Skip to main content

Advertisement

Log in

Current Perspective of Stem Cell Therapy in Neurodegenerative and Metabolic Diseases

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Neurodegenerative diseases have been an unsolved riddle for quite a while; to date, there are no proper and effective curative treatments and only palliative and symptomatic treatments are available to treat these illnesses. The absence of therapeutic treatments for neurodegenerative ailments has huge economic hit and strain on the society. Pharmacotherapies and various surgical procedures like deep brain stimulation are being given to the patient, but they are only effective for the symptoms and not for the diseases. This paper reviews the recent studies and development of stem cell therapy for neurodegenerative disorders. Stem cell-based treatment is a promising new way to deal with neurodegenerative diseases. Stem cell transplantation can advance useful recuperation by delivering trophic elements that impel survival and recovery of host neurons in animal models and patients with neurodegenerative maladies. Several mechanisms, for example, substitution of lost cells, cell combination, release of neurotrophic factor, proliferation of endogenous stem cell, and transdifferentiation, may clarify positive remedial results. With the current advancements in the stem cell therapies, a new hope for the cure has come out since they have potential to be a cure for the same. This review compiles stem cell therapy recent conceptions in neurodegenerative and neurometabolic diseases and updates in this field.

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

Access this article

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
Fig. 8

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

ARSA:

Arylsulfatase

BDNF:

Brain-derived neurotrophic factor

CAA:

Cerebral amyloid angiopathy

CNS:

Central nervous system

CTX:

Cerebrotendinous xanthomatosis

DA:

Dopaminergic

ESCs:

Embryonic stem cells

GDNF:

Glial cell line-derived neurotrophic factor

GFP:

Green fluorescent protein

HD:

Huntington’s disease

HTT:

Huntingtin gene

iPSCs:

Induced pluripotent stem cells

MLD:

Metachromatic leukodystrophy

MNDs:

Motor neuron diseases

MNs:

Motor neurons

MRI:

Magnetic resonance imaging

MSCs:

Mesenchymal stem cells

NCL:

Neuronal ceroid lipofuscinoses

ND:

Neurodegenerative disease

NGF:

Nerve growth factor

NPCs:

Neural progenitor cells

NSCs:

Neural stem cells

PD:

Parkinson’s disease

PET:

Positron emission tomography

PLS:

Primary lateral sclerosis

PNS:

Peripheral nervous system

SCA:

Spinocerebellar ataxia

SCs:

Stem cells

SCF:

Stem cell factor

SCTs:

Stem cell therapies

SMA:

Spinal muscular atrophy

SPECT:

Single-photon emission computed tomography

SVZ:

Subventricular zone

TSD:

Tay-Sachs disease

References

  1. Hung C-W, Chen Y-C, Hsieh W-L, Chiou S-H, Kao C-L (2010) Ageing and neurodegenerative diseases. Ageing Res Rev 9:S36–S46

    Article  PubMed  Google Scholar 

  2. Lescaudron L, Naveilhan P, Neveu I (2012) The use of stem cells in regenerative medicine for Parkinson’s and Huntington’s diseases. Curr Med Chem 19(35):6018–6035

    CAS  PubMed  Google Scholar 

  3. Lindvall O, Kokaia Z (2006) Stem cells for the treatment of neurological disorders. Nature 441(7097):1094–1096. doi:10.1038/nature04960

    Article  CAS  PubMed  Google Scholar 

  4. Vishwakarma SK, Bardia A, Tiwari SK, Paspala SAB, Khan AA (2014) Current concept in neural regeneration research: NSCs isolation, characterization and transplantation in various neurodegenerative diseases and stroke: a review. J Adv Res 5(3):277–294. doi:10.1016/j.jare.2013.04.005

    Article  PubMed  Google Scholar 

  5. Adachi N, Numakawa T, Richards M, Nakajima S, Kunugi H (2014) New insight in expression, transport, and secretion of brain-derived neurotrophic factor: implications in brain-related diseases. World journal of biological chemistry 5(4):409

    Article  PubMed  PubMed Central  Google Scholar 

  6. Young-Pearse TL, Bai J, Chang R, Zheng JB, LoTurco JJ, Selkoe DJ (2007) A critical function for β-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci 27(52):14459–14469

    Article  CAS  PubMed  Google Scholar 

  7. Gu G, Zhang W, Li M, Ni J, Wang P (2015) Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice. Neuroscience 291:81–92

    Article  CAS  PubMed  Google Scholar 

  8. Shin JW, Lee JK, Lee JE, Min WK, Schuchman EH, Jin HK, Bae JS (2011) Combined effects of hematopoietic progenitor cell mobilization from bone marrow by granulocyte colony stimulating factor and AMD3100 and chemotaxis into the brain using stromal cell-derived factor-1α in an Alzheimer’s disease mouse model. Stem Cells 29(7):1075–1089

    Article  CAS  PubMed  Google Scholar 

  9. Singh C, Liu L, Wang JM, Irwin RW, Yao J, Chen S, Henry S, Thompson RF et al (2012) Allopregnanolone restores hippocampal-dependent learning and memory and neural progenitor survival in aging 3xTgAD and nonTg mice. Neurobiol Aging 33(8):1493–1506

    Article  CAS  PubMed  Google Scholar 

  10. Bae J-S, Jin HK, Lee JK, Richardson JC, Carter JE (2013) Bone marrow-derived mesenchymal stem cells contribute to the reduction of amyloid-β deposits and the improvement of synaptic transmission in a mouse model of pre-dementia Alzheimer’s disease. Curr Alzheimer Res 10(5):524–531

