Skip to main content
SpringerLink
Log in

Induction of human umbilical Wharton’s jelly-derived mesenchymal stem cells toward motor neuron-like cells

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

The most important property of stem cells from different sources is the capacity to differentiate into various cells and tissue types. However, problems including contamination, normal karyotype, and ethical issues cause many limitations in obtaining and using these cells from different sources. The cells in Wharton’s jelly region of umbilical cord represent a pool source of primitive cells with properties of mesenchymal stem cells (MSCs). The aim of this study was to determine the potential of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) for differentiation to motor neuron cells. WJMSCs were induced to differentiate into motor neuron-like cells by using different signaling molecules and neurotrophic factors in vitro. Differentiated neurons were then characterized for expression of motor neuron markers including nestin, PAX6, NF-H, Islet 1, HB9, and choline acetyl transferase (ChAT) by quantitative reverse transcription PCR and immunocytochemistry. Our results showed that differentiated WJMSCs could significantly express motor neuron biomarkers in RNA and protein levels 15 d post induction. These results suggested that WJMSCs can differentiate to motor neuron-like cells and might provide a potential source in cell therapy for neurodegenerative disease.

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

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.

Similar content being viewed by others

References

  • Asmani MN, Ai J, Amoabediny G, Noroozi A, Azami M, Ebrahimi-Barough S, Navaei-Nigjeh M, Ai A, Jafarabadi M (2013) Three dimensional culture of differentiated endometrial stromal cells to oligodendrocyte progenitor cells (OPCs) in fibrin hydrogel. Cell Biol Int 37(12):1340–1349

    Article  CAS  PubMed  Google Scholar 

  • Can A, Karahuseyinoglu S (2007) Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 25(11):2886–2895

    Article  PubMed  Google Scholar 

  • Carvalho MM, Teixeira FG, Reis RL, Sousa N, Salgado AJ (2011) Mesenchymal stem cells in the umbilical cord: phenotypic characterization, secretome and applications in central nervous system regenerative medicine. Curr Stem Cell Res Ther 6(3):221–228

    Article  CAS  PubMed  Google Scholar 

  • Dhara SK, Stice SL (2008) Neural differentiation of human embryonic stem cells. J Cell Biochem 105:633–640

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221

    Article  CAS  PubMed  Google Scholar 

  • Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457(7227):277–280

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ebrahimi-Barough S, Massumi M, Kouchesfahani HM, Ai J, Massumi M, Mohammad (2013a) Derivation of pre oligodendrocytes from human endometrial stromal cells by using overexpression of microRNA 338. J Mol Neurosci 51(2):337–343

    Article  CAS  PubMed  Google Scholar 

  • Ebrahimi-Barough S, Kouchesfahani HM, Ai J, Massumi M (2013b) Differentiation of human endometrial stromal cells into oligodendrocyte progenitor cells (OPCs). J Mol Neurosci 51(2):265–273

  • Ebrahimi-Barough S, Javidan JA, Saberi H, Joghataei MT, Rahbarghazi R, Mirzaei E, Faghihi F, Shirian S, Ai A, Ai J (2014) Evaluation of motor Neuron-like cell differentiation of hEnSCs on biodegradable PLGA nanofiber Scaffolds. Mol Neurobiol. doi: 10.1007/s12035-014-8931-2

  • Ebrahimi-Barough S, Hoveizi E, Norouzi Javidan A, Ai J (2015) Investigating the neuroglial differentiation effect of neuroblastoma conditioned medium in human endometrial stem cells cultured on 3D nanofibrous scaffold. doi: 10.1002/jbm.a.35397

  • Ericson J, Rashbass P, Schedl A, Brenner-Morton S, Kawakami A, van Heyningen V, Jessell TM, Briscoe J (1997) Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90(1):169–180

    Article  CAS  PubMed  Google Scholar 

  • Forraz N, McGuckin CP (2011) The umbilical cord: a rich and ethical stem cell source to advance regenerative medicine. Cell Prolif 44(1):60–69

