Harnessing Stem Cells and Neurotrophic Factors with Novel Technologies in the Treatment of Parkinson’s Disease

Author(s): Massimo Conese*, Roberta Cassano, Elisabetta Gavini, Giuseppe Trapani, Giovanna Rassu, Enrico Sanna, Sante Di Gioia, Adriana Trapani.

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 7 , 2019

Become EABM
Become Reviewer


Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons, oxidative stress and neuroinflammation. The classical therapeutic approach with L-DOPA is not able to control motor symptoms in the long term, thus new disease-modifying or neuroprotective treatments are urgently required in order to match such yet unmet clinical needs. Success in cell-based therapy has been accomplished at a clinical level with human fetal mesencephalic tissue, but ethical issues and a shortage of organs clearly underline the need for novel sources of dopaminergic neurons. Mesenchymal stem cells (MSCs) can be obtained from different adult and fetal tissues that are normally discarded as waste, including adipose tissue, placenta, umbilical cord, and dental tissues. Their neuroregenerative, anti-inflammatory and immunomodulatory properties are mainly mediated by the secretion of an array of bioactive molecules and are heightened when MSCs form tri-dimensional structures called spheroids. Not only can MSCs spontaneously produce neurotrophic factors (NFs) but they can be engineered to synthetize and secrete them in vivo. The aim of this review is to provide a picture of results gained with MSC secretome and spheroids in PD, as well as the possibility of harnessing MSC-based therapy with the use of nano- and micro-structured materials for NF delivery.

Keywords: Mesenchymal stem cells, secretome, spheroids, neurotrophic factors, hydrogels, microparticles, polymeric nanoparticles, lipid-based nanoparticles.

Tansey MG, Goldberg MS. Neuroinflammation in Parkinson’s disease: Its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 2010; 37(3): 510-8.
Kraft AD, Harry GJ. Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity. Int J Environ Res Public Health 2011; 8(7): 2980-3018.
Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol 2010; 6(4): 193-201.
Magrinelli F, Picelli A, Tocco P, et al. Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation. Parkinsons Dis 2016; 20169832839
Lindvall O, Bjorklund A. Cell therapy in Parkinson’s disease. NeuroRx 2004; 1(4): 382-93.
Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders--time for clinical translation? J Clin Invest 2010; 120(1): 29-40.
Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 2008; 14(5): 504-6.
Li JY, Englund E, Holton JL, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 2008; 14(5): 501-3.
Piccini P, Brooks DJ, Bjorklund A, et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient. Nat Neurosci 1999; 2(12): 1137-40.
Barker RA, Drouin-Ouellet J, Parmar M. Cell-based therapies for Parkinson disease-past insights and future potential. Nat Rev Neurol 2015; 11(9): 492-503.
Kefalopoulou Z, Politis M, Piccini P, et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: Two case reports. JAMA Neurol 2014; 71(1): 83-7.
Moore SF, Guzman NV, Mason SL, Williams-Gray CH, Barker RA. Which patients with Parkinson’s disease participate in clinical trials? One centre’s experiences with a new cell based therapy trial (TRANSEURO). J Parkinsons Dis 2014; 4(4): 671-6.
Barker RA, Studer L, Cattaneo E, Takahashi J. G-Force PD: A global initiative in coordinating stem cell-based dopamine treatments for Parkinson’s disease. NPJ Parkinsons Dis 2015; 1: 15017.
Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001; 344(10): 710-9.
Olanow CW, Goetz CG, Kordower JH, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 2003; 54(3): 403-14.
Brundin P, Barker RA, Parmar M. Neural grafting in Parkinson’s disease Problems and possibilities. Prog Brain Res 2010; 184: 265-94.
Lunn JS, Sakowski SA, Hur J, Feldman EL. Stem cell technology for neurodegenerative diseases. Ann Neurol 2011; 70(3): 353-61.
Suzuki M, Svendsen CN. Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis. Trends Neurosci 2008; 31(4): 192-8.
Lunn JS, Hefferan MP, Marsala M, Feldman EL. Stem cells: Comprehensive treatments for amyotrophic lateral sclerosis in conjunction with growth factor delivery. Growth Factors 2009; 27(3): 133-40.
Behrstock S, Ebert AD, Klein S, Schmitt M, Moore JM, Svendsen CN. Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF. Cell Transplant 2008; 17(7): 753-62.
Blurton-Jones M, Kitazawa M, Martinez-Coria H, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA 2009; 106(32): 13594-9.
Ebert AD, Barber AE, Heins BM, Svendsen CN. Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington’s disease. Exp Neurol 2010; 224(1): 155-62.
Xuan AG, Long DH, Gu HG, Yang DD, Hong LP, Leng SL. BDNF improves the effects of neural stem cells on the rat model of Alzheimer’s disease with unilateral lesion of fimbria-fornix. Neurosci Lett 2008; 440(3): 331-5.
Alvarez CV, Garcia-Lavandeira M, Garcia-Rendueles ME, et al. Defining stem cell types: Understanding the therapeutic potential of ESCs, ASCs, and iPS cells. J Mol Endocrinol 2012; 49(2): R89-R111.
Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282(5391): 1145-7.
English K, Wood KJ. Immunogenicity of embryonic stem cell-derived progenitors after transplantation. Curr Opin Organ Transplant 2011; 16(1): 90-5.
Blum B, Benvenisty N. The tumorigenicity of human embryonic stem cells. Adv Cancer Res 2008; 100: 133-58.
Xiao B, Ng HH, Takahashi R, Tan EK. Induced pluripotent stem cells in Parkinson’s disease: scientific and clinical challenges. J Neurol Neurosurg Psychiatry 2016; 87(7): 697-702.
Pires AO, Teixeira FG, Mendes-Pinheiro B, Serra SC, Sousa N, Salgado AJ. Old and new challenges in Parkinson’s disease therapeutics. Prog Neurobiol 2017; 156: 69-89.
Wernig M, Zhao JP, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 2008; 105(15): 5856-61.
lavaski-Joksimovic A, Bohn MC. Mesenchymal stem cells and neuroregeneration in Parkinson’s disease. Exp Neurol 2013; 247: 25-38.
