal stem cells in tissue growth and repair. Acta Naturae, 3(4), 30–37.
Kaltschmidt, B., Kaltschmidt, C., & Widera, D. (2012). Adult craniofacial stem cells: Sources and relation to the neural crest. Stem Cell Reviews, 8(3), 658–671.
Kawada, H., Fujita, J., Kinjo, K., Matsuzaki, Y., Tsuma, M., Miyatake, H., Muguruma, Y., Tsuboi, K., Itabashi, Y., Ikeda, Y., Ogawa, S., Okano, H., Hotta, T., Ando, K., & Fukuda, K. (2004). Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood, 104(12), 3581–3587.
Khanna-Jain, R., Vanhatupa, S., Vuorinen, A., Sandor, G., Suuronen, R., Mannerstrom, B., & Miettinen, S. (2012). Growth and differentiation of human dental pulp stem cells maintained in fetal bovine serum, human serum and serum-free/Xeno-free culture media. Journal of Stem Cell Research & Therapy, 2, 4.
Kolf, C. M., Cho, E., & Tuan, R. S. (2007). Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: Regulation of niche, self-renewal and differentiation. Arthritis Research & Therapy, 9(1), 204.
Komoda, H., Okura, H., Lee, C. M., Sougawa, N., Iwayama, T., Hashikawa, T., Saga, A., Yamamoto-Kakuta, A., Ichinose, A., Murakami, S., Sawa, Y., & Matsuyama, A. (2010). Reduction of N-glycolylneuraminic acid xenoantigen on human adipose tissue-derived stromal cells/mesenchymal stem cells leads to safer and more useful cell sources for various stem cell therapies. Tissue Engineering. Part A, 16(4), 1143–1155.
Krausgrill, B., Vantler, M., Burst, V., Raths, M., Halbach, M., Frank, K., Schynkowski, S., Schenk, K., Hescheler, J., Rosenkranz, S., & Muller-Ehmsen, J. (2009). Influence of cell treatment with PDGF-BB and reperfusion on cardiac persistence of mononuclear and mesenchymal bone marrow cells after transplantation into acute myocardial infarction in rats. Cell Transplantation, 18(8), 847–853.
Lennartsson, J., & Ronnstrand, L. (2012). Stem cell factor receptor/c-Kit: From basic science to clinical implications. Physiological Reviews, 92(4), 1619–1649.
Li, C. Y., Wu, X. Y., Tong, J. B., Yang, X. X., Zhao, J. L., Zheng, Q. F., Zhao, G. B., & Ma, Z. J. (2015). Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Research & Therapy, 6(1), 55.
Li, M., Sun, X., Ma, L., Jin, L., Zhang, W., Xiao, M., & Yu, Q. (2017). SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3beta/beta-catenin pathways. Scientific Reports, 7, 40161.
Metcalf, D. (2003). The unsolved enigmas of leukemia inhibitory factor. Stem Cells, 21(1), 5–14.
Miyahara, Y., Nagaya, N., Kataoka, M., Yanagawa, B., Tanaka, K., Hao, H., Ishino, K., Ishida, H., Shimizu, T., Kangawa, K., Sano, S., Okano, T., Kitamura, S., & Mori, H. (2006). Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nature Medicine, 12(4), 459–465.
Murakami, M., Horibe, H., Iohara, K., Hayashi, Y., Osako, Y., Takei, Y., Nakata, K., Motoyama, N., Kurita, K., & Nakashima, M. (2013). The use of granulocyte-colony stimulating factor induced mobilization for isolation of dental pulp stem cells with high regenerative potential. Biomaterials, 34(36), 9036–9047.
Nakamura, S., Yamada, Y., Katagiri, W., Sugito, T., Ito, K., & Ueda, M. (2009). Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp. Journal of Endodontia, 35(11), 1536–1542.
Oikonomopoulos, A., van Deen, W. K., Manansala, A. R., Lacey, P. N., Tomakili, T. A., Ziman, A., & Hommes, D. W. (2015). Optimization of human mesenchymal stem cell manufacturing: The effects of animal/xeno-free media. Scientific Reports, 5, 16570.