    Article  CAS  PubMed  Google Scholar 

  11. Yang H, Xie Z, Wei L, Yang H, Yang S, Zhu Z, Wang P, Zhao C et al (2013) Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model. Stem Cell Res Ther 4(4):76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xue S, Chen C, Dong W, Hui G, Liu T, Guo L (2012) Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes. Science China Life Sciences 55(2):132–140

    Article  CAS  PubMed  Google Scholar 

  13. Olson L (1993) NGF and the treatment of Alzheimer’s disease. Exp Neurol 124(1):5–15

    Article  CAS  PubMed  Google Scholar 

  14. Tuszynski MH, Yang JH, Barba D, Hoi-Sang U, Bakay RA, Pay MM, Masliah E, Conner JM et al (2015) Nerve growth factor Gene therapy: activation of neuronal responses in Alzheimer disease. JAMA neurology 72(10):1139–1147

    Article  PubMed  PubMed Central  Google Scholar 

  15. Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278(5337):412–419

    Article  CAS  PubMed  Google Scholar 

  16. Perry E, Walker M, Grace J, Perry R (1999) Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci 22(6):273–280

    Article  CAS  PubMed  Google Scholar 

  17. Fisher A (2008) Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer’s disease. Neurotherapeutics 5(3):433–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mochizuki H, Goto K, Mori H, Mizuno Y (1996) Histochemical detection of apoptosis in Parkinson’s disease. J Neurol Sci 137(2):120–123

    Article  CAS  PubMed  Google Scholar 

  20. Tatton NA (2000) Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson’s disease. Exp Neurol 166(1):29–43

    Article  CAS  PubMed  Google Scholar 

  21. Perju-Dumbrava LD, Kovacs GG, Pirker S, Jellinger K, Hoffmann M, Asenbaum S, Pirker W (2012) Dopamine transporter imaging in autopsy-confirmed Parkinson’s disease and multiple system atrophy. Mov Disord 27(1):65–71

    Article  PubMed  Google Scholar 

  22. Pranzatelli MR, Mott SH, Pavlakis SG, Conry JA, Tate ED (1994) Clinical spectrum of secondary parkinsonism in childhood: a reversible disorder. Pediatr Neurol 10(2):131–140

    Article  CAS  PubMed  Google Scholar 

  23. Simon-Sanchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P et al (2009) Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet 41(12):1308–1312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Consortium IPDG (2011) Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet 377(9766):641–649

    Article  CAS  Google Scholar 

  25. Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R, Leenders KL, Sawle G et al (1990) Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 247(4942):574–577

    Article  CAS  PubMed  Google Scholar 

  26. Hagell P, Schrag A, Piccini P, Jahanshahi M, Brown R, Rehncrona S, Widner H, Brundin P et al (1999) Sequential bilateral transplantation in Parkinson’s disease. Brain 122(6):1121–1132

    Article  PubMed  Google Scholar 

  27. Altman J, Das GD (1965) Post-natal origin of microneurones in the rat brain. Nature 207(5000):953

    Article  CAS  PubMed  Google Scholar 

  28. Nishino H, Hida H, Takei N, Kumazaki M, Nakajima K, Baba H (2000) Mesencephalic neural stem (progenitor) cells develop to dopaminergic neurons more strongly in dopamine-depleted striatum than in intact striatum. Exp Neurol 164(1):209–214

    Article  CAS  PubMed  Google Scholar 

  29. Barker RA, Barrett J, Mason SL, Björklund A (2013) Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson’s disease. The Lancet Neurology 12(1):84–91

    Article  CAS  PubMed  Google Scholar 

  30. Kefalopoulou Z, Politis M, Piccini P, Mencacci N, Bhatia K, Jahanshahi M, Widner H, Rehncrona S et al (2014) Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA neurology 71(1):83–87

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kawasaki H, Mizuseki K, Nishikawa S, Kaneko S, Kuwana Y, Nakanishi S, Nishikawa S-I, Sasai Y (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell–derived inducing activity. Neuron 28(1):31–40

    Article  CAS  PubMed  Google Scholar 

  32. O’Keeffe FE, Scott SA, Tyers P, O’Keeffe GW, Dalley JW, Zufferey R, Caldwell MA (2008) Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson’s disease. Brain 131(3):630–641

    Article  PubMed  Google Scholar 

  33. Kim J-H, Auerbach JM, Rodríguez-Gómez JA, Velasco I, Gavin D, Lumelsky N, Lee S-H, Nguyen J et al (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418(6893):50–56

    Article  CAS  PubMed  Google Scholar 

  34. Grealish S, Diguet E, Kirkeby A, Mattsson B, Heuer A, Bramoulle Y, Van Camp N, Perrier AL et al (2014) Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease. Cell Stem Cell 15(5):653–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Muramatsu SI, Okuno T, Suzuki Y, Nakayama T, Kakiuchi T, Takino N, Iida A, Ono F et al (2009) Multitracer assessment of dopamine function after transplantation of embryonic stem cell-derived neural stem cells in a primate model of Parkinson’s disease. Synapse 63(7):541–548

    Article  CAS  PubMed  Google Scholar 

  36. Wernig M, Zhao J-P, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M et al (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci 105(15):5856–5861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kim J, Su SC, Wang H, Cheng AW, Cassady JP, Lodato MA, Lengner CJ, Chung C-Y et al (2011) Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell 9(5):413–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Miller RG, Mitchell J, Lyon M, Moore DH (2007) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 1(1)

