Journal Home > Volume 9 , Issue 2
Journal of Neurorestoratology 2021, 9(2): 117-136 https://doi.org/10.26599/JNR.2021.9040010
Research Article | Open Access | Issue | Published: 05 June 2021

Improved survival in amyotrophic lateral sclerosis patients following autologous bone marrow mononuclear cell therapy: a long term 10-year retrospective study

Show Author's Information Alok Sharma1,  Hemangi Sane2,  Amruta Paranjape2,3( ),  Ritu Varghese2,  Vivek Nair3,  Hema Biju3,  Dhanashree Sawant2,  Nandini Gokulchandran1,  Prerna Badhe4
Department of Medical Services and Clinical Research, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Department of Research and Development, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Department of Neurorehabilitation, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Department of Regenerative Laboratory Services, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Keywords:
cell therapy, autologous bone marrow mononuclear cells, cellular therapy, amyotrophic lateral sclerosis, motor neuron disease, pre-menopausal women, pre-andropausal men
Cite this article:
Sharma A, Sane H, Paranjape A, et al. Improved survival in amyotrophic lateral sclerosis patients following autologous bone marrow mononuclear cell therapy: a long term 10-year retrospective study. Journal of Neurorestoratology, 2021, 9(2): 117-136. https://doi.org/10.26599/JNR.2021.9040010
Download citation
EndNote(RIS)
BibTeX

938

Views

64

Downloads

Citations

5

Crossref

5

WoS

0

Scopus

N/A

CSCD

Abstract Full text About this article
Background:

Promising results from previous studies using cell therapy have paved the way for an innovative treatment option for amyotrophic lateral sclerosis (ALS). There is considerable evidence of immune and inflammatory abnormalities in ALS. Bone marrow mononuclear cells (BMMNCs) possess immunomodulatory properties and could contribute to slowing of disease progression.

Objective:

Aim of our study was to evaluate the long-term effect of autologous BMMNCs combined with standard treatment on survival duration in a large population and to evaluate effect of type of onset and hormonal status on survival duration in the intervention group.

Methods:

This controlled, retrospective study spanned over 10 years, 5 months; included 216 patients with probable or definite ALS, 150 in intervention group receiving autologous BMMNCs and standard treatment, and 66 in control group receiving only standard treatment. The estimated survival duration of control group and intervention group was computed and compared using Kaplan Meier analysis. Survival duration of patients with different types of onset and hormonal status was compared within the intervention group.

Results:

None of the patients reported any major adverse events related to cell administration or the procedure. Kaplan Meier analysis estimated survival duration in the intervention group to be 91.7 months while 49.7 months in the control group (p = 0.008). Within the intervention group, estimated survival was significantly higher (p = 0.013) in patients with limb onset (102.3 months) vs. bulbar onset (49.9 months); premenopausal women (93.1 months) vs. postmenopausal women (57.6 months) (p = 0.002); and preandropausal men (153.7 months) vs. postandropausal males (56.5 months) (p = 0.006).

Conclusion:

Cell therapy using autologous BMMNCs along with standard treatment offers a promising and safe option for ALS with the potential of long term beneficial effect and increased survival. Limb onset patients, premenopausal women and men ≤ 40 years of age demonstrated better treatment efficacy.


menu
Abstract
Full text
Outline
About this article

Improved survival in amyotrophic lateral sclerosis patients following autologous bone marrow mononuclear cell therapy: a long term 10-year retrospective study

Show Author's information Alok Sharma1, Hemangi Sane2, Amruta Paranjape2,3( ), Ritu Varghese2, Vivek Nair3, Hema Biju3, Dhanashree Sawant2, Nandini Gokulchandran1, Prerna Badhe4
Department of Medical Services and Clinical Research, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Department of Research and Development, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Department of Neurorehabilitation, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
Department of Regenerative Laboratory Services, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India

Abstract

Background:

Promising results from previous studies using cell therapy have paved the way for an innovative treatment option for amyotrophic lateral sclerosis (ALS). There is considerable evidence of immune and inflammatory abnormalities in ALS. Bone marrow mononuclear cells (BMMNCs) possess immunomodulatory properties and could contribute to slowing of disease progression.

