Abstract
Parkinson’s Disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Though significant insights into the molecular-biochemical-cellular-behavioral basis of PD have been understood, there is no appreciable treatment available till date. Current therapies provide symptomatic relief without any influence on the progression of the disease. Stem cell therapy has been vigorously explored to treat PD. In this comprehensive review, we analyze various stem cell candidates for treating PD and discuss the possible mechanisms. We advocate the advantage of using neural crest originated Dental Pulp Stem Cells (DPSC) due to their predisposition towards neural differentiation and their potential to regenerate neurons far better than commonly used bone marrow derived mesenchymal stem cells (BM-MSCs). Eventually, we highlight the current challenges in the field and the strategies, which may be used for overcoming the impediments.
Keywords: Parkinson’s disease, stem cells, Dental Pulp, neuroprotection, exosomes, BM-MSC.
Graphical Abstract
[http://dx.doi.org/10.1212/01.wnl.0000247740.47667.03] [PMID: 17082464]
[http://dx.doi.org/10.1016/j.neurol.2015.09.012] [PMID: 26718594]
[http://dx.doi.org/10.1002/mds.25945] [PMID: 24976103]
[http://dx.doi.org/10.1136/jnnp-2015-312283] [PMID: 26701996]
[http://dx.doi.org/10.1212/WNL.45.3.565] [PMID: 7898719]
[http://dx.doi.org/10.1016/j.ensci.2016.02.001] [PMID: 29430533]
[http://dx.doi.org/10.1016/B978-0-12-381328-2.00002-X] [PMID: 21907082]
[http://dx.doi.org/10.1038/s41582-018-0128-2] [PMID: 30683913]
[http://dx.doi.org/10.3389/fnbeh.2013.00175] [PMID: 24324416]
[http://dx.doi.org/10.1016/S0166-4328(01)00309-6] [PMID: 11682102]
[http://dx.doi.org/10.1016/j.neuroscience.2011.10.057] [PMID: 22108613]
[http://dx.doi.org/10.1016/j.scr.2016.08.013] [PMID: 27622596]
[http://dx.doi.org/10.1155/2015/381281] [PMID: 25960916]
[http://dx.doi.org/10.1016/j.gde.2017.02.011] [PMID: 28242493]
[http://dx.doi.org/10.1001/jama.1987.03400140053013] [PMID: 3656595]
[http://dx.doi.org/10.1056/NEJM199211263272201] [PMID: 1435880]
[http://dx.doi.org/10.1056/NEJM199211263272202] [PMID: 1435881]
[http://dx.doi.org/10.1056/NEJM199504273321702] [PMID: 7700284]
[http://dx.doi.org/10.1038/16060] [PMID: 10570493]
[http://dx.doi.org/10.1002/0470091452.ch14]
[http://dx.doi.org/10.1038/292154a0] [PMID: 7242681]
[http://dx.doi.org/10.1073/pnas.78.12.7634] [PMID: 6950406]
[http://dx.doi.org/10.1073/pnas.92.17.7844] [PMID: 7544005]
[http://dx.doi.org/10.1095/biolreprod55.2.254] [PMID: 8828827]
[http://dx.doi.org/10.1126/science.282.5391.1145] [PMID: 9804556]
[http://dx.doi.org/10.1006/bbrc.1996.0957] [PMID: 8687458]
[http://dx.doi.org/10.1006/dbio.1995.1085] [PMID: 7729574]
[http://dx.doi.org/10.1006/exnr.1997.6674] [PMID: 9454612]
[http://dx.doi.org/10.1073/pnas.022438099] [PMID: 11782534]
[http://dx.doi.org/10.1038/35053516] [PMID: 11253000]
[http://dx.doi.org/10.1038/76536] [PMID: 10835609]
[http://dx.doi.org/10.1046/j.1460-9568.2002.02255.x] [PMID: 12453046]