  39. Leigh PN, Ray-Chaudhuri K (1994) Motor neuron disease. J Neurol Neurosurg Psychiatry 57(8):886–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bruijn LI, Miller TM, Cleveland DW (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27:723–749

    Article  CAS  PubMed  Google Scholar 

  41. Puls I, Jonnakuty C, LaMonte BH, Holzbaur EL, Tokito M, Mann E, Floeter MK, Bidus K et al (2003) Mutant dynactin in motor neuron disease. Nat Genet 33(4):455–456

    Article  CAS  PubMed  Google Scholar 

  42. Lee MK, Marszalek JR, Cleveland DW (1994) A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron 13(4):975–988

    Article  CAS  PubMed  Google Scholar 

  43. Gitcho MA, Baloh RH, Chakraverty S, Mayo K, Norton JB, Levitch D, Hatanpaa KJ, White CL et al (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63(4):535–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Boillée S, Velde CV, Cleveland DW (2006) ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 52(1):39–59

    Article  PubMed  CAS  Google Scholar 

  45. Machts J, Bittner V, Kasper E, Schuster C, Prudlo J, Abdulla S, Kollewe K, Petri S et al (2014) Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment. BMC Neurosci 15(1):83

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Lomen-Hoerth C, Murphy J, Langmore S, Kramer J, Olney R, Miller B (2003) Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60(7):1094–1097

    Article  CAS  PubMed  Google Scholar 

  47. Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344(22):1688–1700. doi:10.1056/NEJM200105313442207

    Article  CAS  PubMed  Google Scholar 

  48. Karam C, Scelsa SN, MacGowan DJ (2010) The clinical course of progressive bulbar palsy. Amyotroph Lateral Scler 11(4):364–368

    Article  PubMed  Google Scholar 

  49. Gordon P, Cheng B, Katz I, Pinto M, Hays A, Mitsumoto H, Rowland L (2006) The natural history of primary lateral sclerosis. Neurology 66(5):647–653

    Article  CAS  PubMed  Google Scholar 

  50. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80(1):155–165

    Article  CAS  PubMed  Google Scholar 

  51. Fan L, Simard LR (2002) Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development. Hum Mol Genet 11(14):1605–1614

    Article  CAS  PubMed  Google Scholar 

  52. Brzustowicz LM, Lehner T, Castilla LH, Penchaszadeh GK, Wilhelmsen KC, Daniels R, Davies KE, Leppert M et al (1990) Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3. Nature 344(6266):540–541. doi:10.1038/344540a0

    Article  CAS  PubMed  Google Scholar 

  53. Shetty P, Pradhan S, Viswanathan C (2015) A highly efficient culture technique for derivation of motor neurons from human umbilical cord derived mesenchymal stem cells. Journal of Neurology and Neurological Disorders 1(2):1

    Google Scholar 

  54. Park H-W, Cho J-S, Park C-K, Jung SJ, Park C-H, Lee S-J, Oh SB, Park Y-S et al (2012) Directed induction of functional motor neuron-like cells from genetically engineered human mesenchymal stem cells. PLoS One 7(4):e35244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Marconi S, Bonaconsa M, Scambi I, Squintani G, Rui W, Turano E, Ungaro D, D’Agostino S et al (2013) Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model. Neuroscience 248:333–343

    Article  CAS  PubMed  Google Scholar 

  56. Fan C-G, Zhang Q-J, Zhou J-R (2011) Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev Rep 7(1):195–207

    Article  Google Scholar 

  57. Van Den Bosch L, Timmerman V (2006) Genetics of motor neuron disease. Curr Neurol Neurosci Rep :423–431

  58. Crigler L, Robey RC, Asawachaicharn A, Gaupp D, Phinney DG (2006) Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp Neurol 198(1):54–64

    Article  CAS  PubMed  Google Scholar 

  59. Sun H, Benardais K, Stanslowsky N, Thau-Habermann N, Hensel N, Huang D, Claus P, Dengler R et al (2013) Therapeutic potential of mesenchymal stromal cells and MSC conditioned medium in Amyotrophic Lateral Sclerosis (ALS)—in vitro evidence from primary motor neuron cultures, NSC-34 cells, astrocytes and microglia. PloS one 8(9):e72926. doi:10.1371/journal.pone.0072926

  60. Clelland CD, Barker RA, Watts C (2008) Cell therapy in Huntington disease. Neurosurg Focus 24(3–4):E9

    Article  PubMed  Google Scholar 

  61. Martin JB, Gusella JF (1986) Huntingtons disease. N Engl J Med 315(20):1267–1276. doi:10.1056/NEJM198611133152006

    Article  CAS  PubMed  Google Scholar 

  62. Gutekunst C-A, Norflus F, Hersch S (2002) The neuropathology of Huntington’s disease. OXFORD MONOGRAPHS ON MEDICAL GENETICS 45(1):251–275

    Google Scholar 

  63. Rubinsztein D (2003) Molecular biology of Huntington’s disease (HD) and HD-like disorders. Genet Mov Disord (Pulst, S, Ed) :365–377

  64. Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57(5):369–384

    Article  CAS  PubMed  Google Scholar 

  65. MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, Barnes G, Taylor SA et al (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72(6):971–983

    Article  Google Scholar 

  66. Vonsattel JPG (2008) Huntington disease models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):55–69

    Article  PubMed  Google Scholar 

  67. Group HS (2006) Tetrabenazine as antichorea therapy in Huntington disease a randomized controlled trial. Neurology 66(3):366–372