Objective:

Aim of our study was to evaluate the long-term effect of autologous BMMNCs combined with standard treatment on survival duration in a large population and to evaluate effect of type of onset and hormonal status on survival duration in the intervention group.

Methods:

This controlled, retrospective study spanned over 10 years, 5 months; included 216 patients with probable or definite ALS, 150 in intervention group receiving autologous BMMNCs and standard treatment, and 66 in control group receiving only standard treatment. The estimated survival duration of control group and intervention group was computed and compared using Kaplan Meier analysis. Survival duration of patients with different types of onset and hormonal status was compared within the intervention group.

Results:

None of the patients reported any major adverse events related to cell administration or the procedure. Kaplan Meier analysis estimated survival duration in the intervention group to be 91.7 months while 49.7 months in the control group (p = 0.008). Within the intervention group, estimated survival was significantly higher (p = 0.013) in patients with limb onset (102.3 months) vs. bulbar onset (49.9 months); premenopausal women (93.1 months) vs. postmenopausal women (57.6 months) (p = 0.002); and preandropausal men (153.7 months) vs. postandropausal males (56.5 months) (p = 0.006).

Conclusion:

Cell therapy using autologous BMMNCs along with standard treatment offers a promising and safe option for ALS with the potential of long term beneficial effect and increased survival. Limb onset patients, premenopausal women and men ≤ 40 years of age demonstrated better treatment efficacy.

Keywords: cell therapy, autologous bone marrow mononuclear cells, cellular therapy, amyotrophic lateral sclerosis, motor neuron disease, pre-menopausal women, pre-andropausal men

References(107)