Gugliandolo A, Bramanti P, Mazzon E. Mesenchymal stem cell therapy in Parkinson’s disease animal models. Curr Res Transl Med 2017; 65(2): 51-60.
Hermann A, Gastl R, Liebau S, et al. Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 2004; 117(Pt 19): 4411-22.
Mitchell KE, Weiss ML, Mitchell BM, et al. Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 2003; 21(1): 50-60.
Munoz-Elias G, Marcus AJ, Coyne TM, Woodbury D, Black IB. Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival. J Neurosci 2004; 24(19): 4585-95.
Phinney DG, Prockop DJ. Concise review: Mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells 2007; 25(11): 2896-902.
Dezawa M, Kanno H, Hoshino M, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 2004; 113(12): 1701-10.
Suon S, Yang M, Iacovitti L. Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson’s disease. Brain Res 2006; 1106(1): 46-51.
Fu YS, Cheng YC, Lin MY, et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: Potential therapeutic application for Parkinsonism. Stem Cells 2006; 24(1): 115-24.
Pacary E, Legros H, Valable S, et al. Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. J Cell Sci 2006; 119(Pt 13): 2667-78.
Kan I, Ben-Zur T, Barhum Y, et al. Dopaminergic differentiation of human mesenchymal stem cells-utilization of bioassay for tyrosine hydroxylase expression. Neurosci Lett 2007; 419(1): 28-33.
Trzaska KA, Kuzhikandathil EV, Rameshwar P. Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. Stem Cells 2007; 25(11): 2797-808.
Barzilay R, Kan I, Ben-Zur T, Bulvik S, Melamed E, Offen D. Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols. Stem Cells Dev 2008; 17(3): 547-54.
Li Y, Chen J, Wang L, Zhang L, Lu M, Chopp M. Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neurosci Lett 2001; 316(2): 67-70.
Sun Y, Selvaraj S, Pandey S, et al. MPP(+) decreases store-operated calcium entry and TRPC1 expression in Mesenchymal Stem Cell derived dopaminergic neurons. Sci Rep 2018; 8(1): 11715.
Singh M, Kakkar A, Sharma R, et al. Synergistic effect of BDNF and FGF2 in efficient generation of functional dopaminergic neurons from human mesenchymal stem cells. Sci Rep 2017; 7(1): 10378.
Venkatesh K, Sen D. Mesenchymal stem cells as a source of dopaminergic neurons: A potential cell based therapy for Parkinson’s disease. Curr Stem Cell Res Ther 2017; 12(4): 326-47.
Yang XY, Zhao EY, Zhuang WX, et al. LPA signaling is required for dopaminergic neuron development and is reduced through low expression of the LPA1 receptor in a 6-OHDA lesion model of Parkinson’s disease. Neurol Sci 2015; 36(11): 2027-33.
Nandy SB, Mohanty S, Singh M, Behari M, Airan B. Fibroblast Growth Factor-2 alone as an efficient inducer for differentiation of human bone marrow mesenchymal stem cells into dopaminergic neurons. J Biomed Sci 2014; 21: 83.
Datta I, Mishra S, Mohanty L, Pulikkot S, Joshi PG. Neuronal plasticity of human Wharton’s jelly mesenchymal stromal cells to the dopaminergic cell type compared with human bone marrow mesenchymal stromal cells. Cytotherapy 2011; 13(8): 918-32.
Wang Y, Yang J, Li H, Wang X, Zhu L, Fan M. Hypoxia promotes dopaminergic differentiation of mesenchymal stem cells and shows benefits for transplantation in a rat model of Parkinson’s disease. PLoS One 2013; 8(1)e54296
Bouchez G, Sensebe L, Vourc’h P, et al. Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson’s disease. Neurochem Int 2008; 52(7): 1332-42.
McCoy MK, Martinez TN, Ruhn KA, et al. Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson’s disease. Exp Neurol 2008; 210(1): 14-29.
Chao YX, He BP, Tay SS. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson’s disease. J Neuroimmunol 2009; 216(1-2): 39-50.
Khoo ML, Tao H, Meedeniya AC, Mackay-Sim A, Ma DD. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents. PLoS One 2011; 6(5)e19025
Neirinckx V, Marquet A, Coste C, Rogister B, Wislet-Gendebien S. Adult bone marrow neural crest stem cells and mesenchymal stem cells are not able to replace lost neurons in acute MPTP-lesioned mice. PLoS One 2013; 8(5)e64723
Blandini F, Cova L, Armentero MT, et al. Transplantation of undifferentiated human mesenchymal stem cells protects against 6-hydroxydopamine neurotoxicity in the rat. Cell Transplant 2010; 19(2): 203-17.
Sadan O, Bahat-Stromza M, Barhum Y, et al. Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of Parkinson disease. Stem Cells Dev 2009; 18(8): 1179-90.
Somoza R, Juri C, Baes M, Wyneken U, Rubio FJ. Intranigral transplantation of epigenetically induced BDNF-secreting human mesenchymal stem cells: Implications for cell-based therapies in Parkinson’s disease. Biol Blood Marrow Transplant 2010; 16(11): 1530-40.
Wang J, Wang X, Sun Z, Yang H, Shi S, Wang S. Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev 2010; 19(9): 1375-83.
Park HJ, Lee PH, Bang OY, Lee G, Ahn YH. Mesenchymal stem cells therapy exerts neuroprotection in a progressive animal model of Parkinson’s disease. J Neurochem 2008; 107(1): 141-51.
Coquery N, Blesch A, Stroh A, et al. Intrahippocampal transplantation of mesenchymal stromal cells promotes neuroplasticity. Cytotherapy 2012; 14(9): 1041-53.
Glavaski-Joksimovic A, Virag T, Chang QA, et al. Reversal of dopaminergic degeneration in a parkinsonian rat following micrografting of human bone marrow-derived neural progenitors. Cell Transplant 2009; 18(7): 801-14.
Weiss ML, Medicetty S, Bledsoe AR, et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 2006; 24(3): 781-92.
Kim YJ, Park HJ, Lee G, et al. Neuroprotective effects of human mesenchymal stem cells on dopaminergic neurons through anti-inflammatory action. Glia 2009; 57(1): 13-23.