    Article  CAS  Google Scholar 

  68. Djousse L, Knowlton B, Cupples L, Marder K, Shoulson I, Myers R (2002) Weight loss in early stage of Huntington’s disease. Neurology 59(9):1325–1330

    Article  CAS  PubMed  Google Scholar 

  69. Dunnett SB, Rosser AE (2014) Challenges for taking primary and stem cells into clinical neurotransplantation trials for neurodegenerative disease. Neurobiol Dis 61:79–89

    Article  PubMed  Google Scholar 

  70. Bachoud-Lévi A-C, Rémy P, Nǵuyen J-P, Brugières P, Lefaucheur J-P, Bourdet C, Baudic S, Gaura V et al (2000) Motor and cognitive improvements in patients with Huntington’s disease after neural transplantation. Lancet 356(9246):1975–1979

    Article  PubMed  Google Scholar 

  71. Keene CD, Chang RC, Leverenz JB, Kopyov O, Perlman S, Hevner RF, Born DE, Bird TD et al (2009) A patient with Huntington’s disease and long-surviving fetal neural transplants that developed mass lesions. Acta Neuropathol 117(3):329–338

    Article  PubMed  Google Scholar 

  72. McBride JL, Behrstock SP, Chen EY, Jakel RJ, Siegel I, Svendsen CN, Kordower JH (2004) Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease. J Comp Neurol 475(2):211–219

    Article  PubMed  Google Scholar 

  73. Viegas P, Nicoleau C, Perrier AL (2011) Derivation of striatal neurons from human stem cells. Prog Brain Res 200:373–404

    Article  Google Scholar 

  74. Precious SV, Rosser AE (2012) Producing striatal phenotypes for transplantation in Huntington’s disease. Exp Biol Med 237(4):343–351

    Article  CAS  Google Scholar 

  75. Carri AD, Onorati M, Lelos MJ, Castiglioni V, Faedo A, Menon R, Camnasio S, Vuono R et al (2013) Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons. Development 140(2):301–312

    Article  CAS  Google Scholar 

  76. Ma L, Hu B, Liu Y, Vermilyea SC, Liu H, Gao L, Sun Y, Zhang X et al (2012) Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice. Cell Stem Cell 10(4):455–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kelly C, Dunnett S, Rosser A (2009) Medium spiny neurons for transplantation in Huntington’s disease. Biochem Soc Trans 37(1):323

    Article  CAS  PubMed  Google Scholar 

  78. Lo B, Parham L (2010) Resolving ethical issues in stem cell clinical trials: the example of Parkinson disease. The Journal of Law, Medicine & Ethics 38(2):257–266

    Article  Google Scholar 

  79. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén J (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96(1):25–34

    Article  CAS  PubMed  Google Scholar 

  80. Bae JH, Mun KC, Park WK, Lee S-R, Suh S-I, Baek WK, Yim M-B, Kwon TK et al (2002) EGCG attenuates AMPA-induced intracellular calcium increase in hippocampal neurons. Biochem Biophys Res Commun 290(5):1506–1512

    Article  CAS  PubMed  Google Scholar 

  81. Hong S-B, Seo M-S, Park S-B, Seo Y-J, Kim J-S, Kang K-S (2012) Therapeutic effects of human amniotic epithelial stem cells in Niemann–pick type C1 mice. Cytotherapy 14(5):630–638

    Article  CAS  PubMed  Google Scholar 

  82. Park HJ, Lee PH, Bang OY, Lee G, Ahn YH (2008) Mesenchymal stem cells therapy exerts neuroprotection in a progressive animal model of Parkinson’s disease. J Neurochem 107(1):141–151

    Article  CAS  PubMed  Google Scholar 

  83. Bilney B, Morris ME, Perry A (2003) Effectiveness of physiotherapy, occupational therapy, and speech pathology for people with Huntington’s disease: a systematic review. Neurorehabil Neural Repair 17(1):12–24

    Article  PubMed  Google Scholar 

  84. Brown K, Brown J, Ritchie D, Sales J, Fraser J (2001) Fetal cell grafts provide long-term protection against scrapie induced neuronal loss. Neuroreport 12(1):77–82

    Article  CAS  PubMed  Google Scholar 

  85. Allers C, Jones JA, Lasala GP, Minguell JJ (2014) Mesenchymal stem cell therapy for the treatment of amyotrophic lateral sclerosis: signals for hope? Regen Med 9(5):637–647

    Article  CAS  PubMed  Google Scholar 

  86. Jin J-L, Liu Z, Lu Z-J, Guan D-N, Wang C, Chen Z-B, Zhang J, Zhang W-Y et al (2013a) Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res 10(1):11–20

    Article  CAS  PubMed  Google Scholar 

  87. Barresi V, Belluardo N, Sipione S, Mudó G, Cattaneo E, Condorelli DF (2003) Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy. Cancer Gene Ther 10(5):396–402

    Article  CAS  PubMed  Google Scholar 

  88. Benedetti S, Pirola B, Pollo B, Magrassi L, Bruzzone MG, Rigamonti D, Galli R, Selleri S et al (2000) Gene therapy of experimental brain tumors using neural progenitor cells. Nat Med 6(4):447–450

    Article  CAS  PubMed  Google Scholar 

  89. Navarro C, Fernandez J, Dominguez C, Fachal C, Alvarez M (1996) Late juvenile metachromatic leukodystrophy treated with bone marrow transplantation a 4-year follow-up study. Neurology 46(1):254–256

    Article  CAS  PubMed  Google Scholar 

  90. Bayever E, Philippart M, Nuwer M, Ladisch S, Brill N, Sparkes R, Feig S (1985) Bone-marrow transplantation for metachromatic leucodystrophy. Lancet 326(8453):471–473