Pan, S., Dangaria, S., Gopinathan, G., Yan, X., Lu, X., Kolokythas, A., Niu, Y., & Luan, X. (2013). SCF promotes dental pulp progenitor migration, neovascularization, and collagen remodeling – Potential applications as a homing factor in dental pulp regeneration. Stem Cell Reviews, 9(5), 655–667.
Park, S., Jang, H., Kim, B. S., Hwang, C., Jeong, G. S., & Park, Y. (2017). Directional migration of mesenchymal stem cells under an SDF-1alpha gradient on a microfluidic device. PLoS One, 12(9), e0184595.
Patrikoski, M., Juntunen, M., Boucher, S., Campbell, A., Vemuri, M. C., Mannerstrom, B., & Miettinen, S. (2013). Development of fully defined xeno-free culture system for the preparation and propagation of cell therapy-compliant human adipose stem cells. Stem Cell Research & Therapy, 4(2), 27.
Peters, M., Jacobs, S., Ehlers, M., Vollmer, P., Mullberg, J., Wolf, E., Brem, G., Meyer zum Buschenfelde, K. H., & Rose-John, S. (1996). The function of the soluble interleukin 6 (IL-6) receptor in vivo: Sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. Journal of Experimental Medicine, 183(4), 1399–1406.
Pierson, W., & Liston, A. (2010). A new role for interleukin-10 in immune regulation. Immunology and Cell Biology, 88(8), 769–770.
Pons, J., Huang, Y., Arakawa-Hoyt, J., Washko, D., Takagawa, J., Ye, J., Grossman, W., & Su, H. (2008). VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochemical and Biophysical Research Communications, 376(2), 419–422.
Ponte, A. L., Marais, E., Gallay, N., Langonne, A., Delorme, B., Herault, O., Charbord, P., & Domenech, J. (2007). The in vitro migration capacity of human bone marrow mesenchymal stem cells: Comparison of chemokine and growth factor chemotactic activities. Stem Cells, 25(7), 1737–1745.
Rousset, F., Garcia, E., Defrance, T., Peronne, C., Vezzio, N., Hsu, D. H., Kastelein, R., Moore, K. W., & Banchereau, J. (1992). Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proceedings of the National Academy of Sciences, 89(5), 1890–1893.
Salcedo, R., Wasserman, K., Young, H. A., Grimm, M. C., Howard, O. M., Anver, M. R., Kleinman, H. K., Murphy, W. J., & Oppenheim, J. J. (1999). Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha. The American Journal of Pathology, 154(4), 1125–1135.
Sloan, A. J., & Waddington, R. J. (2009). Dental pulp stem cells: What, where, how? International Journal of Paediatric Dentistry, 19(1), 61–70.
Son, B. R., Marquez-Curtis, L. A., Kucia, M., Wysoczynski, M., Turner, A. R., Ratajczak, J., Ratajczak, M. Z., & Janowska-Wieczorek, A. (2006). Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells, 24(5), 1254–1264.
Sulpice, E., Ding, S., Muscatelli-Groux, B., Berge, M., Han, Z. C., Plouet, J., Tobelem, G., & Merkulova-Rainon, T. (2009). Cross-talk between the VEGF-A and HGF signalling pathways in endothelial cells. Biology of the Cell, 101(9), 525–539.
Tamama, K., Fan, V. H., Griffith, L. G., Blair, H. C., & Wells, A. (2006). Epidermal growth factor as a candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells, 24(3), 686–695.
Trounson, A., & McDonald, C. (2015). Stem cell therapies in clinical trials: Progress and challenges. Cell Stem Cell, 17(1), 11–22.
