Differentiation of Umbilical Cord Derived Mesenchymal Stem Cells into Neuron-Like Cells Using Activin a and Nicotinamide

Authors

  • Darioush Bijan Nejad1 1- Dept. of Anatomical Sciences, Cellular and Molecular Research Center (CMRC), School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
  • Saeed Azandeh2 2- Dept. of Anatomical Sciences, Cellular and Molecular Research Center (CMRC), School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
  • Sadegh Saremi3 3- Dept. of Anatomical Sciences, Cellular and Molecular Research Center (CMRC), School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
  • Anneh Mohammad Gharravi4 4- Stem Cells and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.

DOI:

https://doi.org/10.22100/jkh.v11i2.1367

Keywords:

Umbilical cord, Mesenchymal stem cells, Neuron-like cells, Activin A, Nicotinamide

Abstract

Introduction: Umbilical cord derived mesenchymal stem cells (MSCs) are one of the best sources for cell-based therapies. MSCs reveal the neuronal morphology and expression of neuronal marker in differentiation conditions. The aim of the present study was to differentiate of MSCs into neuron-like cells using Activin A and nicotinamide.

Methods: Umbilical cords were cut close to the placenta  and smaller pieces (2-4 cm) of umbilical cords prepared and Wharton's jelly extracted. MSCs were isolated by an explant culture method and surface phenotype of cells analyzed by Dako flow cytometry and the FlowJo software. MSCs were then induced for osteogenic and adipogenic differentiation. Cells were exposed to neuronal differentiation condition and treated with 20 μg / ml  Activin A and 0.1% FBS for 3 days in RPMI,then with 10 mMnicotinamide, 2% B27 and 0.1% FBS for 7 days.

Results: spindle-shaped MSCs were observed after 7-10 days of explants culture. Immunophenotype of cultured MSCs were positive for mesenchymal markers such as CD105 and CD90 but negative for hematopoietic markers such as CD34 and CD45. After MSCs differentiation to the osteogenic or adipogenic lineage, lipid droplets and calcium deposition were observed. The differentiated neural-like MSCs were appeared as pyramidal nerve-like cells with neuritis.

Some of th cells. During neuronal differentiation, axon and dendritic like process  wereosbserved in some of Bipolar and mulipolarmulipolar cells. Furthermore direct synaptic like contacts were observed between cells.

Conclusion: The present study showed that Activin A and nicotinamide could induce differentiation of MSCs into neural lineage.

References

Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24:1294-301.

Ding D-C, Chang Y-H, Shyu W-C, Lin S-Z. Human umbilical cordmesenchymal stem cells: a new era for stem cell therapy. Cell Transplantation 2015;24:339-47. doi: 10.3727/096368915X686841.

Ko T-L, Fu Y-Y, Shih Y-H, Lin Y-H, Ko M-H, Fu T-W, et al. A High efficiency induction of dopaminergic cells from human umbilical mesenchymal stem cells for the treatment of hemiparkinsonian rats. Cell Transplantation 2015;24:2251-62. doi: 10.3727/096368914X685078.

Arber C, Precious SV, Cambray S, Risner-Janiczek JR, Kelly C, Noakes Z, et al. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells. Development 2015;142:1375-86. doi: 10.1242/dev.117093.

Griffin SM, Pickard MR, Orme RP, Hawkins CP, Fricker RA. Nicotinamide promotes neuronal differentiation of mouse embryonic stem cells in vitro. Neuroreport 2013;24:1041-6. doi: 10.1097/WNR.0000000000000071.

Cimadamore F, Curchoe CL, Alderson N, Scott F, Salvesen G, Terskikh AV. Nicotinamide rescues human embryonic stem cell-derived neuroectoderm from parthanatic cell death. Stem Cells 2009;27:1772-81. doi: 10.1002/stem.107.

Nazari-Shafti TZ, Bruno IG, Martinez RF, Coleman ME, Alt EU, McClure SR. High yield recovery of equine mesenchymal stem cells from umbilical cord matrix/wharton’s jelly using a semi-automated process. Methods Mol Biol 2015;1235:131-46. doi: 10.1007/978-1-4939-1785-3_12.

Azandeh S, Orazizadeh M, Hashemitabar M, Khodadadi A, Shayesteh AA, Nejad DB, et al. Mixed enzymatic-explant protocol for isolation of mesenchymal stem cells from Wharton’s jelly and encapsulation in 3D culture system. J. Biomedical Science and Engineering 2012;5:580-6. doi: 10.4236/jbise.2012.510071.

Hashemitabar M, Allahbakhshi E, Bijan-Nejad D, Nezhad Dehbashi F, Azandeh S. Isolation and characterization of mesenchymal stem cells from human umbilical cord wharton’s jelly. Jundishapur Sci Med J 2014;13:135-45.[Persian].

Zhang L, Coulson-Thomas VJ, Dong F, Chang S-H, Call MK, Kao WW. Biological function evaluation of cultured mesenchymal stem cells derived from human umbilical cord. Investigative Ophthalmology & Visual Science 2014;55:519.

Mimura S, Suga M, Liu Y, Kinehara M, Yanagihara K, Ohnuma K, et al. Synergistic effects of FGF-2 and Activin A on early neural differentiation of human pluripotent stem cells. In Vitro Cell Dev Biol Anim 2015;51:769-75. doi: 10.1007/s11626-015-9909-8.

Sekiguchi M, Hayashi F, Tsuchida K, Inokuchi K. Neuron type-selective effects of activin on development of the hippocampus. Neurosci lett 2009;452:232-7. doi: 10.1016/j.neulet.2009.01.074.

Abdipranoto‐Cowley A, Park JS, Croucher D, Daniel J, Henshall S, Galbraith S, et al. Activin A is essential for neurogenesis following neurodegeneration. Stem Cells 2009;27:1330-46. doi: 10.1002/stem.80.

Rodriguez-Martinez G, Velasco I. Activin and TGF-β effects on brain development and neural stem cells. CNS Neurol Disord Drug 2012;11:844-55.

Zhang Y, Wang J, Chen G, Fan D, Deng M. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells. Biochem Biophys Res Commun 2011;404:610-4. doi: 10.1016/j.bbrc.2010.12.014.

Published

2016-03-15

Issue

Section

Original Article(s)

How to Cite

Differentiation of Umbilical Cord Derived Mesenchymal Stem Cells into Neuron-Like Cells Using Activin a and Nicotinamide. (2016). Knowledge and Health in Basic Medical Sciences, 11(2), Page:32-37. https://doi.org/10.22100/jkh.v11i2.1367

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