[1]
Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2001, 2(11): 806-819.
DOI Google Scholar
[2]
Wijesekera LC, Nigel Leigh P. Amyotrophic lateral sclerosis. Orphanet J Rare Dis 2009, 4(1): 1-22.
DOI Google Scholar
[3]
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012(3): CD001447.
DOI Google Scholar
[4]
Tanaka M, Sakata T, Palumbo J, et al. A 24-week, phase III, double-blind, parallel-group study of edaravone (MCI-186) for treatment of amyotrophic lateral sclerosis (ALS). Neurology 2016, 86(16 Supl): P3. 189.
Google Scholar
[5]
Oskarsson B, Gendron TF, Staff NP. Amyotrophic lateral sclerosis: an update for 2018. Mayo Clin Proc 2018, 93(11): 1617-1628.
DOI Google Scholar
[6]
Tanaka M, Akimoto M, Palumbo J, Sakata T. A double-blind, parallel-group, placebo-controlled, 24-week, exploratory study of edaravone (MCI-186) for the treatment of advanced amyotrophic lateral sclerosis (ALS). Neurology 2016, 86(16 Supl): P3. 191.
Google Scholar
[7]
Abe K, Itoyama Y, Sobue G, et al. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener 2014, 15(7/8): 610-617.
DOI Google Scholar
[8]
Al-Chalabi A, Brown RH Jr. Finding a treatment for ALS - will gene editing cut it? N Engl J Med 2018, 378(15): 1454-1456.
DOI Google Scholar
[9]
Moura MC, Novaes MRCG, Zago YSSP, et al. Efficacy of stem cell therapy in amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Clin Med Res 2016, 8(4): 317-324.
DOI Google Scholar
[10]
Beers DR, Zhao WH, Liao B, et al. Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice. Brain Behav Immun 2011, 25(5): 1025-1035.
DOI Google Scholar
[11]
Rizzo F, Riboldi G, Salani S, et al. Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis. Cell Mol Life Sci 2014, 71(6): 999-1015.
DOI Google Scholar
[12]
Blanquer M, Pérez Espejo MA, Iniesta F, et al. Bone marrow stem cell transplantation in amyotrophic lateral sclerosis: technical aspects and preliminary results from a clinical trial. Methods Find Exp Clin Pharmacol 2010, 32(Suppl A): 31-37.
Google Scholar
[13]
Blanquer M, Moraleda JM, Iniesta F, et al. Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study. Stem Cells 2012, 30(6): 1277-1285.
DOI Google Scholar
[14]
Prabhakar S, Marwaha N, Lal V, et al. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study. Neurol India 2012, 60(5): 465-469.
DOI Google Scholar
[15]
Sharma AK, Sane HM, Paranjape AA, et al. The effect of autologous bone marrow mononuclear cell transplantation on the survival duration in amyotrophic lateral sclerosis - a retrospective controlled study. Am J Stem Cells 2015, 4(1): 50-65.
Google Scholar
[16]
General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent 2014, 81(3): 14-18.
DOI Google Scholar
[17]
Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 2002, 87(2): 589-598.
DOI Google Scholar
[18]
Zmuda JM, Cauley JA, Kriska A, et al. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997, 146(8): 609-617.
DOI Google Scholar
[19]
Longinetti E, Fang F. Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr Opin Neurol 2019, 32(5): 771-776.
DOI Google Scholar
[20]
Pupillo E, Messina P, Logroscino G, et al. Long-term survival in amyotrophic lateral sclerosis: a population-based study. Ann Neurol 2014, 75(2): 287-297.
DOI Google Scholar
[21]
Chio A, Logroscino G, Hardiman O, et al. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler 2009, 10(5-6): 310-323.
DOI Google Scholar
[22]
Testa D, Lovati R, Ferrarini M, et al. Survival of 793 patients with amyotrophic lateral sclerosis diagnosed over a 28-year period. Amyotroph Lateral Scler Other Motor Neuron Disord 2004, 5(4): 208-212.
DOI Google Scholar
[23]
del Aguila MA, Longstreth WT Jr, McGuire V, et al. Prognosis in amyotrophic lateral sclerosis: a population-based study. Neurology 2003, 60(5): 813-819.
DOI Google Scholar
[24]
Tysnes OB, Vollset SE, Aarli JA. Epidemiology of amyotrophic lateral sclerosis in Hordaland County, western Norway. Acta Neurol Scand 1991, 83(5): 280-285.
