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Journal of Neurorestoratology 2017, 5(1): 5-19 https://doi.org/10.2147/JN.S99304
Review | Open Access | Issue | Published: 09 January 2017

Stem cell-transplantation therapy for adrenoleukodystrophy: current perspectives

Show Author's Information Weston Miller( )
Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA
Keywords:
adrenoleukodystrophy, cerebral adrenoleukodystrophy, stem cell transplantation, bone marrow transplantation, umbilical cord-blood transplantation, hematopoietic cell transplantation
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Miller W. Stem cell-transplantation therapy for adrenoleukodystrophy: current perspectives. Journal of Neurorestoratology, 2017, 5(1): 5-19. https://doi.org/10.2147/JN.S99304
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Abstract Full text About this article

Adrenoleukodystrophy (ALD) is a rare, X-linked peroxisomal disorder of impaired very long-chain fatty-acid metabolism. It results from various mutations in the ABCD1 gene (Xq28). All males with the biochemical defect of ALD are at risk of developing cerebral white-matter disease (cALD) during their lifetime. Thirty-five percent of ALD patients develop cALD in boyhood, a life-threatening phenotype characterized by rapidly expanding, neuroinflammatory demyelination and irreversible clinical neurologic decline. The ABCD1 genotype does not predict susceptibility to or protection from the childhood cALD phenotype; therefore, clinicians must remain ever vigilant for its development when monitoring ALD patients. Currently, allogeneic hematopoietic cell transplantation (HCT) is the standard of care for boyhood cALD. While HCT provides dramatic functional survival benefit in boys with early, presymptomatic cALD, outcomes are less favorable and less predictable for those with more advanced disease. Furthermore, little is known about how successful HCT in childhood might impact the onset of central nervous system disease in adulthood. Finally, investigations of experimental gene-therapy strategies are ongoing. This review explores current perspectives of stem cell transplantation in cALD.


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About this article

Stem cell-transplantation therapy for adrenoleukodystrophy: current perspectives

Show Author's information Weston Miller( )
Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA

Abstract

Adrenoleukodystrophy (ALD) is a rare, X-linked peroxisomal disorder of impaired very long-chain fatty-acid metabolism. It results from various mutations in the ABCD1 gene (Xq28). All males with the biochemical defect of ALD are at risk of developing cerebral white-matter disease (cALD) during their lifetime. Thirty-five percent of ALD patients develop cALD in boyhood, a life-threatening phenotype characterized by rapidly expanding, neuroinflammatory demyelination and irreversible clinical neurologic decline. The ABCD1 genotype does not predict susceptibility to or protection from the childhood cALD phenotype; therefore, clinicians must remain ever vigilant for its development when monitoring ALD patients. Currently, allogeneic hematopoietic cell transplantation (HCT) is the standard of care for boyhood cALD. While HCT provides dramatic functional survival benefit in boys with early, presymptomatic cALD, outcomes are less favorable and less predictable for those with more advanced disease. Furthermore, little is known about how successful HCT in childhood might impact the onset of central nervous system disease in adulthood. Finally, investigations of experimental gene-therapy strategies are ongoing. This review explores current perspectives of stem cell transplantation in cALD.

Keywords: adrenoleukodystrophy, cerebral adrenoleukodystrophy, stem cell transplantation, bone marrow transplantation, umbilical cord-blood transplantation, hematopoietic cell transplantation

References(93)