[http://dx.doi.org/10.1038/nature00900] [PMID: 12077607]
[http://dx.doi.org/10.1172/JCI21137] [PMID: 15630449]
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[http://dx.doi.org/10.1073/pnas.0801677105] [PMID: 18391196]
[http://dx.doi.org/10.1016/j.mcn.2010.06.017] [PMID: 20603216]
[http://dx.doi.org/10.1016/j.celrep.2013.02.016] [PMID: 23499447]
[http://dx.doi.org/10.1038/celldisc.2015.12] [PMID: 27462412]
[http://dx.doi.org/10.1016/j.stem.2015.01.018] [PMID: 25732245]
[http://dx.doi.org/10.1016/j.cell.2009.02.013] [PMID: 19269371]
[http://dx.doi.org/10.1111/j.1365-2184.1970.tb00347.x] [PMID: 5523063]
[http://dx.doi.org/10.1002/term.2052] [PMID: 26118731]
[http://dx.doi.org/10.1080/14653240600855905] [PMID: 16923606]
[http://dx.doi.org/10.1073/pnas.95.7.3908] [PMID: 9520466]
[http://dx.doi.org/10.1172/JCI200420935] [PMID: 15199405]
[http://dx.doi.org/10.3727/096368909X479839] [PMID: 19906332]
[http://dx.doi.org/10.1016/j.brainres.2009.11.041] [PMID: 19945443]
[http://dx.doi.org/10.1002/jnr.23879] [PMID: 27617772]
[http://dx.doi.org/10.1111/j.1471-4159.2008.05589.x] [PMID: 18665911]
[http://dx.doi.org/10.1016/j.neulet.2005.10.097] [PMID: 16359791]
[http://dx.doi.org/10.1080/19336918.2016.1139287] [PMID: 26745021]
[http://dx.doi.org/10.1073/pnas.240309797] [PMID: 11087820]
[http://dx.doi.org/10.1016/j.joen.2010.05.006] [PMID: 20728718]
[http://dx.doi.org/10.1155/2012/103503] [PMID: 23093977]
[http://dx.doi.org/10.1007/s00418-011-0858-3] [PMID: 21879347]
[http://dx.doi.org/10.1002/stem.2398] [PMID: 27273755]
[http://dx.doi.org/10.2174/1566523218666180913152615] [PMID: 30209999]
[http://dx.doi.org/10.1016/0003-9969(94)90137-6] [PMID: 7945020]
[PMID: 22133879]
[http://dx.doi.org/10.1155/2014/987678] [PMID: 24741639]
[http://dx.doi.org/10.1159/000338654] [PMID: 22739146]
[http://dx.doi.org/10.1007/s00418-009-0646-5] [PMID: 19816704]
[http://dx.doi.org/10.1634/stemcells.2007-0979] [PMID: 18499892]
[http://dx.doi.org/10.1111/odi.12119] [PMID: 23651465]
[http://dx.doi.org/10.1089/scd.2014.0117] [PMID: 25203005]
[http://dx.doi.org/10.1016/j.neuint.2009.03.017] [PMID: 19576521]
[http://dx.doi.org/10.1016/j.archoralbio.2019.03.024] [PMID: 30954806]
[http://dx.doi.org/10.1089/ten.teb.2015.0488] [PMID: 26757369]
[http://dx.doi.org/10.3892/br.2018.1108] [PMID: 29963307]
[http://dx.doi.org/10.1007/s12015-018-9854-5]
[http://dx.doi.org/10.1089/scd.2009.0258] [PMID: 20131979]
[http://dx.doi.org/10.1038/s41598-017-11028-z] [PMID: 28871128]
[http://dx.doi.org/10.1002/term.2401] [PMID: 28079995]
[http://dx.doi.org/10.1111/iej.12545] [PMID: 26354006]
[http://dx.doi.org/10.1080/19768354.2019.1626280] [PMID: 31489249]
[http://dx.doi.org/10.1186/scrt419] [PMID: 24572146]
[http://dx.doi.org/10.1016/j.joen.2016.04.004] [PMID: 27178251]
[http://dx.doi.org/10.1002/term.2249] [PMID: 28052540]
[http://dx.doi.org/10.1016/j.joen.2017.06.001] [PMID: 28781091]
[http://dx.doi.org/10.1159/000099617] [PMID: 17409736]
[http://dx.doi.org/10.1016/j.jcma.2014.08.009] [PMID: 25441769]
