Abstract
The possibility of isolating bovine mesenchymal multipotent stromal cells (MSCs) from fetal adnexa is an interesting prospect due to the potential use of these cells in biotechnological applications. However, little is known about the properties of these progenitor cells in bovine species. Wharton’s jelly (WJ) MSC cells were obtained from the umbilical cord of bovine fetuses at three different stages of pregnancy and divided into groups 1, 2 and 3 according to gestational trimester. Cell morphology, from the three stages of pregnancy, typically appeared fibroblast-like spindle-shaped, presenting the same viability and number. Moreover, the proliferative ability of T-cells in response to a mitogenic stimulus was suppressed when WJMSC cells were added to the culture. Multilineage properties were confirmed by their ability to undergo adipogenic, osteogenic/chondrogenic and neurogenic differentiation. Mesenchymal phenotyping, CD105+, CD29+, CD73+ and CD90+ cell markers were detected in all three cell groups, yet these markers were considered more expressed in MSCs of group 2 (p < 0.005). Expression of cytokines IL2, IL6RR, INFAC, INFB1, IFNG, TNF and LTBR were downregulated, whereas IL1F10 expression was upregulated in all tested WJMSCs. The present study demonstrated that WJMSCs harvested from the bovine umbilical cord at different gestational stages showed proliferative capacity, immune privilege and stemness potential.
Similar content being viewed by others
References
Calloni R, Viegas GS, Turck P, Bonatto D, Henriques JAP (2014) Mesenchymal stromal cells from unconventional model organisms. Cytotherapy 16:3–16
Cardoso TC, Ferrari HF, Garcia AF, Novais JB, Silva-Frade C, Ferrarezi MC, Andrade AL, Gameiro R (2012) Isolation and characterization of Wharton’s jelly derived multipotent mesenchymal stromal cells obtained from bovine umbilical cord and maintained in a define serum-free three dimensional system. BMC Biotechnol 12:18
Carlin R, Davis D, Weiss M, Schuktz B, Troyer D (2006) Expression of early transcription factor Oct-4, Sox-2 and Nanog by porcine umbilical cord (PUC) matrix cells. Reprod Biol Endrocrinol 4:8
Corradetti B, Lange-Consiglio A, Cremonesi F, Bizzaro D (2008) Isolation, in vitro culture and characterization of foetal umbilical cord stem cells at birth. Vet Res Commun 32:139–142
Corradetti B, Meuci A, Bizzaro D, Cremonesi F, Lange-Consiglio A (2013) Mesenchymal stem cells from amnion and amniotic fluid in the bovine. Reproduction 145:391–400
Corrao S, La Rocca G, Lo Iacono M, Corsello T, Farina F, Anzalone R (2013) Umbilical cord revisited: from Wharton’s jelly to mesenchymal stem cells. Histol Histopathol 28:1235–1244
Cortes Y, Ojeda M, Araya D, Dueñas F, Fernández MS, Peralta OA (2013) Isolation and multilineage differentiation of bone barrow mesenchymal stem cells from abattoir-derived bovine fetuses. BMC Vet Res 9:133
Cremonesi F, Violini S, Lange-Consiglio A, Ramelli P, Ranzenigo G, Mariani P (2008) Isolation, in vitro culture and characterization of foal umbilical cord stem cells at birth. Vet Res Commun 32:139–142
Cremonesi F, Corradetti B, Lange-Consiglio A (2011) Fetal adnexa derived stem cells from domestic animal: progress and perspectives. Theriogenology 75:1400–1415
De Miguel MP, Fuentes-Julián S, Blázquez-Martinez A, Pascual CY, Aller MA, Arias J, Arnalich-Montiel F (2012) Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 12:574–591
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2008) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for cellular therapy position statement. Cytotherapy 8:315–317
Godoy RF, Alves ALG, Gibson AJ, Lima EMM, Goodship AE (2014) Do progenitor cells from different tissue have the same phenotype? Res Vet Sci 96:454–459
Gottipamula S, Muttigi MS, Kolkundkar U, Seetharam RN (2013) Serum free media for the production of human mesenchymal stromal cells: a review. PLoS ONE 8:e74478
Iacono E, Merlo B (2015) Stem cells from foetal adnexa and fluid in domestic animals: an update on their features and clinical application. Reprod Domest Anim 50:353–364