1.
Bezman L, Moser A, Raymond G, et al. Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. 2001;49(4):512-517.
DOI Google Scholar
2.
Academic Medical Center, Amsterdam. Adrenoleukodystrophy database. 2016. Available from: http://www.x-ald.nl. Accessed September 30, 2016.
3.
Moser H. Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain. 1997;120(Pt 8):1485-1508.
DOI Google Scholar
4.
Engelen M, Kemp S, de Visser M, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7:51.
DOI Google Scholar
5.
Wanders R, Vreken P, Ferdinandusse S, et al. Peroxisomal fatty acid α- and β-oxidation in humans: enzymology, peroxisomal metabolite transporters and peroxisomal diseases. Biochem Soc Trans. 2001;29(Pt 2):250-267.
DOI Google Scholar
6.
Igarashi M, Schaumburg HH, Powers J, Kishmoto Y, Kolodny E, Suzuki K. Fatty acid abnormality in adrenoleukodystrophy. J Neurochem. 1976;26(4):851-860.
DOI Google Scholar
7.
Moser AB, Kreiter N, Bezman L, et al. Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol. 1999;45(1):100-110.
DOI
8.
Berger J, Gärtner J. X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects. Biochim Biophys Acta. 2006;1763(12):1721-1732.
DOI Google Scholar
9.
Berger J, Molzer B, Faé I, Bernheimer H. X-linked adrenoleukodystrophy (ALD): a novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes. Biochem Biophys Res Commun. 1994;205(3):1638-1643.
DOI Google Scholar
10.
Moser H, Dubey P, Fatemi A. Progress in X-linked adrenoleukodystrophy. Curr Opin Neurol. 2004;17(3):263-269.
DOI Google Scholar
11.
Mahmood A, Dubey P, Moser H, Moser A. X-linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes. Pediatr Transplant. 2005;9 Suppl 7:55-62.
DOI Google Scholar
12.
Kim J, Kim H. Childhood X-linked adrenoleukodystrophy: clinical-pathologic overview and MR imaging manifestations at initial evaluation and follow-up. Radiographics. 2005;25(3):619-631.
DOI Google Scholar
13.
Loes DJ, Fatemi A, Melhem ER, et al. Analysis of MRI patterns aids prediction of progression in X-linked adrenoleukodystrophy. Neurology. 2003;61(3):369-374.
DOI Google Scholar
14.
Hobbs JR, Hugh-Jones K, Barrett AJ, et al. Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet. 1981;2(8249):709-712.
DOI Google Scholar
15.
Pridjian G, Humbert J, Willis J, Shapira E. Presymptomatic late-infantile metachromatic leukodystrophy treated with bone marrow transplantation. J Pediatr. 1994;125(5):755-758.
DOI Google Scholar
16.
Fratantoni JC, Hall CW, Neufeld EF. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science. 1968;162(853):570-572.
DOI Google Scholar
17.
Berger J, Forss-Petter S, Eichler FS. Pathophysiology of X-linked adrenoleukodystrophy. Biochimie. 2014;98:135-142.
DOI Google Scholar
18.
Ferrer I, Aubourg P, Pujol A. General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain Pathol. 2010;20(4):817-830.
DOI Google Scholar
19.
Vargas CR, Wajner M, Sirtori LR, et al. Evidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy. Biochim Biophys Acta. 2004;1688(1):26-32.
DOI Google Scholar
20.
Deon M, Sitta A, Barschak AG, et al. Induction of lipid peroxidation and decrease of antioxidant defenses in symptomatic and asymptomatic patients with X-linked adrenoleukodystrophy. Int J Dev Neurosci. 2007;25(7):441-444.
DOI Google Scholar
21.
Powers JM, Pei Z, Heinzer AK, et al. Adreno-leukodystrophy: oxidative stress of mice and men. J Neuropathol Exp Neurol. 2005;64(12):1067-1079.
DOI Google Scholar
22.
Rockenbach FJ, Deon M, Marchese DP, et al. The effect of bone marrow transplantation on oxidative stress in X-linked adrenoleukodystrophy. Mol Genet Metab. 2012;106(2):231-236.
DOI Google Scholar
23.
Yamada T, Ohyagi Y, Shinnoh N, et al. Therapeutic effects of normal cells on ABCD1 deficient cells in vitro and hematopoietic cell transplantation in the X-ALD mouse model. J Neurol Sci. 2004;218(1-2):91-97.
DOI Google Scholar
24.