Wang F, Yasuhara T, Shingo T, et al. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1alpha. BMC Neurosci 2010; 11: 52.
Kalra H, Drummen GP, Mathivanan S. Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int J Mol Sci 2016; 17(2): 170.
Yang Y, Hong Y, Cho E, Kim GB, Kim IS. Extracellular vesicles as a platform for membrane-associated therapeutic protein delivery. J Extracell Vesicles 2018; 7(1)1440131
Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci 2017; 18(9)E1852
Teixeira FG, Carvalho MM, Panchalingam KM, et al. Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson’s Disease. Stem Cells Transl Med 2017; 6(2): 634-46.
Cova L, Armentero MT, Zennaro E, et al. Multiple neurogenic and neurorescue effects of human mesenchymal stem cell after transplantation in an experimental model of Parkinson’s disease. Brain Res 2010; 1311: 12-27.
Sadan O, Melamed E, Offen D. Bone-marrow-derived mesenchymal stem cell therapy for neurodegenerative diseases. Expert Opin Biol Ther 2009; 9(12): 1487-97.
Sadan O, Shemesh N, Cohen Y, Melamed E, Offen D. Adult neurotrophic factor-secreting stem cells: a potential novel therapy for neurodegenerative diseases. Isr Med Assoc J 2009; 11(4): 201-4.
Cesarz Z, Tamama K. Spheroid Culture of Mesenchymal Stem Cells. Stem Cells Int 2016; 20169176357
Cui X, Hartanto Y, Zhang H. Advances in multicellular spheroids formation. J R Soc Interface 2017; 14(127)
Hsu SH, Huang GS, Feng F. Isolation of the multipotent MSC subpopulation from human gingival fibroblasts by culturing on chitosan membranes. Biomaterials 2012; 33(9): 2642-55.
Ribeiro JCV, Vieira RS, Melo IM, Araujo VMA, Lima V. Versatility of chitosan-based biomaterials and their use as scaffolds for tissue regeneration. ScientificWorldJournal 2017; 20178639898
Redondo-Castro E, Cunningham CJ, Miller J, Brown H, Allan SM, Pinteaux E. Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal stem cells in vitro by interleukin-1 priming. Stem Cell Res Ther 2018; 9(1): 11.
Schwerk A, Altschuler J, Roch M, et al. Human adipose-derived mesenchymal stromal cells increase endogenous neurogenesis in the rat subventricular zone acutely after 6-hydroxydopamine lesioning. Cytotherapy 2015; 17(2): 199-214.
Park S, Koh SE, Maeng S, Lee WD, Lim J, Lee YJ. Neural progenitors generated from the mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity. Placenta 2011; 32(3): 269-76.
Park S, Kim E, Koh SE, et al. Dopaminergic differentiation of neural progenitors derived from placental mesenchymal stem cells in the brains of Parkinson’s disease model rats and alleviation of asymmetric rotational behavior. Brain Res 2012; 1466: 158-66.
Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3(4): 393-403.
Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 2004; 103(5): 1669-75.
Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13(12): 4279-95.
Parolini O, Alviano F, Bagnara GP, et al. Concise review: Isolation and characterization of cells from human term placenta: Outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells 2008; 26(2): 300-11.
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 2000; 97(25): 13625-30.
Wagner W, Wein F, Seckinger A, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005; 33(11): 1402-16.
Noel D, Caton D, Roche S, et al. Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res 2008; 314(7): 1575-84.
Equbal Z, Mukhopadhyay A. Counting on mesenchymal stem cells: A hope for treating Parkinson’s disease. J Stem Cells Res. Rev Reprod 2016; 3(1): 1022.
Hayashi T, Wakao S, Kitada M, et al. Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques. J Clin Invest 2013; 123(1): 272-84.
Kumar A, Dudhal S, Sundari TA, et al. Dopaminergic-primed fetal liver mesenchymal stromal-like cells can reverse parkinsonian symptoms in 6-hydroxydopamine-lesioned mice. Cytotherapy 2016; 18(3): 307-19.
Rooney GE, Howard L, O’Brien T, Windebank AJ, Barry FP. Elevation of cAMP in mesenchymal stem cells transiently upregulates neural markers rather than inducing neural differentiation. Stem Cells Dev 2009; 18(3): 387-98.
Bertani N, Malatesta P, Volpi G, Sonego P, Perris R. Neurogenic potential of human mesenchymal stem cells revisited: Analysis by immunostaining, time-lapse video and microarray. J Cell Sci 2005; 118(Pt 17): 3925-36.
Lu P, Blesch A, Tuszynski MH. Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res 2004; 77(2): 174-91.
Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 2000; 61(4): 364-70.
Ma K, Fox L, Shi G, et al. Generation of neural stem cell-like cells from bone marrow-derived human mesenchymal stem cells. Neurol Res 2011; 33(10): 1083-93.
Ganat YM, Calder EL, Kriks S, et al. Identification of embryonic stem cell-derived midbrain dopaminergic neurons for engraftment. J Clin Invest 2012; 122(8): 2928-39.
Thompson LH, Bjorklund A. Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts. Prog Brain Res 2009; 175: 53-79.
Gu W, Zhang F, Xue Q, Ma Z, Lu P, Yu B. Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord. Neuropathology 2010; 30(3): 205-17.
Wilkins A, Kemp K, Ginty M, Hares K, Mallam E, Scolding N. Human bone marrow-derived mesenchymal stem cells secrete brain-derived neurotrophic factor which promotes neuronal survival in vitro. Stem Cell Res 2009; 3(1): 63-70.
Caplan AI, Correa D. The MSC: An injury drugstore. Cell Stem Cell 2011; 9(1): 11-5.
Chen J, Chopp M. Neurorestorative treatment of stroke: Cell and pharmacological approaches. NeuroRx 2006; 3(4): 466-73.
Lattanzi W, Geloso MC, Saulnier N, et al. Neurotrophic features of human adipose tissue-derived stromal cells: In vitro and in vivo studies. J Biomed Biotechnol 2011; 2011468705
Mezey E, Mayer B, Nemeth K. Unexpected roles for bone marrow stromal cells (or MSCs): A real promise for cellular, but not replacement, therapy. Oral Dis 2010; 16(2): 129-35.