    Article  Google Scholar 

  91. Aubourg P, Blanche S, Jambaqué I, Rocchiccioli F, Kalifa G, Naud-Saudreau C, Rolland M-O, Debré M et al (1990) Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. N Engl J Med 322(26):1860–1866

    Article  CAS  PubMed  Google Scholar 

  92. Krivit W, Shapiro EG, Peters C, Wagner JE, Cornu G, Kurtzberg J, Wenger DA, Kolodny EH et al (1998a) Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med 338(16):1119–1127

    Article  CAS  PubMed  Google Scholar 

  93. Pulst S-M (2000) Neurogenetics, vol 57. Oxford University Press

  94. Moseley ML, Benzow K, Schut L, Bird TD, Gomez C, Barkhaus P, Blindauer K, Labuda M et al (1998) Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 51(6):1666–1671

    Article  CAS  PubMed  Google Scholar 

  95. Schöls L, Bauer P, Schmidt T, Schulte T, Riess O (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. The Lancet Neurology 3(5):291–304

    Article  PubMed  Google Scholar 

  96. Chang YK, Chen MH, Chiang YH, Chen YF, Ma WH, Tseng CY, Soong BW, Ho JH et al (2011) Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells. J Biomed Sci 18:54. doi:10.1186/1423-0127-18-54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Jin JL, Liu Z, Lu ZJ, Guan DN, Wang C, Chen ZB, Zhang J, Zhang WY et al (2013b) Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res 10(1):11–20

    Article  CAS  PubMed  Google Scholar 

  98. Xia G, Santostefano K, Hamazaki T, Liu J, Subramony SH, Terada N, Ashizawa T (2013) Generation of human-induced pluripotent stem cells to model spinocerebellar ataxia type 2 in vitro. Journal of molecular neuroscience : MN 51(2):237–248. doi:10.1007/s12031-012-9930-2

    Article  CAS  PubMed  Google Scholar 

  99. Matsuura S, Shuvaev AN, Iizuka A, Nakamura K, Hirai H (2014) Mesenchymal stem cells ameliorate cerebellar pathology in a mouse model of spinocerebellar ataxia type 1. Cerebellum (London, England) 13(3):323–330. doi:10.1007/s12311-013-0536-1

    Article  CAS  Google Scholar 

  100. Biffi A, Lucchini G, Rovelli A, Sessa M (2008) Metachromatic leukodystrophy: an overview of current and prospective treatments. Bone Marrow Transplant 42:S2–S6

    Article  PubMed  Google Scholar 

  101. Eckhardt M (2008) The role and metabolism of sulfatide in the nervous system. Mol Neurobiol 37(2–3):93–103

    Article  CAS  PubMed  Google Scholar 

  102. Sevin C, Aubourg P, Cartier N (2007) Enzyme, cell and gene-based therapies for metachromatic leukodystrophy. J Inherit Metab Dis 30(2):175–183

    Article  CAS  PubMed  Google Scholar 

  103. Schmahmann JD, Smith EE, Eichler FS, Filley CM (2008) Cerebral white matter. Ann N Y Acad Sci 1142(1):266–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Gieselmann V (2008) Metachromatic leukodystrophy: genetics, pathogenesis and therapeutic options. Acta Paediatr 97(s457):15–21

    Article  PubMed  Google Scholar 

  105. Kehrer C, Groeschel S, Kustermann-Kuhn B, Bürger F, Köhler W, Kohlschütter A, Bley A, Steinfeld R et al (2014) Language and cognition in children with metachromatic leukodystrophy: onset and natural course in a nationwide cohort. Orphanet journal of rare diseases 9(1):1–9

    Article  Google Scholar 

  106. Hyde TM, Ziegler JC, Weinberger DR (1992) Psychiatric disturbances in metachromatic leukodystrophy: insights into the neurobiology of psychosis. Arch Neurol 49(4):401–406

    Article  CAS  PubMed  Google Scholar 

  107. Solders M, Martin DA, Andersson C, Remberger M, Andersson T, Ringden O, Solders G (2014) Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy. Bone Marrow Transplant 49(8):1046–1051. doi:10.1038/bmt.2014.93

    Article  CAS  PubMed  Google Scholar 

  108. Martin HR, Poe MD, Provenzale JM, Kurtzberg J, Mendizabal A, Escolar ML (2013) Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 19(4):616–624. doi:10.1016/j.bbmt.2013.01.010

    Article  Google Scholar 

  109. Liu XY, Gonzalez-Toledo ME, Fagan A, Duan WM, Liu Y, Zhang S, Li B et al (2015) Stem cell factor and granulocyte colony-stimulating factor exhibit therapeutic effects in a mouse model of CADASIL. Neurobiol Dis 73:189–203. doi:10.1016/j.nbd.2014.09.006

    Article  CAS  PubMed  Google Scholar 

  110. Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80(4):844–866

    Article  CAS  PubMed  Google Scholar 

  111. Greenberg SM (1998) Cerebral amyloid angiopathy prospects for clinical diagnosis and treatment. Neurology 51(3):690–694

    Article  CAS  PubMed  Google Scholar 

  112. Cheung C, Goh YT, Zhang J, Wu C, Guccione E (2014) Modeling cerebrovascular pathophysiology in amyloid-beta metabolism using neural-crest-derived smooth muscle cells. Cell Rep 9(1):391–401. doi:10.1016/j.celrep.2014.08.065

