Mesenchymal stem cells (MSCs) have the potential to differentiate into neuron-like cells, which may provide a new strategy for the clinical treatment of neurodegenerative diseases such as Parkinson's disease (PD). However, the application of MSCs in the patients is still limited as the reason of efficiency and safety of transplantation. The aim of this study is to develop a new method and induce human umbilical cord MSCs (hUCMSCs) into neuron-like cells. Results from flow cytometry indicate that the isolated MSCs from hUCMSCs exhibited a typical phenotype of adult stem cells and express CD44, CD54, CD73, CD90, CD105, CD166, and HLA-ABC. Furthermore, the induced cells from hUCMSCs could spontaneously express different neural cell markers [neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP)], even transcription factors related to dopaminergic neuron's development (Nurr1, Wnt-1, and En-1). Moreover, after treatment of EHFBT (extracts of human fetal brain tissue), hUCMSCs can express neuronal markers such as Nestin, LIM homeobox transcription factor 1 beta (LMX1B), dopamine beta hydroxylase (DBH), and dopamine transporter (DAT). In summary, a method that can induce hUCMSCs into dopaminergic neuron containing cells is established in vitro by the treatment of EHFBT. This would provide us a new cell source for PD in clinical treatment in the future.
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References
1.
BarkerR.A., Drouin-OuelletJ., and ParmarM. (2015). Cell-based therapies for Parkinson disease—Past insights and future potential. Nat. Rev. Neurol. 11, 492–503.
2.
CampeauL., SolerR., SittadjodyS., ParetaR., NomiyaM., ZarifpourM., OparaE.C., YooJ.J., and AnderssonK.E. (2014). Effects of allogeneic bone marrow derived mesenchymal stromal cell therapy on voiding function in a rat model of Parkinson disease. J. Urol. 191, 850–859.
3.
ChenX., KatakowskiM., LiY., LuD., WangL., ZhangL., ChenJ., XuY., GautamS., MahmoodA., and ChoppM. (2002). Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: Growth factor production. J. Neurosci. Res. 69, 687–691.
4.
ChevallierN., AnagnostouF., ZilberS., BodivitG., MaurinS., BarraultA., BierlingP, HernigouP., and LayrolleP., RouardH. (2010). Osteoblastic differentiation of human mesenchymal stem cells with platelet lysate. Biomaterials, 31, 270–278.
5.
ChoM.S, HwangD.Y., and KimD.W. (2008). Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat. Protoc. 3, 1888–1894.
6.
ChoongP.F., MokP.L., CheongS.K., LeongC.F., and ThenK.Y. (2007). Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy, 9, 170–183.
7.
EndeN., and ChenR. (2001). Human umbilical cord blood cells ameliorate Huntington's disease in transgenic mice. J. Med. 32, 231–240.
8.
EndeN., ChenR., and Ende-HarrisD. (2001). Human umbilical cord blood cells ameliorate Alzheimer's disease in transgenic mice. J. Med. 32, 241–247.
9.
FreedC.R., GreeneP.E., BreezeR.E., TsaiW.Y., DuMouchelW., KaoR., DillonS., WinfieldH., CulverS., and TrojanowskiJ.Q. (2001). Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N. Engl. J. Med, 344, 710–719.
10.
GazdicM., VolarevicV., ArsenijevicN., and StojkovicM. (2015). Mesenchymal stem cells: A friend or foe in immune-mediated diseases. Stem Cell Rev. 11, 280–287.
11.
GeD., LiuX., LiL., WuJ., TuQ., ShiY., and ChenH. (2009). Chemical and physical stimuli induce cardiomyocyte differentiation from stem cells. Biochem. Biophys. Res. Commun. 381, 317–321.
12.
GuineyS.J., AdlardP.A., BushA.I., FinkelsteinD.I., and AytonS. (2017). Ferroptosis and cell death mechanisms in Parkinson's disease. Neurochem. Int. 104, 34–48.
13.
HashemianS.J., KouhnavardM., Nasli-EsfahaniE. (2015). Mesenchymal stem cells: Rising concerns over their application in treatment of type one diabetes mellitus. J. Diabetes Res. 2015,675103.
14.
JaimeK., LaisO., and SusanH.F. (2018). Update in therapeutic strategies for Parkinson's disease. Curr. Opin. Neurol. 31, 439–447.
15.
KimJ.H., AuerbachJ.M., Rodríguez-GómezJ.A., VelascoI., GavinD., LumelskyN., LeeS.H., NguyenJ., Sánchez-PernauteR., BankiewiczK., and McKayR. (2002). Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’ disease. Nature, 418, 50–56.