Lu T, Huang Y, Wang H, Ma Y, Guan W (2011) Multi-lineage potential research of bone marrow-derived stromal cells (BMSCs) from cattle. Appl Biochem Biotechnol 72:21–35
Mukonoweshuro B, Brown CJF, Fisher J, Ingham E (2014) Immunogenicity of undifferentiated and differentiated allogenic mouse mesenchymal stem cells. J Tissue Eng 5:1–15
Oda Y, Tani K, Kanei T, Haraguchi T, Itamoto K, Nakazawa H, Taura Y (2013) Characterization of neuron-like cells derived from canine bone marrow stromal cells. Vet Res Commun 37:133–138
Pham PV, Truong NC, Le P T-B, Tran T D-X, Vu NB, Bui K H-T, Phan NK (2016) Isolation and proliferation of umbilical cord tissue derived mesenchymal stem cells for clinical applications. Cell Tissue Bank 72:289–302
Poncelet AJ, Vercruysse J, Saliez A, Giandlo P (2007) Although pig allogenic mesenchymal stem cells are not immunogenic in vivo, intracardiac injection elicits an immune response in vivo. Transplantation 83:783–790
Prasanna SJ, Gopalakrishnan D, Shankar RS, Vasandan AB (2010) Pro-inflammatory cytokines, IFNγ and TNFα, influence immune properties of human bone marrow and Wharton jelly mesenchymal stem cells differentially. PLoS ONE 5:e9016
Raoufi MF, Tajik P, Dehghan MM, Eini F, Barin A (2011) Isolation and differentiation of mesenchymal stem cells from bovine umbilical cord blood. Reprod Domest Anim 46:95–99
Silva CG, Martins CF, Cardoso TC, Cunha ER, Bessler HC, Martins GHL, Pivato I, Báo SN (2016) Production of bovine embryos and calves cloned by nuclear transfer using mesenchymal stem cells from amniotic fluid and adipose tissue. Cell Reprogram 18:127–136
Singh J, Mann A, Kumar D, Duban JS, Yadar PS (2013) Cultured buffalo umbilical cord matrix cells exhibit characteristics of multipotent mesenchymal stem cells. In Vitro Cell Dev Biol Anim 49:408–416
Somal A, Bhat IA, Pudey S, Pauda BS, Thakur N, Sarkar M, Chaudra V, Saikumar G, Sharma GT (2016) A comparative study of growth kinetics, in vitro differentiation potential and molecular characterization of fetal adnexa derived caprine mesenchymal stem cells. PLoS ONE 11:e015681
Taghizadeh RR, Cetrulo KJ, Cetrulo CL (2011) Wharton’s jelly stem cells: future clinical applications. Placenta 32:5311–5315
Troyer DL, Weiss ML (2008) Concise review: Wharton’s jelly-derived cells are primitive stromal cell population. Stem Cells 26:591–599
Uranio MF, Valentini L, Lange-Consiglio A, Caira M, Guaricci AC, Lábbate A, Catachio CR, Ventura M, Cremonesi F, Del Aquila ME (2011) Isolation, proliferation, cytogenetic, and molecular characterization and in vitro differentiation potency of canine stem cells from foetal adnexa: a comparative study of amniotic fluid, amnion, and umbilical cord matrix. Mol Reprod Dev 78:361–373
Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D, McIntosh KR (2008) Immune properties of human umbilical cord Wharton’s jelly-derived cells. Stem Cells 26:2865–2874
Yang C, Madhu V, Thomas C, Yang X, Du X, Dighe A, Cui Q (2015) Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide (DMSO). Cell Tissue Res 362:577–585
Acknowledgments
The authors thank the cattle owners for their cooperation in the specimen collection at slaughterhouses. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (Grants 2012/16715-4). T.C. Cardoso and E.F. Flores are recipients of CNPq (Brazilian Council for Research) funding.
Author’s contributions
TCC participated in the design of the study, performed the cell culture in all steps and flow cytometric analysis. LHO and JCB participated in the preparation of respective umbilical cords. RG and HLF participated also in the design of the study, performed the statistical analysis and drafted the manuscript. MM and EFF drafted the final version of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors indicate no conflicts of interest.
Rights and permissions
About this article
Cite this article
Cardoso, T.C., Okamura, L.H., Baptistella, J.C. et al. Isolation, characterization and immunomodulatory-associated gene transcription of Wharton’s jelly-derived multipotent mesenchymal stromal cells at different trimesters of cow pregnancy. Cell Tissue Res 367, 243–256 (2017). https://doi.org/10.1007/s00441-016-2504-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-016-2504-9