Moser HW, Tutschka PJ, Brown FR, et al. Bone marrow transplant in adrenoleukodystrophy. Neurology. 1984;34(11):1410-1417.
DOI Google Scholar
25.
Aubourg P, Blanche S, Jambaqué I, et al. Reversal of early neurologic and neuroradiologic manifestations of X-linked adrenoleukodystrophy by bone marrow transplantation. N Engl J Med. 1990;322(26):1860-1866.
DOI Google Scholar
26.
Loes D, Hite S, Moser H, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol. 1994;15(9):1761-1766.
Google Scholar
27.
Loes DJ, Stillman AE, Hite S, et al. Childhood cerebral form of adrenoleukodystrophy: short-term effect of bone marrow transplantation on brain MR observations. AJNR Am J Neuroradiol. 1994;15(9):1767-1771.
Google Scholar
28.
Malm G, Ringdén O, Anvret M, et al. Treatment of adrenoleukodystrophy with bone marrow transplantation. Acta Paediatr. 1997;86(5):484-492.
DOI Google Scholar
29.
Nowaczyk MJ, Saunders EF, Tein I, Blaser SI, Clarke JT. Immunoablation does not delay the neurologic progression of X-linked adrenoleukodystrophy. J Pediatr. 1997;131(3):453-455.
DOI Google Scholar
30.
Kapelushnik J, Varadi G, Nagler A. Matched unrelated human umbilical cord blood transplantation for X-linked adrenoleukodystrophy. J Pediatr Hematol Oncol. 1998;20(3):257-259.
DOI Google Scholar
31.
Lin HC, Lin KH, Wang PJ. Transplantation for adrenoleukodystrophy with HLA-A and B nonidentical paternal marrow: report of one case. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1998;39(4):260-263.
Google Scholar
32.
Shapiro E, Krivit W, Lockman L, et al. Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet. 2000;356(9231):713-718.
DOI Google Scholar
33.
Baumann M, Korenke GC, Weddige-Diedrichs A, et al. Haematopoietic stem cell transplantation in 12 patients with cerebral X-linked adrenoleukodystrophy. Eur J Pediatr. 2003;162(1):6-14.
DOI Google Scholar
34.
Wilken B, Dechent P, Brockmann K, et al. Quantitative proton magnetic resonance spectroscopy of children with adrenoleukodystrophy before and after hematopoietic stem cell transplantation. Neuropediatrics. 2003;34(5):237-246.
DOI Google Scholar
35.
Peters C, Charnas LR, Tan Y, et al. Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood. 2004;104(3):881-888.
DOI Google Scholar
36.
Beam D, Poe M, Provenzale J, et al. Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy. Biol Blood Marrow Transplant. 2007;13(6):665-674.
DOI Google Scholar
37.
Gess A, Christiansen SP, Pond D, Peters C. Predictive factors for vision loss after hematopoietic cell transplant for X-linked adrenoleukodystrophy. J AAPOS. 2008;12(3):273-276.
DOI Google Scholar
38.
Miller WP, Rothman SM, Nascene D, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971-1978.
DOI Google Scholar
39.
Mahmood A, Raymond G, Dubey P, Peters C, Moser H. Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: a comparison study. Lancet Neurol. 2007;6(8):687-692.
DOI Google Scholar
40.
Tolar J, Orchard PJ, Bjoraker KJ, Ziegler RS, Shapiro EG, Charnas L. N-acetyl-L-cysteine improves outcome of advanced cerebral adrenoleukodystrophy. Bone Marrow Transplant. 2007;39(4):211-215.
DOI Google Scholar
41.
Awaya T, Kato T, Niwa A, et al. Successful cord blood transplantation using a reduced-intensity conditioning regimen for advanced childhood-onset cerebral adrenoleukodystrophy. Pediatr Transplant. 2011;15(6):E116-E120.
Google Scholar
42.
Niizuma H, Uematsu M, Sakamoto O, et al. Successful cord blood transplantation with reduced-intensity conditioning for childhood cerebral X-linked adrenoleukodystrophy at advanced and early stages. Pediatr Transplant. 2012;16(2):E63-E70.
DOI Google Scholar
43.
Resnick I, Hai AA, Shapira M, et al. Treatment of X-linked childhood cerebral adrenoleukodystrophy by the use of an allogeneic stem cell transplantation with reduced intensity conditioning regimen. Clin Transplant. 2005;19(6):840-847.
DOI Google Scholar
44.