DOI Google Scholar
[25]
Chiò A, Logroscino G, Traynor BJ, et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 2013, 41(2): 118-130.
DOI Google Scholar
[26]
Manjaly ZR, Scott KM, Abhinav K, et al. The sex ratio in amyotrophic lateral sclerosis: A population based study. Amyotroph Lateral Scler 2010, 11(5): 439-442.
DOI Google Scholar
[27]
Gutiérrez-Lobos K, Scherer M, Anderer P, et al. The influence of age on the female/male ratio of treated incidence rates in depression. BMC Psychiatry 2002, 2: 3.
DOI Google Scholar
[28]
Sane H, Sharma A, Paranjape A, et al. Autologous bone marrow mononuclear cell intrathecal transplantation may affect the survival duration in amyotrophic lateral sclerosis-Clinical study. In Theme 14, Therapeutic Strategies, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Orlando, USA: Taylor & Francis Online, 2015, pp. 227-249.
DOI
[29]
Nakamizo T, Urushitani M, Inoue R, et al. Protection of cultured spinal motor neurons by estradiol. Neuroreport 2000, 11(16): 3493-3497.
DOI Google Scholar
[30]
Groeneveld GJ, Van Muiswinkel FL, Sturkenboom JM, et al. Ovariectomy and 17beta-estradiol modulate disease progression of a mouse model of ALS. Brain Res 2004, 1021(1): 128-131.
DOI Google Scholar
[31]
Monachelli GG, Meyer M, Rodríguez GE, et al. Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors. Acta Neurol Scand 2011, 123(1): 60-67.
DOI Google Scholar
[32]
Gonzalez Deniselle MC, López-Costa JJ, Saavedra JP, et al. Progesterone neuroprotection in the Wobbler mouse, a genetic model of spinal cord motor neuron disease. Neurobiol Dis 2002, 11(3): 457-468.
DOI Google Scholar
[33]
Gonzalez Deniselle MC, Garay L, Gonzalez S, et al. Progesterone modulates brain-derived neurotrophic factor and choline acetyltransferase in degenerating Wobbler motoneurons. Exp Neurol 2007, 203(2): 406-414.
DOI Google Scholar
[34]
Chió A, Meineri P, Tribolo A, et al. Risk factors in motor neuron disease: a case-control study. Neuroepidemiology 1991, 10(4): 174-184.
DOI Google Scholar
[35]
Popat RA, van den Eeden SK, Tanner CM, et al. Effect of reproductive factors and postmenopausal hormone use on the risk of amyotrophic lateral sclerosis. Neuroepidemiology 2006, 27(3): 117-121.
DOI Google Scholar
[36]
Gonzalez Deniselle MC, Liere P, Pianos A, et al. Steroid profiling in male wobbler mouse, a model of amyotrophic lateral sclerosis. Endocrinology 2016, 157(11): 4446-4460.
DOI Google Scholar
[37]
McLeod VM, Lau CL, Chiam MDF, et al. Androgen receptor antagonism accelerates disease onset in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Br J Pharmacol 2019, 176(13): 2111-2130.
DOI Google Scholar
[38]
Sane H, Paranjape A, Nivins S. Correlation of testosterone levels with progression of amyotrophic lateral sclerosis: a cross section study. 2017
DOI
[39]
Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993, 362(6415): 59-62.
DOI Google Scholar
[40]
Boillée S, Vande Velde C, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 2006, 52(1): 39-59.
DOI Google Scholar
[41]
Appel SH, Beers DR, Henkel JS. T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening? Trends Immunol 2010, 31(1): 7-17.
DOI Google Scholar
[42]
Zhao WH, Xie WJ, Le WD, et al. Activated microglia initiate motor neuron injury by a nitric oxide and glutamate-mediated mechanism. J Neuropathol Exp Neurol 2004, 63(9): 964-977.
DOI Google Scholar
[43]
Burguillos MA, Deierborg T, Kavanagh E, et al. Caspase signalling controls microglia activation and neurotoxicity. Nature 2011, 472(7343): 319-324.
DOI Google Scholar
[44]
Ghoshal A, Das S, Ghosh S, et al. Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis. Glia 2007, 55(5): 483-496.
DOI Google Scholar
[45]
Zhao WH, Beers DR, Appel SH. Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J Neuroimmune Pharmacol 2013, 8(4): 888-899.
DOI Google Scholar
[46]
Neher JJ, Neniskyte U, Zhao JW, et al. Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. J Immunol 2011, 186(8): 4973-4983.
