Skip to main content

Advertisement

SpringerLink
Log in

Differentiation potential of different regions-derived same donor human Wharton’s jelly mesenchymal stem cells into functional smooth muscle-like cells

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The present study evaluates the transdifferentiation potential of different region-derived same donor Wharton’s jelly MSCs (WJMSCs) into functional smooth muscle-like cells (SMLCs). All regions showed baseline expression for early smooth muscle cell (SMC) markers (αSMA and SM22-α) whereas mid marker CALPONIN gradually reduced during in vitro culture expansion and late marker myosin heavy chain type-11 (MHY-11) was completely absent. Furthermore, WJMSCs were induced to SMLCs using DMEM containing 10% FBS supplemented with different concentrations/combinations of TGF-β1 and PDGF-BB under normoxia (20% O2) condition. Three treatment groups namely group A: 2.5 ng/ml TGF-β1, group B: 5 ng/ml PDGF-BB and group C: 2.5 ng/ml TGF-β1 + 5 ng/ml PDGF-BB were used for the induction of WJMSCs into SMLCs. Cells were evaluated for SMC-specific marker expression at different time intervals. Finally, selection of the SMC-specific highly potent region along with the most suitable treatment group was done on the basis of highest outcome in terms of SMC-specific marker expression and functional competence of transdifferentiated cells. Among all regions, baby region-derived WJMSCs (B-WJMSCs) exhibited highest SMC marker expression and functional ability. To mimic the in vivo physiological conditions, hypoxic conditions (3% O2) were used to evaluate the effect of low oxygen on the SMLC differentiation potential of selected WJMSCs using previously used same parameters. Annexin-V assay was performed to check the effect of cytokines and different oxygen concentrations, which revealed no significant differences. It was concluded that different induction conditions have different but positive effects on the functional SMLC differentiation ability of WJMSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

WJMSCs:

Wharton’s jelly mesenchymal stem cells

SMLCs:

smooth muscle-like cells

SMC:

smooth muscle cell

α-SMA:

alpha smooth muscle actin

SM22-α:

alpha-smooth muscle 22

MHY-11:

myosin heavy chain 11

References

  • Andersson KE, Arner A (2004) Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 84:935–986

    Article  CAS  PubMed  Google Scholar 

  • Bharti D, Shivakumar SB, Park JK, Ullah I, Subbarao RB, Park JS, Lee SL, Park BW, Rho GJ (2017) Comparative analysis of human Wharton’s jelly mesenchymal stem cells derived from different parts of the same umbilical cord. Cell Tissue Res 372:51–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corrao S, La Rocca G, Lo Iacono M, Corsello T, Farina F, Anzalone R (2013) Umbilical cord revisited: from Wharton’s jelly myofibroblasts to mesenchymal stem cells. Histol Histopathol 28:1235–1244

    PubMed  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Dj P, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther Pos Statement Cytother 8:315–317

    CAS  Google Scholar 

  • Ghionzoli M, Repele A, Sartiani L, Costanzi G, Parenti A, Spinelli V, David AL, Garriboli M, Totonelli G, Tian J, Andreadis ST, Cerbai E, Mugelli A, Messineo A, Pierro A, Eaton S, De Coppi P (2013) Human amniotic fluid stem cell differentiation along smooth muscle lineage. FASEB J 27:4853–4865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo X, Stice SL, Boyd NL, Chen SY (2013) A novel in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells. Am J Physiol Cell Physiol 304:C289–C298

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi K, Kubota T, Aso T (1998) Study on myofibroblast differentiation in the stromal cells of Wharton’s jelly: expression and localization of alpha-smooth muscle actin. Early Hum Dev 51:223–233

    Article  CAS  PubMed  Google Scholar 

  • Moonen JR, Krenning G, Brinker MG, Koerts JA, van Luyn MJ, Harmsen MC (2010) Endothelial progenitor cells give rise to pro-angiogenic smooth muscle-like progeny. Cardiovasc Res 86:506–515

    Article  CAS  PubMed  Google Scholar 

  • Ngo P, Ramalingam P, Phillips JA, Furuta GT (2006) Collagen gel contraction assay. Methods Mol Biol 341:103–109

    CAS  PubMed  Google Scholar 

  • Rodríguez LV, Alfonso Z, Zhang R, Leung J, Wu B, Ignarro LJ (2006) Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells. Proc. Natl Acad Sci USA 103:12167–12172

    Article  CAS  Google Scholar 

  • Ross JJ, Hong Z, Willenbring B, Zeng L, Isenberg B, Eu HL, Reyes M, Keirstead SA, Weir EK, Tranquillo RT, Verfaillie CM (2006) Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells. J Clin Invest 116:3139–3149