Singer NG, Caplan AI. Mesenchymal stem cells: Mechanisms of inflammation. Annu Rev Pathol 2011; 6: 457-78.
Paul G, Anisimov SV. The secretome of mesenchymal stem cells: Potential implications for neuroregeneration. Biochimie 2013; 95(12): 2246-56.
Aizman I, Tate CC, McGrogan M, Case CC. Extracellular matrix produced by bone marrow stromal cells and by their derivative, SB623 cells, supports neural cell growth. J Neurosci Res 2009; 87(14): 3198-206.
Lu S, Lu C, Han Q, et al. Adipose-derived mesenchymal stem cells protect PC12 cells from glutamate excitotoxicity-induced apoptosis by upregulation of XIAP through PI3-K/Akt activation. Toxicology 2011; 279(1-3): 189-95.
Shintani A, Nakao N, Kakishita K, Itakura T. Protection of dopamine neurons by bone marrow stromal cells. Brain Res 2007; 1186: 48-55.
Park HJ, Shin JY, Lee BR, Kim HO, Lee PH. Mesenchymal stem cells augment neurogenesis in the subventricular zone and enhance differentiation of neural precursor cells into dopaminergic neurons in the substantia nigra of a parkinsonian model. Cell Transplant 2012; 21(8): 1629-40.
Cerri S, Greco R, Levandis G, et al. Intracarotid infusion of mesenchymal stem cells in an animal model of Parkinson’s disease, focusing on cell distribution and neuroprotective and behavioral effects. Stem Cells Transl Med 2015; 4(9): 1073-85.
Teixeira FG, Carvalho MM, Panchalingam KM, et al. Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson’s disease. Stem Cells Transl Med 2017; 6(2): 634-46.
Schwerk A, Altschuler J, Roch M, et al. Adipose-derived human mesenchymal stem cells induce long-term neurogenic and anti-inflammatory effects and improve cognitive but not motor performance in a rat model of Parkinson’s disease. Regen Med 2015; 10(4): 431-46.
Berg J, Roch M, Altschuler J, et al. Human adipose-derived mesenchymal stem cells improve motor functions and are neuroprotective in the 6-hydroxydopamine-rat model for Parkinson’s disease when cultured in monolayer cultures but suppress hippocampal neurogenesis and hippocampal memory function when cultured in spheroids. Stem Cell Rev Rep 2015; 11(1): 133-49.
Chierchia A, Chirico N, Boeri L, et al. Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson’s disease related toxin 6-hydroxydopamine. Eur J Pharm Biopharm 2017; 121: 113-20.
Calzarossa C, Bossolasco P, Besana A, et al. Neurorescue effects and stem properties of chorionic villi and amniotic progenitor cells. Neuroscience 2013; 234: 158-72.
Kim HW, Lee HS, Kang JM, et al. Dual Effects of Human Placenta-Derived Neural Cells on Neuroprotection and the Inhibition of Neuroinflammation in a Rodent Model of Parkinson’s Disease. Cell Transplant 2018; 27(5): 814-30.
Fujii H, Matsubara K, Sakai K, et al. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats. Brain Res 2015; 1613: 59-72.
Jarmalaviciute A, Tunaitis V, Pivoraite U, Venalis A, Pivoriunas A. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis. Cytotherapy 2015; 17(7): 932-9.
Mathieu P, Roca V, Gamba C, Del Pozo A, Pitossi F. Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an immunocompetent animal model of Parkinson’s disease. J Neuroimmunol 2012; 246(1-2): 43-50.
Yang S, Sun HM, Yan JH, et al. Conditioned medium from human amniotic epithelial cells may induce the differentiation of human umbilical cord blood mesenchymal stem cells into dopaminergic neuron-like cells. J Neurosci Res 2013; 91(7): 978-86.
Pires AO, Neves-Carvalho A, Sousa N, Salgado AJ. The secretome of bone marrow and wharton jelly derived mesenchymal stem cells induces differentiation and neurite outgrowth in SH-SY5Y cells. Stem Cells Int 2014; 2014438352
Mendes Filho D, Ribeiro PDC, Oliveira LF, et al. Therapy with mesenchymal stem cells in Parkinson Disease: History and perspectives. Neurologist 2018; 23(4): 141-7.
Venkataramana NK, Kumar SK, Balaraju S, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res 2010; 155(2): 62-70.
Yang W, Qiang D, Zhang M, et al. Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models. Int Immunopharmacol 2011; 11(6): 683-92.
Drago D, Cossetti C, Iraci N, et al. The stem cell secretome and its role in brain repair. Biochimie 2013; 95(12): 2271-85.
Teixeira FG, Carvalho MM, Sousa N, Salgado AJ. Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci 2013; 70(20): 3871-82.
Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 2013; 138(2): 155-75.
Hirano T, Ishihara K, Hibi M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 2000; 19(21): 2548-56.
Pucci S, Mazzarelli P, Missiroli F, Regine F, Ricci F. Neuroprotection: VEGF, IL-6, and clusterin: The dark side of the moon. Prog Brain Res 2008; 173: 555-73.
Xiong N, Zhang Z, Huang J, et al. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson’s disease. Gene Ther 2011; 18(4): 394-402.
D’Adamio L. Role of Cystatin C in Neuroprotection and Its Therapeutic Implications. Am J Pathol 2010; 177(5): 2163-5.
Hoffmann MC, Nitsch C, Scotti AL, Reinhard E, Monard D. The Prolonged Presence of Glia-Derived Nexin, an Endogenous Protease Inhibitor, in the Hippocampus after Ischemia-Induced Delayed Neuronal Death. Neuroscience 1992; 49(2): 397-408.
Nonaka M, Fukuda M. Galectin-1 for neuroprotection? Immunity 2012; 37(2): 187-9.
Yabe T, Sanagi T, Yamada H. The Neuroprotective Role of PEDF: Implication for the Therapy of Neurological Disorders. Curr Mol Med 2010; 10(3): 259-66.