DOI Google Scholar
[47]
Norden DM, Godbout JP. Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol 2013, 39(1): 19-34.
DOI Google Scholar
[48]
Hu XM, Leak RK, Shi YJ, et al. Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol 2015, 11(1): 56-64.
DOI Google Scholar
[49]
Dupuis L, Dengler R, Heneka MT, et al. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One 2012, 7(6): e37885.
DOI Google Scholar
[50]
Smith SA, Miller RG, Murphy JR, et al. Treatment of ALS with high dose pulse cyclophosphamide. J Neurol Sci 1994, 124(Suppl): 84-87.
DOI Google Scholar
[51]
Brown RH Jr, Hauser SL, Harrington H, et al. Failure of immunosuppression with a 10- to 14-day course of high-dose intravenous cyclophosphamide to alter the progression of amyotrophic lateral sclerosis. Arch Neurol 1986, 43(4): 383-384.
DOI Google Scholar
[52]
Cudkowicz ME, Shefner JM, Schoenfeld DA, et al. Trial of celecoxib in amyotrophic lateral sclerosis. Ann Neurol 2006, 60(1): 22-31.
DOI Google Scholar
[53]
Stommel EW, Cohen JA, Fadul CE, et al. Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial. Amyotroph Lateral Scler 2009, 10(5/6): 393-404.
DOI Google Scholar
[54]
Gordon PH, Moore DH, Miller RG, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol 2007, 6(12): 1045-1053.
DOI Google Scholar
[55]
Levine TD, Bowser R, Hank NC, et al. A pilot trial of pioglitazone HCl and tretinoin in ALS: cerebrospinal fluid biomarkers to monitor drug efficacy and predict rate of disease progression. Neurol Res Int 2012, 2012: 582075.
DOI Google Scholar
[56]
Xie J, March KL, Murphy MP. Bone marrow-derived cells: from the laboratory to the clinic. In Regenerative Medicine for Peripheral Artery Disease. Mohler ER, III, Annex BH, Eds. Amsterdam: Elsevier, 2016, pp. 27-42.
DOI
[57]
Challen GA, Little MH. A side order of stem cells: the SP phenotype. Stem Cells 2006, 24(1): 3-12.
DOI Google Scholar
[58]
Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 2010, 28(3): 585-596.
DOI Google Scholar
[59]
Kucia MJ, Wysoczynski M, Wu W, et al. Evidence that very small embryonic-like stem cells are mobilized into peripheral blood. Stem Cells 2008, 26(8): 2083-2092.
DOI Google Scholar
[60]
Ji KH, Xiong J, Hu KM, et al. Simultaneous expression of Oct4 and genes of three germ layers in single cell-derived multipotent adult progenitor cells. Ann Hematol 2008, 87(6): 431-438.
DOI Google Scholar
[61]
Park C, Ma YD, Choi K. Evidence for the hemangioblast. Exp Hematol 2005, 33(9): 965-970.
DOI Google Scholar
[62]
Kucia M, Reca R, Jala VR, et al. Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells. Leukemia 2005, 19(7): 1118-1127.
DOI Google Scholar
[63]
Yang B, Parsha K, Schaar K, et al. Various cell populations within the mononuclear fraction of bone marrow contribute to the beneficial effects of autologous bone marrow cell therapy in a rodent stroke model. Transl Stroke Res 2016, 7(4): 322-330.
DOI Google Scholar
[64]
Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol 2009, 37(12): 1445-1453.
DOI Google Scholar
[65]
Hegyi B, Környei Z, Ferenczi S, et al. Regulation of mouse microglia activation and effector functions by bone marrow-derived mesenchymal stem cells. Stem Cells Dev 2014, 23(21): 2600-2612.
DOI Google Scholar
[66]
Liu J, Hjorth E, Zhu M, et al. Interplay between human microglia and neural stem/progenitor cells in an allogeneic co-culture model. J Cell Mol Med 2013, 17(11): 1434-1443.
DOI Google Scholar
[67]
Yan K, Zhang R, Sun CM, et al. Bone marrow-derived mesenchymal stem cells maintain the resting phenotype of microglia and inhibit microglial activation. PLoS One 2013, 8(12): e84116.
DOI Google Scholar
[68]
Pastor D, Viso-León MC, Jones J, et al. Comparative effects between bone marrow and mesenchymal stem cell transplantation in GDNF expression and motor function recovery in a motorneuron degenerative mouse model. Stem Cell Rev Rep 2012, 8(2): 445-458.