    Article  PubMed  PubMed Central  Google Scholar 

  • Shivakumar SB, Bharti D, Jang SJ, Hwang SC, Park JK, Shin JK, Byun JH, Park BW, Rho GJ (2015) Cryopreservation of human Wharton’s jelly-derived mesenchymal stem cells following controlled rate freezing protocol using different Cryoprotectants; a comparative study. Int J Stem Cells 8:155–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shivakumar SB, Bharti D, Subbarao RB, Jang SJ, Park JS, Ullah I, Park JK, Byun JH, Park BW, Rho GJ (2016) DMSO- and serum-free cryopreservation of Wharton’s jelly tissue isolated from human umbilical cord. J Cell Biochem 117:2397–2412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song B, Jiang W, Alraies A, Liu Q, Gudla V, Oni J, Wei X, Sloan A, Ni L, Agarwal M (2016) Bladder smooth muscle cells differentiation from dental pulp stem cells: future potential for bladder tissue engineering. Stem Cells Int 2016:6979368. https://doi.org/10.1155/2016/6979368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subramanian A, Fong CY, Biswas A, Bongso A (2015) Comparative characterization of cells from the various compartments of the human umbilical cord shows that the Wharton’s jelly compartment provides the best source of clinically utilizable mesenchymal stem cells. PLoS One 10:e0127992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takechi K, Kuwabara Y, Mizuno M (1993) Ultrastructural and immunohistochemical studies of Wharton’s jelly umbilical cord cells. Placenta 14:235–245

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Yin S, Cen L, Liu Q, Liu W, Cao Y, Cui L (2010) Differentiation of adipose-derived stem cells into contractile smooth muscle cells induced by transforming growth factor-beta1 and bone morphogenetic protein-4. Tissue Eng. Part A 16:1201–1213

    CAS  Google Scholar 

  • Wanjare M, Kuo F, Gerecht S (2013) Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells. Cardiovasc Res 97:321–330

    Article  CAS  PubMed  Google Scholar 

  • Xu ZC, Zhang Q, Li H (2013) Human hair follicle stem cell differentiation into contractile smooth muscle cells is induced by transforming growth factor-β1 and platelet-derived growth factor BB. Mol Med Rep 8:1715–1721

    Article  CAS  PubMed  Google Scholar 

  • Xu JG, Zhu SY, Heng BC, Dissanayaka WL, Zhang CF (2017) TGF-β1 induced differentiation of SHED into functional smooth muscle cells. Stem Cell Res Ther 8:1–10

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are highly thankful to Professor BW Park, Doctor Ji-Eun Park and Doctor Ji-Kwon Park for providing valuable human whole umbilical cord samples. We also acknowledge Professor Dawon Kang for helping us with the electrophysiology experiments.

Funding

This study was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1596) and a grant from the National Research Foundation (NRF-2016R1D1A3B03932491 and Stem Centric Co. Ltd., Republic of Korea.

Author information

Authors and Affiliations

  1. Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 900 Gajwa, Jinju, 660-701, Republic of Korea

    Dinesh Bharti, Sharath Belame Shivakumar, Young-Bum Son, Young-Ho Choi, Hyeon-Jeong Lee, Sung-Lim Lee & Gyu-Jin Rho

  2. Animal Biotechnology Division, National Institute of Animal Science, RDA, 1500 Kongjwipatjwi-ro Isero-myeon, Wanju-gun, Jeollabuk-do, 565-851, Republic of Korea

    Imran Ullah & Sun-A Ock

  3. Department of Physiology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 660-751, Republic of Korea

    Eun-Jin Kim & Dawon Kang

  4. Department of Obstetrics and Gynecology, School of Medicine, Gyeongsang National University, Changwon, Republic of Korea

    Ji-Eun Park & Ji-Kwon Park

  5. Department of Oral and Maxillofacial Surgery, School of Medicine, Gyeongsang National University, Changwon, Republic of Korea

    Bong-Wook Park

  6. Research Institute of Life Sciences, Gyeongsang National University, Jinju, Republic of Korea

    Gyu-Jin Rho

Authors
  1. Dinesh Bharti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharath Belame Shivakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young-Bum Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young-Ho Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Imran Ullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyeon-Jeong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eun-Jin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sun-A Ock
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ji-Eun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ji-Kwon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dawon Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sung-Lim Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Bong-Wook Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Gyu-Jin Rho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gyu-Jin Rho.

Ethics declarations

Competing interest

The authors declare that they have no competing interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bharti, D., Shivakumar, S.B., Son, YB. et al. Differentiation potential of different regions-derived same donor human Wharton’s jelly mesenchymal stem cells into functional smooth muscle-like cells. Cell Tissue Res 377, 229–243 (2019). https://doi.org/10.1007/s00441-019-03009-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-019-03009-7

Keywords

Search

Navigation