    Article  CAS  PubMed  Google Scholar 

  113. Irle E, Markowitsch HJ (1983) Widespread neuroanatomical damage and learning deficits following chronic alcohol consumption or vitamin-B 1 (thiamine) deficiency in rats. Behav Brain Res 9(3):277–294

    Article  CAS  PubMed  Google Scholar 

  114. Maiese K, Chong ZZ (2003) Nicotinamide: necessary nutrient emerges as a novel cytoprotectant for the brain. Trends Pharmacol Sci 24(5):228–232

    Article  CAS  PubMed  Google Scholar 

  115. Schaumburg H, Kaplan J, Windebank A, Vick N, Rasmus S, Pleasure D, Brown MJ (1983) Sensory neuropathy from pyridoxine abuse: a new megavitamin syndrome. N Engl J Med 309(8):445–448

    Article  CAS  PubMed  Google Scholar 

  116. Reynolds E (2006) Vitamin B12, folic acid, and the nervous system. The Lancet Neurology 5(11):949–960

    Article  CAS  PubMed  Google Scholar 

  117. Delange F (2001) Iodine deficiency as a cause of brain damage. Postgrad Med J 77(906):217–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5(11):863–873

    Article  CAS  PubMed  Google Scholar 

  119. Assaf S, Chung S-H (1984) Release of endogenous Zn2+ from brain tissue during activity

  120. Bourre J-M (2006) Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. Journal of Nutrition Health and Aging 10(5):377

    CAS  Google Scholar 

  121. Burn D, Bates D (1998) Neurology and the kidney. J Neurol Neurosurg Psychiatry 65(6):810–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. De Onis M, Monteiro C, Akré J, Clugston G (1993) The worldwide magnitude of protein-energy malnutrition: an overview from the WHO global database on child growth. Bull World Health Organ 71(6):703–712

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Blansjaar BA, Vielvoye GJ, Van Dijk JG, Rijnders RJ (1992) Similar brain lesions in alcoholics and Korsakoff patients: MRI, psychometric and clinical findings. Clin Neurol Neurosurg 94(3):197–203

    Article  CAS  PubMed  Google Scholar 

  124. Harper C (1998) The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? J Neuropathol Exp Neurol 57(2):101–110

    Article  CAS  PubMed  Google Scholar 

  125. Malouf R, Areosa Sastre A (2003) Vitamin B12 for cognition. Cochrane Database Syst Rev 3(3)

  126. Thaver D, Saeed MA, Bhutta ZA (2006) Pyridoxine (vitamin B6) supplementation in pregnancy. The Cochrane Library

  127. Lumley J, Watson L, Watson M, Bower C (2002) Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects (Review). Cochrane Database Syst Rev (2)

  128. Dong H, Wade M, Williams A, Lee A, Douglas GR, Yauk C (2005) Molecular insight into the effects of hypothyroidism on the developing cerebellum. Biochem Biophys Res Commun 330(4):1182–1193

    Article  CAS  PubMed  Google Scholar 

  129. Lasley S, Gilbert M (2011) Developmental thyroid hormone insufficiency reduces expression of brain-derived neurotrophic factor (BDNF) in adults but not in neonates. Neurotoxicol Teratol 33(4):464–472

    Article  CAS  PubMed  Google Scholar 

  130. Shirabe T, Tawara S, Terao A, Araki S (1975) Myxoedematous polyneuropathy: a light and electron microscopic study of the peripheral nerve and muscle. J Neurol Neurosurg Psychiatry 38(3):241–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Martin J, Tomkin G, Hutchinson M (1983) Peripheral neuropathy in hypothyroidism—an association with spurious Polycythaemia (Gaisbock’s syndrome). J R Soc Med 76(3):187–189

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Dezonne RS, Stipursky J, Gomes FCA (2009) Effect of thyroid hormone depletion on cultured murine cerebral cortex astrocytes. Neurosci Lett 467(2):58–62

    Article  CAS  PubMed  Google Scholar 

  133. Ritchie M, Yeap BB (2015) Thyroid hormone: influences on mood and cognition in adults. Maturitas 81(2):266–275

    Article  CAS  PubMed  Google Scholar 

  134. Wang Y, Sheng Q, Hou X, Wang B, Zhao W, Yan S, Wang Y, Zhao S (2015) Thyrotropin and Alzheimer’s disease risk in the elderly: a systematic review and meta-analysis. Mol Neurobiol :1–8

  135. Joffe RT, Gatt JM, Kemp AH, Grieve S, Dobson-Stone C, Kuan SA, Schofield PR, Gordon E et al (2009) Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: implications for depressive illness. Hum Brain Mapp 30(4):1246–1256

    Article  PubMed  Google Scholar 

  136. Nordqvist P (1960) Myxoedema coma and CO2-retention. Acta Medica Scandinavica :189–194

  137. Dutta P, Bhansali A, Masoodi SR, Bhadada S, Sharma N, Rajput R (2008) Predictors of outcome in myxoedema coma: a study from a tertiary care Centre. Crit Care 12(1):R1

    Article  PubMed  PubMed Central  Google Scholar 

  138. Hultberg B (1969) N-Acetylhexosaminidase activities in Tay-Sachs disease. Lancet 294(7631):1195

    Article  Google Scholar 

  139. Barnes D, Misra V, Young E, Thomas P, Harding A (1991) An adult onset hexosaminidase a deficiency syndrome with sensory neuropathy and internuclear ophthalmoplegia. J Neurol Neurosurg Psychiatry 54(12):1112–1113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Bolhuis P, Oonk J, Kamp P, Ris A, Michalski J, Overdijk B, Reuser A (1987) Ganglioside storage, hexosarninidase lability, and urinary oligosaccharides in adult Sandhoff’s disease. Neurology 37(1):75–75