    Article  PubMed  Google Scholar 

  • Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC, Shih YH, Ko MH, Sung MS (2006) Conversion of human umbilical cord mesechymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for parkinsonism. Stem Cell 24(1):115–124

    Article  Google Scholar 

  • Harper JM, Krishnan C, Darman JS, Deshpande DM, Peck S, Shats I, Backovic S, Rothstein JD, Kerr DA (2004) Axonal growth of embryonic stem cellderivedmotoneurons in vitro and in motoneuron-injured adult rats. Proc Natl Acad Sci U S A 101(18):7123–7128

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hass R, Kasper C, Böhm S, Jacobs R (2011) Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Comm Signal 9:12

    Article  CAS  Google Scholar 

  • Hendrickson ML, Rao AJ, Demerdash ON, Kalil RE (2011) Expression of nestin by neural cells in the adult rat and human brain. PLoS One 6(4), e18535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jiang J, Lv Z, Gu Y, Li J, Xu L, Xu W, Lu J, Xu J (2010) Adult rat mesenchymal stem cells differentiate into neuronal-like phenotype and express a variety of neuro-regulatory molecules in vitro. Neurosci Res 66(1):46–52

    Article  CAS  PubMed  Google Scholar 

  • La Rocca G, Anzalone R, Corrao S, Magno F, Loria T, Lo Iacono M, Di Stefano A, Giannuzzi P, Marasà L, Cappello F, Zummo G, Farina F (2009) Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochem Cell Biol 131(2):267–282

    Article  PubMed  Google Scholar 

  • Lee G, Kim H, Elkabetz Y, Al Shamy G, Panagiotakos G, Barberi T, Tabar V, Studer L (2007) Isolation and directed differentiation of neural crest stem cells derived from human embryonic stem cells. Nat Biotechnol 25(12):1468–1475

    Article  CAS  PubMed  Google Scholar 

  • Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang SC (2005) Specification of motoneurons from human embryonic stem cells. Nat Biotechnol 23(2):215–221

    Article  PubMed  Google Scholar 

  • Liqing Y, Jia G, Jiqing C, Ran G, Fei C, Jie K, Yanyun W, Cheng Z (2011) Directed differentiation of motor neuron cell-like cells from human adipose-derived stem cells in vitro. Neuroreport 22(8):370–373

    Article  PubMed  Google Scholar 

  • Lopez-Gonzalez R, Velasco I (2012) Therapeutic potential of motor neurons differentiated from embryonic stem cells and induced pluripotent stem cells. Arch Med Res 43(1):1–10

    Article  PubMed  Google Scholar 

  • Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL (2011) Stem cell technology for the study and treatment of motor neuron diseases. 6(2):201-213

  • Ma L, Feng XY, Cui BL, Law F, Jiang XW, Yang LY, Xie QD, Huang TH (2005) Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells differentiation into nerve-like cells. Chin Med J (Engl) 118(23):1987–1993

    CAS  Google Scholar 

  • Mansergh FC, Wride MA, Rancourt DE (2000) Neurons from stem cells: implications for understanding nervous system development and repair. Biochem Cell Biol 78(5):613–628

    Article  CAS  PubMed  Google Scholar 

  • Miles GB, Yohn DC, Wichterle H, Jessell TM, Rafuse VF, Brownstone RM (2004) Functional properties of motoneurons derived from mouse embryonic stem cells. J Neurosci 24(36):7848–7858

    Article  CAS  PubMed  Google Scholar 

  • Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, Helwig B, Beerenstrauch M, Abou-Easa K, Hildreth T, Troyer D, Medicetty S (2003) Matrix cells from Wharton's jelly from neurons and glia. Stem Cells 21(1):50–60