DOI Google Scholar
[69]
Labouyrie E, Dubus P, Groppi A, et al. Expression of neurotrophins and their receptors in human bone marrow. Am J Pathol 1999, 154(2): 405-415.
DOI Google Scholar
[70]
Jones J, Jaramillo-Merchán J, Bueno C, et al. Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar Ataxia. Neurobiol Dis 2010, 40(2): 415-423.
DOI Google Scholar
[71]
Auffray I, Chevalier S, Froger J, et al. Nerve growth factor is involved in the supportive effect by bone marrow-derived stromal cells of the factor-dependent human cell line UT-7. Blood 1996, 88(5): 1608-18.
DOI Google Scholar
[72]
Wang YM, Mao XO, Xie L, et al. Vascular endothelial growth factor overexpression delays neurodegeneration and prolongs survival in amyotrophic lateral sclerosis mice. J Neurosci 2007, 27(2): 304-307.
DOI Google Scholar
[73]
Cabanes C, Bonilla S, Tabares L, et al. Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration. Neurobiol Dis 2007, 26(2): 408-418.
DOI Google Scholar
[74]
Suzuki M, McHugh J, Tork C, et al. GDNF secreting human neural progenitor cells protect dying motor neurons, but not their projection to muscle, in a rat model of familial ALS. PLoS One 2007, 2(8): e689.
DOI Google Scholar
[75]
Wang JP, Fu XJ, Jiang C, et al. Bone marrow mononuclear cell transplantation promotes therapeutic angiogenesis via upregulation of the VEGF-VEGFR2 signaling pathway in a rat model of vascular dementia. Behav Brain Res 2014, 265: 171-180.
DOI Google Scholar
[76]
Oosthuyse B, Moons L, Storkebaum E, et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 2001, 28(2): 131-138.
DOI Google Scholar
[77]
Jin KL, Mao XO, Greenberg DA. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci USA 2000, 97(18): 10242-10247.
DOI Google Scholar
[78]
Jin KL, Mao XO, Nagayama T, et al. Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3'-kinase/Akt signaling by global cerebral ischemia in the rat. Neuroscience 2000, 100(4): 713-717.
DOI Google Scholar
[79]
Silverman WF, Krum JM, Mani N, et al. Vascular, glial and neuronal effects of vascular endothelial growth factor in mesencephalic explant cultures. Neuroscience 1999, 90(4): 1529-1541.
DOI Google Scholar
[80]
Carmeliet P, de Almodovar CR. VEGF ligands and receptors: implications in neurodevelopment and neurodegeneration. Cell Mol Life Sci 2013, 70(10): 1763-1778.
DOI Google Scholar
[81]
Ruiz de Almodovar C, Lambrechts D, Mazzone M, et al. Role and therapeutic potential of VEGF in the nervous system. Physiol Rev 2009, 89(2): 607-648.
DOI Google Scholar
[82]
Azzouz M, Ralph GS, Storkebaum E, et al. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 2004, 429(6990): 413-417.
DOI Google Scholar
[83]
Storkebaum E, Lambrechts D, Dewerchin M, et al. Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS. Nat Neurosci 2005, 8(1): 85-92.
DOI Google Scholar
[84]
Zheng CY, Nennesmo I, Fadeel B, et al. Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS. Ann Neurol 2004, 56(4): 564-567.
DOI Google Scholar
[85]
Feng HL, Leng Y, Ma CH, et al. Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model. Neuroscience 2008, 155(3): 567-572.
DOI Google Scholar
[86]
Chen RW, Chuang DM. Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem 1999, 274(10): 6039-6042.
DOI Google Scholar
[87]
Shalbuyeva N, Brustovetsky T, Brustovetsky N. Lithium desensitizes brain mitochondria to calcium, antagonizes permeability transition, and diminishes cytochrome C release. J Biol Chem 2007, 282(25): 18057-18068.
DOI Google Scholar
[88]
Bachmann RF, Wang Y, Yuan PX, et al. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage. Int J Neuropsychopharmacol 2009, 12(6): 805-822.
DOI Google Scholar
[89]
Quiroz JA, Machado-Vieira R, Zarate CA Jr, et al. Novel insights into lithium's mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology 2010, 62(1): 50-60.
DOI Google Scholar
[90]
Bosche B, Schäfer M, Graf R, et al. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells. Biochem Biophys Res Commun 2013, 434(2): 268-272.