    Article  CAS  PubMed  Google Scholar 

  141. Cox T (2001) Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. J Inherit Metab Dis 24(2):107–123

    Article  Google Scholar 

  142. Andrews JM, Cancilla PA, Grippo J, Menkes JH (1971) Globoid cell leukodystrophy (Krabbe’s disease): morphological and biochemical studies. Neurology 21(4):337–352

    Article  CAS  PubMed  Google Scholar 

  143. Krivit W, Shapiro EG, Peters C, Wagner JE, Cornu G, Kurtzberg J, Wenger DA, Kolodny EH et al (1998b) Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med 338(16):1119–1126. doi:10.1056/nejm199804163381605

    Article  CAS  PubMed  Google Scholar 

  144. Coker SB (1991) The diagnosis of childhood neurodegenerative disorders presenting as dementia in adults. Neurol

    Google Scholar 

  145. Berginer VM, Salen G, Shefer S (1984) Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med 311(26):1649–1652

    Article  CAS  PubMed  Google Scholar 

  146. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, Margell PD, Stabler SP et al (1988) Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 318(26):1720–1728

    Article  CAS  PubMed  Google Scholar 

  147. Desai V, Kaler SG (2008) Role of copper in human neurological disorders. Am J Clin Nutr 88(3):855S–858S

    CAS  PubMed  Google Scholar 

  148. Heine W (2004) Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves. Exp Neurol 231–240.

  149. Dispenzieri A, Moreno-Aspitia A, Suarez GA, Lacy MQ, Colon-Otero G, Tefferi A, Litzow MR, Roy V et al (2004) Peripheral blood stem cell transplantation in 16 patients with POEMS syndrome, and a review of the literature. Blood 104(10):3400–3407

    Article  CAS  PubMed  Google Scholar 

  150. Jaccard A, Royer B, Bordessoule D, Brouet J-C, Fermand J-P (2002) High-dose therapy and autologous blood stem cell transplantation in POEMS syndrome. Blood 99(8):3057–3059

    Article  CAS  PubMed  Google Scholar 

  151. Kuwabara S, Misawa S, Kanai K, Suzuki Y, Kikkawa Y, Sawai S, Hattori T, Nishimura M et al (2008) Neurologic improvement after peripheral blood stem cell transplantation in POEMS syndrome. Neurology 71(21):1691–1695

    Article  CAS  PubMed  Google Scholar 

  152. De Coppi P, Bartsch G, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC et al (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25(1):100–106

    Article  CAS  PubMed  Google Scholar 

  153. Krivit W (2004) Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer seminars in immunopathology. Springer, In, pp. 119–132

    Google Scholar 

  154. Aldenhoven M, Kurtzberg J (2015) Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions. Cytotherapy 17(6):765–774

    Article  CAS  PubMed  Google Scholar 

  155. Rodriguez-Porcel MWJ, Gambhir SS (2009) Molecular imaging of stem cells. StemBook. doi:10.3824/stembook.1.49.1

    Google Scholar 

  156. Tong L, Zhao H, He Z, Li Z (2013) Current perspectives on molecular imaging for tracking stem cell therapy. Med Imaging Clin Pract. doi:40177

  157. Ngen EJ, Wang L, Kato Y, Krishnamachary B, Zhu W, Gandhi N, Smith B, Armour M et al (2015) Imaging transplanted stem cells in real time using an MRI dual-contrast method. Scientific reports 5:13628. doi:10.1038/srep13628

    Article  PubMed  PubMed Central  Google Scholar 

  158. Guzman R, Uchida N, Bliss TM, He D, Christopherson KK, Stellwagen D, Capela A, Greve J et al (2007) Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci 104(24):10211–10216. doi:10.1073/pnas.0608519104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Legacz M, Roepke K, Giersig M, Pison U (2014) Contrast agents and cell labeling strategies for in vivo imaging. Adv Nanoparticles 2014

  160. Björklund LM, Sánchez-Pernaute R, Chung S, Andersson T, Chen IYC, McNaught KSP, Brownell A-L, Jenkins BG et al (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci 99(4):2344–2349. doi:10.1073/pnas.022438099

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Iordanova B, Ahrens ET (2012) In vivo magnetic resonance imaging of ferritin-based reporter visualizes native neuroblast migration. NeuroImage 59(2):1004–1012. doi:10.1016/j.neuroimage.2011.08.068

    Article  CAS  PubMed  Google Scholar 

  162. Daadi MM, Hu S, Klausner J, Li Z, Sofilos M, Sun G, Wu JC, Steinberg GK (2013) Imaging neural stem cell graft-induced structural repair in stroke. Cell Transplant 22(5):881–892. doi:10.3727/096368912x656144

    Article  PubMed  Google Scholar 

  163. Gao Y, Cui Y, Chan JKY, Xu C (2013) Stem cell tracking with optically active nanoparticles. American Journal of Nuclear Medicine and Molecular Imaging 3(3):232–246

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Li L, Jiang W, Luo K, Song H, Lan F, Wu Y, Gu Z (2013) Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking. Theranostics 3(8):595–615. doi:10.7150/thno.5366