Falk T, Gonzalez RT, Sherman SJ. The Yin and Yang of VEGF and PEDF: Multifaceted Neurotrophic Factors and Their Potential in the Treatment of Parkinson’s Disease. Int J Mol Sci 2010; 11(8): 2875-900.
Strem BM, Hicok KC, Zhu M, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 2005; 54(3): 132-41.
Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24(5): 1294-301.
Zhang HT, Liu ZL, Yao XQ, Yang ZJ, Xu RX. Neural differentiation ability of mesenchymal stromal cells from bone marrow and adipose tissue: a comparative study. Cytotherapy 2012; 14(10): 1203-14.
Izadpanah R, Trygg C, Patel B, et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006; 99(5): 1285-97.
Heo JS, Choi Y, Kim HS, Kim HO. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue. Int J Mol Med 2016; 37(1): 115-25.
Safford KM, Hicok KC, Safford SD, et al. Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun 2002; 294(2): 371-9.
Ashjian PH, Elbarbary AS, Edmonds B, et al. In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg 2003; 111(6): 1922-31.
Ikegame Y, Yamashita K, Hayashi S, et al. Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy 2011; 13(6): 675-85.
Boulland JL, Mastrangelopoulou M, Boquest AC, et al. Epigenetic regulation of nestin expression during neurogenic differentiation of adipose tissue stem cells. Stem Cells Dev 2013; 22(7): 1042-52.
Kingham PJ, Kolar MK, Novikova LN, Novikov LN, Wiberg M. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair. Stem Cells Dev 20141; 23(7): 741-54.
Kapur SK, Katz AJ. Review of the adipose derived stem cell secretome. Biochimie 2013; 95(12): 2222-8.
Brohlin M, Kingham PJ, Novikova LN, Novikov LN, Wiberg M. Aging effect on neurotrophic activity of human mesenchymal stem cells. PLoS One 2012; 7(9)e45052
Moriyama M, Moriyama H, Ueda A, et al. Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling. BMC Cell Biol 2012; 13: 21.
Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K. Glial differentiation of human adipose-derived stem cells: Implications for cell-based transplantation therapy. Neuroscience 2013; 236: 55-65.
Alviano F, Fossati V, Marchionni C, et al. Term Amniotic membrane is a high throughput source for multipotent Mesenchymal Stem Cells with the ability to differentiate into endothelial cells in vitro. BMC Dev Biol 2007; 7: 11.
Ledesma-Martinez E, Mendoza-Nunez VM, Santiago-Osorio E. Mesenchymal stem cells derived from dental pulp: A review. Stem Cells Int 2016; 20164709572
Kaukua N, Shahidi MK, Konstantinidou C, et al. Glial origin of mesenchymal stem cells in a tooth model system. Nature 2014; 513(7519): 551-4.
Pierdomenico L, Bonsi L, Calvitti M, et al. Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation 2005; 80(6): 836-42.
Isobe Y, Koyama N, Nakao K, et al. Comparison of human mesenchymal stem cells derived from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous tooth pulp. Int J Oral Maxillofac Surg 2016; 45(1): 124-31.
Stanko P, Altanerova U, Jakubechova J, Repiska V, Altaner C. Dental mesenchymal stem/stromal cells and their exosomes. Stem Cells Int 2018; 20188973613
Troyer DL, Weiss ML. Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 2008; 26(3): 591-9.
Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 2007; 25(6): 1384-92.
Jin HJ, Bae YK, Kim M, et al. Comparative analysis of human mesenchymal stem cells from bone marrow, adipose tissue, and umbilical cord blood as sources of cell therapy. Int J Mol Sci 2013; 14(9): 17986-8001.
Aliaghaei A, Gardaneh M, Maghsoudi N, Salehinejad P, Gharib E. Dopaminergic induction of umbilical cord mesenchymal stem cells by conditioned medium of choroid plexus epithelial cells reduces apomorphine-induced rotation in Parkinsonian rats. Arch Iran Med 2016; 19(8): 561-70.
Ribeiro CA, Fraga JS, Graos M, et al. The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations. Stem Cell Res Ther 2012; 3(3): 18.
Fraga JS, Silva NA, Lourenco AS, et al. Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations. Biochimie 2013; 95(12): 2297-303.
Inden M, Yanagisawa D, Hijioka M, Kitamura Y. Therapeutic effects of mesenchymal stem cells for Parkinson’s disease. Ann Neurodegener Dis 2016; 1(1): 1002.
Kurtz A. Mesenchymal stem cell delivery routes and fate. Int J Stem Cells 2008; 1(1): 1-7.
Pantcheva P, Reyes S, Hoover J, Kaelber S, Borlongan CV. Treating non-motor symptoms of Parkinson’s disease with transplantation of stem cells. Expert Rev Neurother 2015; 15(10): 1231-40.
Kassis I, Petrou P, Vaknin-Dembinsky A, Karussis D. Mesenchymal stem cells in neurological diseases. Clin Invest 2013; 3(2): 173-89.
Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): A systematic review and meta-analysis of clinical trials. PLoS One 2012; 7(10)e47559
Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med 2011; 9: 29.
Ramot Y, Steiner M, Morad V, et al. Pulmonary thrombosis in the mouse following intravenous administration of quantum dot-labeled mesenchymal cells. Nanotoxicology 2010; 4(1): 98-105.
Danielyan L, Schafer R, von Ameln-Mayerhofer A, et al. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Res 2011; 14(1): 3-16.
Danielyan L, Beer-Hammer S, Stolzing A, et al. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease. Cell Transplant 2014; 23(Suppl. 1): S123-39.
Kitada M, Dezawa M. Parkinson’s disease and mesenchymal stem cells: Potential for cell-based therapy. Parkinsons Dis 2012; 2012873706
Ren G, Chen X, Dong F, et al. Concise review: Mesenchymal stem cells and translational medicine: Emerging issues. Stem Cells Transl Med 2012; 1(1): 51-8.
Kunter U, Rong S, Boor P, et al. Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J Am Soc Nephrol 2007; 18(6): 1754-64.