    Article  CAS  PubMed  Google Scholar 

  • Mobarakeh ZT, Ai J, Yazdani F, Sorkhabadi SM, Ghanbari Z, Javidan AN, Mortazavi- Tabatabaei SA, Massumi M, Barough SE (2012) Human endometrial stem cells as a new source for programming to neural cells. Cell Biol Inter Rep 19(1):7–14

    Article  Google Scholar 

  • Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M (2010) Optimization and scale-up of Wharton’s jelly-derived mesenchymal stem cells for clinical applications. Stem Cell Res 5(3):244–254

    Article  CAS  PubMed  Google Scholar 

  • Qi Y, Zhang F, Song G, Sun X, Jiang R, Chen M, Ge J (2010) Cholinergic neuronal differentiation of bone marrow mesenchymal stem cells in rhesus monkeys. Sci China Life Sci 53(5):573–580

    Article  CAS  PubMed  Google Scholar 

  • Qu Q, Li D, Louis KR, Li X, Yang H, Sun Q, Crandall SR, Tsang S, Zhou J, Cox CL, Cheng J, Wang F (2014) High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1. Nat Commun 13(5):3449

    Google Scholar 

  • Romanov YA, Svintsitskaya VA, Smirnov VN (2003) Searching for alternative source of postnatal human mesenchymal stem cells; candidate MSC-like cells from umbilical cord. Stem Cells 21(1):105–110

    Article  PubMed  Google Scholar 

  • Shen WC, Liang CJ, Wu VC, Wang SH, Young GH, Lai IR, Chien CL, Wang SM, Wu KD, Chen YL (2013) Endothelial progenitor cells derived from Wharton’s jelly of the umbilical cord reduces ischemia-induced hind limb injury in diabetic mice by inducing HIF-1α/IL-8 expression. Stem Cells Dev 22(9):1408–1418

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shin S, Dalton S, Stice SL (2005) Human motor neuron differentiation from human embryonic stem cells. Stem Cells Dev 14(3):266–269

    Article  CAS  PubMed  Google Scholar 

  • Tam RY, Fuehrmann T, Mitrousis N, Shoichet MS (2014) Regenerative therapies for central nervous system diseases: a biomaterials approach. Neuropsychopharmacology 39(1):169–188

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Trivanović D, Kocić J, Mojsilović S, Krstić A, Ilić V, Djordjević IO, Santibanez JF, Jovcić G, Terzić M, Bugarski D (2013) Mesenchymal stem cells isolated from peripheral blood and umbilical cord Wharton’s jelly. Srp Arh Celok Lek 141(3–4):178–186

    Article  PubMed  Google Scholar 

  • Wichterle H, Lieberam I, Porter JA, Jessell TM (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110(3):385–397

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The author wish to thank Iranian National Science Foundation (grant number 91001166) and Iran University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Zohreh Bagher, Mansooreh Soleimani & Mohammad Taghi Joghataei

  2. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Somayeh Ebrahimi-Barough, Mahmoud Azami & Jafar Ai

  3. Polymer Engineering Faculty, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran

    Hamid Mirzadeh

  4. Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mansooreh Soleimani

  5. Tissue Engineering Division, Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mohammad Reza Nourani

  6. Department of Anatomy, School of Medicine, Iran University of Medical Science, Tehran, Iran

    Mohammad Taghi Joghataei

  7. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran

    Mansooreh Soleimani & Mohammad Taghi Joghataei

Authors
  1. Zohreh Bagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Somayeh Ebrahimi-Barough
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahmoud Azami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamid Mirzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mansooreh Soleimani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jafar Ai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammad Reza Nourani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Taghi Joghataei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Taghi Joghataei.

Additional information

Editor: T. Okamoto

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bagher, Z., Ebrahimi-Barough, S., Azami, M. et al. Induction of human umbilical Wharton’s jelly-derived mesenchymal stem cells toward motor neuron-like cells. In Vitro Cell.Dev.Biol.-Animal 51, 987–994 (2015). https://doi.org/10.1007/s11626-015-9921-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-015-9921-z

Keywords

Search

Navigation