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Kim MH, Woo S-K, Kim KI, Lee TS, Kim CW, Kang JH, Kim BI, Lim SM et al (2015) Simple methods for tracking stem cells with (64)Cu-labeled DOTA-hexadecyl-benzoate. ACS Med Chem Lett 6(5):528–530. doi:10.1021/acsmedchemlett.5b00021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Xu C, Mu L, Roes I, Miranda-Nieves D, Nahrendorf M, Ankrum JA, Zhao W, Karp JM (2011) Nanoparticle-based monitoring of cell therapy. Nanotechnology 22(49):494001–494001. doi:10.1088/0957-4484/22/49/494001

    Article  PubMed  PubMed Central  Google Scholar 

  167. Liu C, Yu Y, Miao L, Liu Y, Sun W (2016) A comparative study of transfection of rat mesenchymal stem cells using polyethyleneimine-coated magnetic ferro-ferric oxide nanoparticles and lipofectamine. Int J Clin Exp Med 9(3):6062–6069

    Google Scholar 

  168. Dehdilani N, Shamsasenjan K, Movassaghpour A, Akbarzadehlaleh P, Amoughli Tabrizi B, Parsa H, Sabagi F (2016) Improved survival and hematopoietic differentiation of murine embryonic stem cells on electrospun Polycaprolactone nanofiber. Cell journal 17(4):629–638

    PubMed  PubMed Central  Google Scholar 

  169. Andersen MO, Nygaard JV, Burns JS, Raarup MK, Nyengaard JR, Bunger C, Besenbacher F, Howard KA et al (2010) siRNA nanoparticle functionalization of nanostructured scaffolds enables controlled multilineage differentiation of stem cells. Mol Ther 18(11):2018–2027 http://www.nature.com/mt/journal/v18/n11/suppinfo/mt2010166s1.html

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Li H-C, Stoicov C, Rogers AB, Houghton J (2006) Stem cells and cancer: evidence for bone marrow stem cells in epithelial cancers. World Journal of Gastroenterology : WJG 12(3):363–371. doi:10.3748/wjg.v12.i3.363

    Article  PubMed  PubMed Central  Google Scholar 

  171. Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, Paz N, Koren-Michowitz M et al (2009) Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med 6(2):e1000029. doi:10.1371/journal.pmed.1000029

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  172. Shih CC, Forman SJ, Chu P, Slovak M (2007) Human embryonic stem cells are prone to generate primitive, undifferentiated tumors in engrafted human fetal tissues in severe combined immunodeficient mice. Stem Cells Dev 16(6):893–902. doi:10.1089/scd.2007.0070

    Article  CAS  PubMed  Google Scholar 

  173. Hong SG, Dunbar CE, Winkler T (2013) Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells. Mol Ther 21(2):272–281

    Article  CAS  PubMed  Google Scholar 

  174. Lazennec G, Jorgensen C (2008) Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem cells (Dayton, Ohio) 26(6):1387–1394. doi:10.1634/stemcells.2007-1006

    Article  CAS  Google Scholar 

  175. Mohib K, Allan D, Wang L (2010) Human embryonic stem cell-extracts inhibit the differentiation and function of monocyte-derived dendritic cells. Stem Cell Rev 6(4):611–621. doi:10.1007/s12015-010-9185-7

    Article  PubMed  Google Scholar 

  176. Herberts CA, Kwa MSG, Hermsen HPH (2011) Risk factors in the development of stem cell therapy. J Transl Med 9:29–29. doi:10.1186/1479-5876-9-29

    Article  PubMed  PubMed Central  Google Scholar 

  177. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147

    Article  CAS  PubMed  Google Scholar 

  178. Löser P, Schirm J, Guhr A, Wobus AM, Kurtz A (2010) Human embryonic stem cell lines and their use in international research. Stem Cells 28(2):240–246

    PubMed  PubMed Central  Google Scholar 

  179. Strelchenko N, Verlinsky O, Kukharenko V, Verlinsky Y (2004) Morula-derived human embryonic stem cells. Reprod BioMed Online 9(6):623–629

    Article  PubMed  Google Scholar 

  180. Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M (2006) Derivation of human embryonic stem cells from developing and arrested embryos. Stem Cells 24(12):2669–2676

    Article  CAS  PubMed  Google Scholar 

  181. Klimanskaya I, Chung Y, Becker S, Lu S-J, Lanza R (2007) Derivation of human embryonic stem cells from single blastomeres. Nat Protoc 2(8):1963–1972

    Article  CAS  PubMed  Google Scholar 

  182. Feki A, Hovatta O, Jaconi M (2008) Derivation of human embryonic stem cell lines from single cells of 4-cell stage embryos: be aware of the risks. Hum Reprod

  183. Geens M, Mateizel I, Sermon K, De Rycke M, Spits C, Cauffman G, Devroey P, Tournaye H et al (2009) Human embryonic stem cell lines derived from single blastomeres of two 4-cell stage embryos. Hum Reprod 24(11):2709–2717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The Authors PP and BG like to acknowledge Ministry of Education (MOE) for Startup Grant and Tier 1 Grant. KN like to acknowledge Institute of Bioengineering and Nanotechnology, Singapore for funding. KJV like to acknowledge National Dental Centre research fund, Singapore.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Karthikeyan Narayanan, Parasuraman Padmanabhan or Balázs Gulyás.

Ethics declarations

Research Involving Human Participants and/or Animals

Not applicable.

Informed Consent

Not applicable.

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Narayanan, K., Chaudhary, R.K. et al. Current Perspective of Stem Cell Therapy in Neurodegenerative and Metabolic Diseases. Mol Neurobiol 54, 7276–7296 (2017). https://doi.org/10.1007/s12035-016-0217-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-016-0217-4

Keywords

Navigation