DOI Google Scholar
[91]
Ngok-Ngam P, Watcharasit P, Thiantanawat A, et al. Pharmacological inhibition of GSK3 attenuates DNA damage-induced apoptosis via reduction of p53 mitochondrial translocation and Bax oligomerization in neuroblastoma SH-SY5Y cells. Cell Mol Biol Lett 2013, 18(1): 58-74.
DOI Google Scholar
[92]
Feier G, Valvassori SS, Varela RB, et al. Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine. Pharmacol Biochem Behav 2013, 103(3): 589-596.
DOI Google Scholar
[93]
Busceti CL, Biagioni F, Riozzi B, et al. Enhanced tau phosphorylation in the hippocampus of mice treated with 3,4-methylenedioxymethamphetamine (“Ecstasy”). J Neurosci 2008, 28(12): 3234-3245.
DOI Google Scholar
[94]
Fornai F, Longone P, Cafaro L, et al. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2008, 105(6): 2052-2057.
DOI Google Scholar
[95]
Harris VK, Yan QJ, Vyshkina T, et al. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci 2012, 313(1/2): 167-177.
DOI Google Scholar
[96]
Wu SF, Suzuki Y, Kitada M, et al. New method for transplantation of neurosphere cells into injured spinal cord through cerebrospinal fluid in rat. Neurosci Lett 2002, 318(2): 81-84.
DOI Google Scholar
[97]
Bai HL, Suzuki Y, Noda T, et al. Dissemination and proliferation of neural stem cells on the spinal cord by injection into the fourth ventricle of the rat: a method for cell transplantation. J Neurosci Methods 2003, 124(2): 181-187.
DOI Google Scholar
[98]
Fischer UM, Harting MT, Jimenez F, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev 2009, 18(5): 683-692.
DOI Google Scholar
[99]
Vasconcelos-dos-Santos A, Rosado-de-Castro PH, Lopes de Souza SA, et al. Intravenous and intra-arterial administration of bone marrow mononuclear cells after focal cerebral ischemia: Is there a difference in biodistribution and efficacy? Stem Cell Res 2012, 9(1): 1-8.
DOI Google Scholar
[100]
Sadan O, Melamed E, Offen D. Bone-marrow-derived mesenchymal stem cell therapy for neurodegenerative diseases. Expert Opin Biol Ther 2009, 9(12): 1487-1497.
DOI Google Scholar
[101]
Pastor D, Viso-León MC, Botella-López A, et al. Bone marrow transplantation in hindlimb muscles of motoneuron degenerative mice reduces neuronal death and improves motor function. Stem Cells Dev 2013, 22(11): 1633-1644.
DOI Google Scholar
[102]
Corti S, Locatelli F, Donadoni C, et al. Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and contribute to CNS, heart and skeletal muscle tissues. Brain 2004, 127(Pt 11): 2518-2532.
DOI Google Scholar
[103]
Gubert F, Bonacossa-Pereira I, Decotelli AB, et al. Bone-marrow mononuclear cell therapy in a mouse model of amyotrophic lateral sclerosis: Functional outcomes from different administration routes. Brain Res 2019, 1712: 73-81.
DOI Google Scholar
[104]
Gubert F, Decotelli AB, Bonacossa-Pereira I, et al. Intraspinal bone-marrow cell therapy at pre- and symptomatic phases in a mouse model of amyotrophic lateral sclerosis. Stem Cell Res Ther 2016, 7: 41.
DOI Google Scholar
[105]
R. Martinez H, Gómez-Almaguer D, Jaime-Pérez JC, et al. Intrathecal delivery of bone marrow stem cells in ALS: A preliminary report. Trends in Transplant, 2017 10(1): 1-6.
DOI Google Scholar
[106]
Deda H, Inci MC, Kürekçi AE, et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy 2009, 11(1): 18-25.
DOI Google Scholar
[107]
Ruiz-López FJ, Guardiola J, Izura V, et al. Breathing pattern in a phase I clinical trial of intraspinal injection of autologous bone marrow mononuclear cells in patients with amyotrophic lateral sclerosis. Respir Physiol Neurobiol 2016, 221: 54-58.
Google Scholar
Publication history
Copyright
Rights and permissions

Publication history

Received: 24 May 2021
Accepted: 25 June 2021
Published: 05 June 2021
Issue date: June 2021

Copyright

© The authors 2021

Rights and permissions

This article is published with open access at http://jnr.tsinghuajournals.com

Return