Ren G, Zhao X, Wang Y, et al. CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFalpha. Cell Stem Cell 2012; 11(6): 812-24.
Senst C, Nazari-Shafti T, Kruger S, et al. Prospective dual role of mesenchymal stem cells in breast tumor microenvironment. Breast Cancer Res Treat 2013; 137(1): 69-79.
Huang WH, Chang MC, Tsai KS, Hung MC, Chen HL, Hung SC. Mesenchymal stem cells promote growth and angiogenesis of tumors in mice. Oncogene 2013; 32(37): 4343-54.
Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449(7162): 557-63.
Liu S, Ginestier C, Ou SJ, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011; 71(2): 614-24.
Spaeth EL, Dembinski JL, Sasser AK, et al. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS One 2009; 4(4)e4992
Zhu Y, Sun Z, Han Q, et al. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia 2009; 23(5): 925-33.
Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D, Dazzi F. Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: Impact on in vivo tumor growth. Leukemia 2007; 21(2): 304-10.
Jimenez G, Hackenberg M, Catalina P, et al. Mesenchymal stem cell’s secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile. Cancer Lett 2018; 429: 78-88.
Paul G, Sullivan AM. Trophic factors for Parkinson’s disease: Where are we and where do we go from here? Eur J Neurosci 2018. [Epub ahead of print].
Geral C, Angelova A, Lesieur S. From molecular to nanotechnology strategies for delivery of neurotrophins: Emphasis on Brain-Derived Neurotrophic Factor (BDNF). Pharmaceutics 2013; 5(1): 127-67.
Balaratnasingam S, Janca A. Brain derived neurotrophic factor: A novel neurotrophin involved in psychiatric and neurological disorders. Pharmacol Ther 2012; 134(1): 116-24.
Aron L, Klein R. Repairing the parkinsonian brain with neurotrophic factors. Trends Neurosci 2011; 34(2): 88-100.
Oertel W, Schulz JB. Current and experimental treatments of Parkinson disease: A guide for neuroscientists. J Neurochem 2016; 139(Suppl. 1): 325-37.
Meissner WG, Frasier M, Gasser T, et al. Priorities in Parkinson’s disease research. Nat Rev Drug Discov 2011; 10(5): 377-93.
Di Gioia S, Trapani A, Mandracchia D, et al. Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-beta-cyclodextrin based nanoparticles. Eur J Pharm Biopharm 2015; 94: 180-93.
Lindvall O, Wahlberg LU. Encapsulated cell biodelivery of GDNF: A novel clinical strategy for neuroprotection and neuroregeneration in Parkinson’s disease? Exp Neurol 2008; 209(1): 82-8.
Akerud P, Canals JM, Snyder EY, Arenas E. Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson’s disease. J Neurosci 2001; 21(20): 8108-18.
Glavaski-Joksimovic A, Virag T, Mangatu TA, McGrogan M, Wang XS, Bohn MC. Glial cell line-derived neurotrophic factor-secreting genetically modified human bone marrow-derived mesenchymal stem cells promote recovery in a rat model of Parkinson’s disease. J Neurosci Res 2010; 88(12): 2669-81.
Jinfeng L, Yunliang W, Xinshan L, et al. The Effect of MSCs derived from the human umbilical cord transduced by fibroblast growth factor-20 on Parkinson’s disease. Stem Cells Int 2016; 20165016768
Hoban DB, Howard L, Dowd E. GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease. Neuroscience 2015; 303: 402-11.
Bjorklund A, Kirik D, Rosenblad C, Georgievska B, Lundberg C, Mandel RJ. Towards a neuroprotective gene therapy for Parkinson’s disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res 2000; 886(1-2): 82-98.
Kirik D, Rosenblad C, Bjorklund A, Mandel RJ. Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson’s model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. J Neurosci 2000; 20(12): 4686-700.
Eslamboli A, Cummings RM, Ridley RM, et al. Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus). Exp Neurol 2003; 184(1): 536-48.
Decressac M, Ulusoy A, Mattsson B, et al. GDNF fails to exert neuroprotection in a rat alpha-synuclein model of Parkinson’s disease. Brain 2011; 134(Pt 8): 2302-11.
Decressac M, Kadkhodaei B, Mattsson B, Laguna A, Perlmann T, Bjorklund A. alpha-Synuclein-induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Sci Transl Med 2012; 4(163)163ra56
Horger BA, Nishimura MC, Armanini MP, et al. Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 1998; 18(13): 4929-37.
Grondin R, Zhang Z, Ai Y, et al. Intraputamenal infusion of exogenous neurturin protein restores motor and dopaminergic function in the globus pallidus of MPTP-lesioned rhesus monkeys. Cell Transplant 2008; 17(4): 373-81.
Gasmi M, Brandon EP, Herzog CD, et al. AAV2-mediated delivery of human neurturin to the rat nigrostriatal system: Long-term efficacy and tolerability of CERE-120 for Parkinson’s disease. Neurobiol Dis 2007; 27(1): 67-76.
Kordower JH, Herzog CD, Dass B, et al. Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Ann Neurol 2006; 60(6): 706-15.
Kordower JH, Bjorklund A. Trophic factor gene therapy for Parkinson’s disease. Mov Disord 2013; 28(1): 96-109.
Marks WJ Jr, Bartus RT, Siffert J, et al. Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol 2010; 9(12): 1164-72.
Olanow CW, Bartus RT, Volpicelli-Daley LA, Kordower JH. Trophic factors for Parkinson’s disease: To live or let die. Mov Disord 2015; 30(13): 1715-24.
Thorne RG, Frey WH 2nd. Delivery of neurotrophic factors to the central nervous system: Pharmacokinetic considerations. Clin Pharmacokinet 2001; 40(12): 907-46.
Zuccato C, Cattaneo E. Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 2009; 5(6): 311-22.
Fan CH, Ting CY, Lin CY, et al. Noninvasive, targeted, and Non-viral ultrasound-mediated GDNF-plasmid delivery for treatment of Parkinson’s disease. Sci Rep 2016; 6: 19579.
Bleier BS, Kohman RE, Guerra K, et al. Heterotopic mucosal grafting enables the delivery of therapeutic neuropeptides across the blood brain barrier. Neurosurgery 2016; 78(3): 448-57. discussion 57.