[http://dx.doi.org/10.1002/term.2615] [PMID: 29139614]
[http://dx.doi.org/10.1177/0022034510366846] [PMID: 20554890]
[http://dx.doi.org/10.2220/biomedres.38.135] [PMID: 28442664]
[http://dx.doi.org/10.1371/journal.pone.0075682] [PMID: 24098394]
[http://dx.doi.org/10.1007/s12035-016-0011-3] [PMID: 27422132]
[http://dx.doi.org/10.4103/1673-5374.130089] [PMID: 25206857]
[http://dx.doi.org/10.1016/j.mad.2007.12.002] [PMID: 18241911]
[http://dx.doi.org/10.1016/S8756-3282(01)00612-3] [PMID: 11728923]
[http://dx.doi.org/10.1634/stemcells.2008-0285] [PMID: 18687995]
[http://dx.doi.org/10.1016/j.jcyt.2015.12.002] [PMID: 26897559]
[http://dx.doi.org/10.1167/iovs.13-13045] [PMID: 24150755]
[http://dx.doi.org/10.1371/journal.pone.0109305] [PMID: 25290916]
[http://dx.doi.org/10.1016/j.biomaterials.2012.10.045] [PMID: 23245334]
[http://dx.doi.org/10.1089/scd.2018.0119] [PMID: 30234437]
[http://dx.doi.org/10.1155/2016/8102478] [PMID: 27403169]
[http://dx.doi.org/10.1111/j.0953-816X.2004.03314.x] [PMID: 15128393]
[http://dx.doi.org/10.1007/s00702-008-0135-3] [PMID: 18972063]
[http://dx.doi.org/10.1016/j.brainres.2010.09.042] [PMID: 20854799]
[http://dx.doi.org/10.1097/01.tp.0000173794.72151.88] [PMID: 16210973]
[http://dx.doi.org/10.1002/iub.1655] [PMID: 28685937]
[http://dx.doi.org/10.1016/j.jcyt.2018.02.371] [PMID: 29576501]
[http://dx.doi.org/10.1111/eci.12753] [PMID: 28369799]
[http://dx.doi.org/10.1016/j.brainres.2015.04.001] [PMID: 25863132]
[http://dx.doi.org/10.4103/1673-5374.165305] [PMID: 26692841]
[http://dx.doi.org/10.5966/sctm.2015-0078] [PMID: 26339036]
[http://dx.doi.org/10.1007/s12035-013-8544-1] [PMID: 23999871]
[PMID: 29366415]
[http://dx.doi.org/10.1016/j.jcyt.2014.07.013] [PMID: 25981557]
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[http://dx.doi.org/10.3390/ijms19030720] [PMID: 29498713]
[http://dx.doi.org/10.1172/JCI62516] [PMID: 23202734]
[http://dx.doi.org/10.1002/ar.24301] [PMID: 31642188]
[http://dx.doi.org/10.13005/bpj/1146]
[http://dx.doi.org/10.1016/j.bbrc.2007.04.046] [PMID: 17466951]
[http://dx.doi.org/10.1016/j.yexcr.2009.08.006] [PMID: 19686736]
[http://dx.doi.org/10.1097/WNR.0b013e3282010aff] [PMID: 17589309]
[http://dx.doi.org/10.1371/journal.pone.0019025] [PMID: 21625433]
[http://dx.doi.org/10.1186/s12929-014-0083-1] [PMID: 25248378]
[http://dx.doi.org/10.1007/s12015-014-9551-y] [PMID: 25120226]
[http://dx.doi.org/10.1016/j.brainres.2006.05.109] [PMID: 16828720]
[http://dx.doi.org/10.1007/s00018-010-0497-1] [PMID: 20725762]
[http://dx.doi.org/10.1089/scd.2008.0080] [PMID: 18554089]
[http://dx.doi.org/10.1007/978-1-60761-999-4_22]
[http://dx.doi.org/10.1634/stemcells.2007-0212] [PMID: 17656644]
[http://dx.doi.org/10.1073/pnas.0408239102] [PMID: 15778294]
[http://dx.doi.org/10.1097/WNR.0b013e3283469615] [PMID: 21532392]
[http://dx.doi.org/10.2217/rme.15.17] [PMID: 26022763]
[http://dx.doi.org/10.1007/s10571-012-9850-2] [PMID: 22569742]
[http://dx.doi.org/10.3346/jkms.2016.31.2.171] [PMID: 26839468]
[http://dx.doi.org/10.1634/stemcells.2005-0053] [PMID: 16099997]