Turnovcova, K., Ruzickova, K., Vanecek, V., Sykova, E., & Jendelova, P. (2009). Properties and growth of human bone marrow mesenchymal stromal cells cultivated in different media. Cytotherapy, 11(7), 874–885.
van de Kamp, J., Paefgen, V., Woltje, M., Bobel, M., Jaekel, J., Rath, B., Labude, N., Knuchel, R., Jahnen-Dechent, W., & Neuss, S. (2017). Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor-loaded biomaterials. Journal of Tissue Engineering and Regenerative Medicine, 11(11), 2988–2998.
Vunjak-Novakovic, G., & Scadden, D. T. (2011). Biomimetic platforms for human stem cell research. Cell Stem Cell, 8(3), 252–261.
Wagers, A. J. (2012). The stem cell niche in regenerative medicine. Cell Stem Cell, 10(4), 362–369.
Wang, Y., Johnsen, H. E., Mortensen, S., Bindslev, L., Ripa, R. S., Haack-Sorensen, M., Jorgensen, E., Fang, W., & Kastrup, J. (2006). Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention. Heart, 92(6), 768–774.
Wang, X., Sha, X. J., Li, G. H., Yang, F. S., Ji, K., Wen, L. Y., Liu, S. Y., Chen, L., Ding, Y., & Xuan, K. (2012). Comparative characterization of stem cells from human exfoliated deciduous teeth and dental pulp stem cells. Archives of Oral Biology, 57(9), 1231–1240.
Werner, S., & Grose, R. (2003). Regulation of wound healing by growth factors and cytokines. Physiological Reviews, 83(3), 835–870.
Williams, A. R., Suncion, V. Y., McCall, F., Guerra, D., Mather, J., Zambrano, J. P., Heldman, A. W., & Hare, J. M. (2013). Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. Journal of the American Heart Association, 2(3), e000140.
Yanada, S., Ochi, M., Kojima, K., Sharman, P., Yasunaga, Y., & Hiyama, E. (2006). Possibility of selection of chondrogenic progenitor cells by telomere length in FGF-2-expanded mesenchymal stromal cells. Cell Proliferation, 39(6), 575–584.
Yim, H., Jeong, H., Cho, Y., Jeong, S., & Oh, I. (2016). Safety of mesenchymal stem cell therapy: A systematic review and meta-analysis. Cytotherapy, 18(6), S77–S77.
Youn, S. W., Lee, S. W., Lee, J., Jeong, H. K., Suh, J. W., Yoon, C. H., Kang, H. J., Kim, H. Z., Koh, G. Y., Oh, B. H., Park, Y. B., & Kim, H. S. (2011). COMP-Ang1 stimulates HIF-1alpha-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood, 117(16), 4376–4386.
Yu, Q., Liu, L., Lin, J., Wang, Y., Xuan, X., Guo, Y., & Hu, S. (2015). SDF-1α/CXCR4 axis mediates the migration of mesenchymal stem cells to the hypoxic-ischemic brain lesion in a rat model. Cell Journal (Yakhteh), 16(4), 440–447.
Yubo, M., Yanyan, L., Li, L., Tao, S., Bo, L., & Lin, C. (2017). Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment: A meta-analysis. PLoS One, 12(4), e0175449.
Acknowledgement
This work was supported by High Impact Research MOHE Grant UM.C/625/1/HIR/MOHE/DENT/01 from the Ministry of Higher Education Malaysia and University of Malaya Research Grant UMRG RP019/13HTM. The authors thank the staff nurses from the Oro-Maxillofacial Surgical and Medical Sciences Department, Faculty of Dentistry, University of Malaya, for their support in collection of blood from donors.
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The authors declare no conflicts of interest.
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Haque, N., Widera, D., Abu Kasim, N.H. (2018). Stem Cells from Human Extracted Deciduous Teeth Expanded in Foetal Bovine and Human Sera Express Different Paracrine Factors After Exposure to Freshly Prepared Human Serum. In: Pham, P. (eds) Tissue Engineering and Regenerative Medicine. Advances in Experimental Medicine and Biology(), vol 1084. Springer, Cham. https://doi.org/10.1007/5584_2018_299
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