Peterson AL, Nutt JG. Treatment of Parkinson’s disease with trophic factors. Neurotherapeutics 2008; 5(2): 270-80.
Dhuria SV, Hanson LR, Frey WH 2nd. Intranasal delivery to the central nervous system: Mechanisms and experimental considerations. J Pharm Sci 2010; 99(4): 1654-73.
Mistry A, Stolnik S, Illum L. Nose-to-brain delivery: Investigation of the transport of nanoparticles with different surface characteristics and sizes in excised porcine olfactory epithelium. Mol Pharm 2015; 12(8): 2755-66.
Pathak K, Akhtar N. Nose to brain delivery of nanoformulations for neurotherapeutics in Parkinson’s disease: Defining the preclinical, clinical and toxicity issues. Curr Drug Deliv 2016. [Epub ahead of print].
Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev 2012; 64(7): 614-28.
Migliore MM, Ortiz R, Dye S, Campbell RB, Amiji MM, Waszczak BL. Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson’s disease. Neuroscience 2014; 274: 11-23.
Aly AE, Waszczak BL. Intranasal gene delivery for treating Parkinson’s disease: Overcoming the blood-brain barrier. Expert Opin Drug Deliv 2015; 12(12): 1923-41.
Danielyan L, Schafer R, von Ameln-Mayerhofer A, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol 2009; 88(6): 315-24.
Di Gioia S, Trapani A, Castellani S, et al. Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier. Pulm Pharmacol Ther 2015; 34: 8-24.
Frim DM, Uhler TA, Galpern WR, Beal MF, Breakefield XO, Isacson O. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci USA 1994; 91(11): 5104-8.
Levivier M, Przedborski S, Bencsics C, Kang UJ. Intrastriatal implantation of fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease. J Neurosci 1995; 15(12): 7810-20.
Nakahara Y, Gage FH, Tuszynski MH. Grafts of fibroblasts genetically modified to secrete NGF, BDNF, NT-3, or basic FGF elicit differential responses in the adult spinal cord. Cell Transplant 1996; 5(2): 191-204.
Man JHK, Groenink L, Caiazzo M. Cell reprogramming approaches in gene- and cell-based therapies for Parkinson’s disease. J Control Release 2018; 286: 114-24.
Staudt MD, Di Sebastiano AR, Xu H, et al. Advances in neurotrophic factor and cell-based therapies for Parkinson’s disease: A mini-review. Gerontology 2016; 62(3): 371-80.
Bale S, Khurana A, Reddy AS, Singh M, Godugu C. Overview on therapeutic applications of microparticulate drug delivery systems. Crit Rev Ther Drug Carrier Syst 2016; 33(4): 309-61.
Angelova A, Angelov B, Drechsler M, Lesieur S. Neurotrophin delivery using nanotechnology. Drug Discov Today 2013; 18(23-24): 1263-71.
Yi X, Manickam DS, Brynskikh A, Kabanov AV. Agile delivery of protein therapeutics to CNS. J Control Release 2014; 190: 637-63.
Beija M, Salvayre R, Lauth-de Viguerie N, Marty JD. Colloidal systems for drug delivery: From design to therapy. Trends Biotechnol 2012; 30(9): 485-96.
Polak P, Shefi O. Nanometric agents in the service of neuroscience: Manipulation of neuronal growth and activity using nanoparticles. Nanomedicine 2015; 11(6): 1467-79.
Kreuter J, Shamenkov D, Petrov V, et al. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J Drug Target 2002; 10(4): 317-25.
Denora N, Trapani A, Laquintana V, Lopedota A, Trapani G. Recent advances in medicinal chemistry and pharmaceutical technology-strategies for drug delivery to the brain. Curr Top Med Chem 2009; 9(2): 182-96.
Kiparissides C, Kammona O. Nanoscale carriers for targeted delivery of drugs and therapeutic biomolecules. Can J Chem Eng 2013; 91: 638-51.
Hoban DB, Newland B, Moloney TC, Howard L, Pandit A, Dowd E. The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel. Biomaterials 2013; 34(37): 9420-9.
Kandalam S, Sindji L, Delcroix GJ, et al. Pharmacologically active microcarriers delivering BDNF within a hydrogel: Novel strategy for human bone marrow-derived stem cells neural/neuronal differentiation guidance and therapeutic secretome enhancement. Acta Biomater 2017; 49: 167-80.
Garbayo E, Ansorena E, Lanciego JL, Aymerich MS, Blanco-Prieto MJ. Sustained release of bioactive glycosylated glial cell-line derived neurotrophic factor from biodegradable polymeric microspheres. Eur J Pharm Biopharm 2008; 69(3): 844-51.
Santos D, Gonzalez-Perez F, Giudetti G, et al. Preferential enhancement of sensory and motor axon regeneration by combining extracellular matrix components with neurotrophic factors. Int J Mol Sci 2016; 18(1)E65
Santos D, Gonzalez-Perez F, Navarro X, Del Valle J. Dose-dependent differential effect of neurotrophic factors on in vitro and in vivo regeneration of motor and sensory neurons. Neural Plast 2016; 20164969523
Santos D, Giudetti G, Micera S, Navarro X, Del Valle J. Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo. Brain Res 2016; 1636: 93-106.
Garbayo E, Montero-Menei CN, Ansorena E, Lanciego JL, Aymerich MS, Blanco-Prieto MJ. Effective GDNF brain delivery using microspheres-a promising strategy for Parkinson’s disease. J Control Release 2009; 135(2): 119-26.
Jollivet C, Aubert-Pouessel A, Clavreul A, et al. Striatal implantation of GDNF releasing biodegradable microspheres promotes recovery of motor function in a partial model of Parkinson’s disease. Biomaterials 2004; 25(5): 933-42.
Jollivet C, Aubert-Pouessel A, Clavreul A, et al. Long-term effect of intra-striatal glial cell line-derived neurotrophic factor-releasing microspheres in a partial rat model of Parkinson’s disease. Neurosci Lett 2004; 356(3): 207-10.