16.
KimE.S., KimG.H., KangM.L., KangY.M., KangK.N., HwangK.C., MinB.H., KimJ.H, and KimM.S. (2011). Potential induction of rat muscle-derived stem cells to neural-like cells by retinoic acid. J. Tissue Eng. Regen. Med. 5, 410–414.
17.
LigeL., and ZengminT. (2016). Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Turk. Neurosurg. 26, 378–383.
18.
LiuT.Y., ZhangC., XiaoL.L., YaoX.L., FengS.W., and ZengY. (2005). Induced differentiation of human cord blood monocytes into neuron-like cells in vitro. J. First Mil. Med. Univ. 25, 152–155.
19.
LiuY., NiuR., YangF., YanY., LiangS., SunY., ShenP., and LinJ. (2018). Biological characteristics of human menstrual blood-derived endometrial stem cells. J. Cell Mol. Med. 22, 1627–1639.
20.
LuP., BleschA., and TuszynskiM.H. (2004). Induction of bone marrow stromal cells to neurons: Differentiation, transdifferentiation, or artifact? J. Neurosci. Res. 77, 174–191.
21.
MaK., FoxL., ShiG., ShenJ., LiuQ., PappasJ.D., ChengJ., and QuT. (2011). Generation of neural stem cell-like cells from bone marrow-derived human mesenchymal stem cells. Neurol. Res. 33, 1083–1093.
22.
MendesF.D., RibeiroP.D.C., OliveiraL.F., de PaulaD.R.M., CapuanoV., de AssunçãoT.S.F., and daSilva. V.J.D. (2018). Therapy with mesenchymal stem cells in Parkinson disease: History and perspectives. Neurologist, 23, 141–147.
23.
MiY., GaoX., XuH., CuiY., ZhangY., and GouX. (2019). The emerging roles of Ferroptosis in Huntington's disease. Neuromol. Med. 21, 110–119.
24.
MorrisG., BerkM., CarvalhoA.F., MaesM., WalkerA.J., and PuriB.K. (2018). Why should neuroscientists worry about iron? The emerging role of Ferroptosis in the pathophysiology of neuroprogressive diseases. Behav. Brain Res. 341, 154–175.
PeránM., MarchalJ.A., LópezE., Jiménez-NavarroM., BoulaizH., Rodríguez-SerranoF., CarrilloE., Sánchez-EspinG., de TeresaE., ToshD., and AranegaA. (2010). Human cardiac tissue induces transdifferentiation of adult stem cells towards cardiomyocytes. Cytotherapy, 12, 332–337.
27.
PrakashN, and WurstW. (2006) Genetic networks controlling the development of midbrain dopaminergic neurons. J. Physiol. 575(Pt 2), 403–410.
28.
Sanchez-RamosJ., SongS., Cardozo-PelaezF., HazziC., StedefordT., WillingA., FreemanT.B., SaportaS., JanssenW., PatelN., CooperD.R., and SanbergP.R. (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp. Neurol. 164, 247–256.
29.
Sanchez-RamosJR. (2002). Neural cells derived from adult bone marrow and umbilical cord blood. J. Neurosci. Res. 69, 880–893.
30.
SarkanenJ.R., KailaV., MannerströmB., RätyS., KuokkanenH., MiettinenS., and YlikomiT. (2012). Human adipose tissue extract induces angiogenesis and adipogenesis in vitro. Tissue Eng. Part A, 18, 17–25.
31.
SunJ., AllisonJ., McLaughlinC., SledgeL., Waters-PickB., WeaseS., and KurtzbergJ. (2010). Differences in quality between privately and publicly banked umbilical cord blood units: A pilot study of autologous cord blood infusion in children with acquired neurologic disorders. Transfusion, 50, 1980–1987.
32.
TondreauT., LagneauxL., DejeneffeM., MassyM., MortierC., DelforgeA., and BronD. (2004). Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation. Differentiation, 72, 319–326.
33.
TsengP.Y., ChenC.J., SheuC.C., YuC.W., and HuangY.S. (2007). Spontaneous differentiation of adult rat marrow stromal cells in a long-term cultures. J. Vet. Med. Sci. 62, 95–102.
34.
UccelliA., MorettaL., and PistoiaV. (2008). Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 8, 726–736.
35.
UndaleA.H., WestendorfJ.J., YaszemskiM.J., and KhoslaS. (2009). Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin. Proc. 84, 893–902.
36.
WoodburyD., SchwarzE.J., ProckopD.J., and BlackI.B. (2000). Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61, 364–370.