Garbayo E, Ansorena E, Lana H, et al. Brain delivery of microencapsulated GDNF induces functional and structural recovery in parkinsonian monkeys. Biomaterials 2016; 110: 11-23.
Zeng W, Liu Z, Li Y, et al. Development and characterization of cores-shell poly(lactide-co-glycolide)-chitosan microparticles for sustained release of GDNF. Colloids Surf B Biointerfaces 2017; 159: 791-9.
Georgievska B, Kirik D, Bjorklund A. Aberrant sprouting and downregulation of tyrosine hydroxylase in lesioned nigrostriatal dopamine neurons induced by long-lasting overexpression of glial cell line derived neurotrophic factor in the striatum by lentiviral gene transfer. Exp Neurol 2002; 177(2): 461-74.
Blits B, Carlstedt TP, Ruitenberg MJ, et al. Rescue and sprouting of motoneurons following ventral root avulsion and reimplantation combined with intraspinal adeno-associated viral vector-mediated expression of glial cell line-derived neurotrophic factor or brain-derived neurotrophic factor. Exp Neurol 2004; 189(2): 303-16.
Gujral C, Minagawa Y, Fujimoto K, Kitano H, Nakaji-Hirabayashi T. Biodegradable microparticles for strictly regulating the release of neurotrophic factors. J Control Release 2013; 168(3): 307-16.
Herran E, Ruiz-Ortega JA, Aristieta A, et al. In vivo administration of VEGF- and GDNF-releasing biodegradable polymeric microspheres in a severe lesion model of Parkinson’s disease. Eur J Pharm Biopharm 2013; 85(3 Pt B): 1183-90.
Tatard VM, Sindji L, Branton JG, et al. Pharmacologically active microcarriers releasing glial cell line - derived neurotrophic factor: Survival and differentiation of embryonic dopaminergic neurons after grafting in hemiparkinsonian rats. Biomaterials 2007; 28(11): 1978-88.
Moradian H, Keshvari H, Fasehee H, Dinarvand R, Faghihi S. Combining NT3-overexpressing MSCs and PLGA microcarriers for brain tissue engineering: A potential tool for treatment of Parkinson’s disease. Mater Sci Eng C Mater Biol Appl 2017; 76: 934-43.
Kurakhmaeva KB, Djindjikhashvili IA, Petrov VE, et al. Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles. J Drug Target 2009; 17(8): 564-74.
Peng YS, Lai PL, Peng S, et al. Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier. Int J Nanomedicine 2014; 9: 3163-74.
Aragon J, Salerno S, De Bartolo L, Irusta S, Mendoza G. Polymeric electrospun scaffolds for bone morphogenetic protein 2 delivery in bone tissue engineering. J Colloid Interface Sci 2018; 531: 126-37.
Jiang Y, Fay JM, Poon CD, et al. Nanoformulation of brain-derived neurotrophic factor with target receptor-triggered-release in the central nervous system. Adv Funct Mater 2018; 28(6)1703982
Liang Y, Liu Z, Shuai X, et al. Delivery of cationic polymer-siRNA nanoparticles for gene therapies in neural regeneration. Biochem Biophys Res Commun 2012; 421(4): 690-5.
Yurek D, Hasselrot U, Sesenoglu-Laird O, Padegimas L, Cooper M. Intracerebral injections of DNA nanoparticles encoding for a therapeutic gene provide partial neuroprotection in an animal model of neurodegeneration. Nanomedicine 2017; 13(7): 2209-17.
Huang X, Li M, Bruni R, Messa P, Cellesi F. The effect of thermosensitive liposomal formulations on loading and release of high molecular weight biomolecules. Int J Pharm 2017; 524(1-2): 279-89.
Xing Y, Wen CY, Li ST, Xia ZX. Non-viral liposome-mediated transfer of brain-derived neurotrophic factor across the blood-brain barrier. Neural Regen Res 2016; 11(4): 617-22.
Wu S, Li G, Li X, et al. Transport of glial cell line-derived neurotrophic factor into liposomes across the blood-brain barrier: in vitro and in vivo studies. Int J Mol Sci 2014; 15(3): 3612-23.
Trapani A, Tripodo G, Mandracchia D, et al. Glutathione-loaded solid lipid nanoparticles based on Gelucire® 50/13: Spectroscopic characterization and interactions with fish cells. J Drug Deliv Sci Technol 2018; 47: 359-66.
Matougui N, Boge L, Groo AC, et al. Lipid-based nanoformulations for peptide delivery. Int J Pharm 2016; 502(1-2): 80-97.
Becker Peres L, de Araujo PHH, Sayer C. Solid lipid nanoparticles for encapsulation of hydrophilic drugs by an organic solvent free double emulsion technique. Colloids Surf B Biointerfaces 2016; 140: 317-23.
Ali J, Ali M, Baboota S, et al. Potential of nanoparticulate drug delivery systems by intranasal administration. Curr Pharm Des 2010; 16(14): 1644-53.
Angelova A, Angelov B, Drechsler M, Garamus VM, Lesieur S. Protein entrapment in PEGylated lipid nanoparticles. Int J Pharm 2013; 454(2): 625-32.
Gartziandia O, Herran E, Pedraz JL, Carro E, Igartua M, Hernandez RM. Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration. Colloids Surf B Biointerfaces 2015; 134: 304-13.
Gartziandia O, Egusquiaguirre SP, Bianco J, et al. Nanoparticle transport across in vitro olfactory cell monolayers. Int J Pharm 2016; 499(1-2): 81-9.
Hernando S, Herran E, Figueiro-Silva J, et al. Intranasal Administration of TAT-Conjugated Lipid Nanocarriers Loading GDNF for Parkinson’s Disease. Mol Neurobiol 2018; 55(1): 145-55.
Zhao YZ, Li X, Lu CT, et al. Gelatin nanostructured lipid carriers-mediated intranasal delivery of basic fibroblast growth factor enhances functional recovery in hemiparkinsonian rats. Nanomedicine 2014; 10(4): 755-64.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [549 - 569]
Pages: 21
DOI: 10.2174/1574888X14666190301150210
Price: $58

Article Metrics

PDF: 27