Fernandes J, Bonfim C, Kerbauy F, et al. T-cell-replete haploidentical stem cell transplantation with post-transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: an immediate choice for an urgent situation. Biol Blood Marrow Transplant. 2014;20(2 Suppl):S168-S169.
DOI Google Scholar
45.
Capotondo A, Milazzo R, Politi LS, et al. Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc Natl Acad Sci U S A. 2012;109(37):15018-15023.
DOI Google Scholar
46.
Wilkinson FL, Sergijenko A, Langford-Smith KJ, Malinowska M, Wynn RF, Bigger BW. Busulfan conditioning enhances engraftment of hematopoietic donor-derived cells in the brain compared with irradiation. Mol Ther. 2013;21(4):868-876.
DOI Google Scholar
47.
Miller WP, Rothman SM, Nascene D, et al. Outcomes following allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971-1978.
DOI Google Scholar
48.
Orchard PJ, Lund T, Miller W, et al. Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy. J Neuroinflammation. 2011;8:144.
DOI Google Scholar
49.
Miller WP, Mantovani LF, Muzic J, et al. Intensity of MRI gadolinium enhancement in cerebral adrenoleukodystrophy: a biomarker for inflammation and predictor of outcome following transplantation in higher risk patients. AJNR Am J Neuroradiol. 2016;37(2):367-372.
DOI Google Scholar
50.
Gassas A, Raiman J, White L, Schechter T, Clarke J, Doyle J. Long-term adaptive functioning outcomes of children with inherited metabolic and genetic diseases treated with hematopoietic stem cell transplantation in a single large pediatric center: parents’ perspective. J Pediatr Hematol Oncol. 2011;33(3):216-220.
DOI Google Scholar
51.
van Geel BM, Poll-The BT, Verrips A, Boelens JJ, Kemp S, Engelen M. Hematopoietic cell transplantation does not prevent myelopathy in X-linked adrenoleukodystrophy: a retrospective study. J Inherit Metab Dis. 2015;38(2):359-361.
DOI Google Scholar
52.
Petryk A, Polgreen LE, Chahla S, Miller W, Orchard PJ. No evidence for the reversal of adrenal failure after hematopoietic cell transplantation in X-linked adrenoleukodystrophy. Bone Marrow Transplant. 2012;47(10):1377-1378.
DOI Google Scholar
53.
Horn MA, Erichsen MM, Wolff AS, et al. Screening for X-linked adrenoleukodystrophy among adult men with Addison’s disease. Clin Endocrinol (Oxf). 2013;79(3):316-320.
DOI Google Scholar
54.
Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison’s disease in young adult male patients. J Clin Endocrinol Metab. 1996;81(2):470-474.
DOI Google Scholar
55.
Polgreen LE, Chahla S, Miller W, et al. Early diagnosis of cerebral X-linked adrenoleukodystrophy in boys with Addison’s disease improves survival and neurological outcomes. Eur J Pediatr. 2011;170(8):1049-1054.
DOI Google Scholar
56.
Raymond G, Jones R, Moser A. Newborn screening for adrenoleukodystrophy: implications for therapy. Mol Diagn Ther. 2007;11(6):381-384.
DOI Google Scholar
57.
Kemper AR, Brosco J, Comeau AM, et al. Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation. Genet Med. Epub 2016 Jun 23.
Google Scholar
58.
Oz G, Tkáč I, Charnas LR, et al. Assessment of adrenoleukodystrophy lesions by high field MRS in non-sedated pediatric patients. Neurology. 2005;64(3):434-441.
DOI Google Scholar
59.
Musolino PL, Rapalino O, Caruso P, Caviness VS, Eichler FS. Hypoperfusion predicts lesion progression in cerebral X-linked adrenoleukodystrophy. Brain. 2012;135(Pt 9):2676-2683.
DOI Google Scholar
60.
Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015;125(13):2164-2172.
DOI Google Scholar
61.
Kahraman S, Beyazyurek C, Yesilipek MA, et al. Successful haematopoietic stem cell transplantation in 44 children from healthy siblings conceived after preimplantation HLA matching. Reprod Biomed Online. 2014;29(3):340-351.
DOI Google Scholar
62.
Bartelink IH, van Reij EM, Gerhardt CE, et al. Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Biol Blood Marrow Transplant. 2014;20(3):345-353.
DOI Google Scholar
63.
Hitomi T, Mezaki T, Tomimoto H, et al. Long-term effect of bone marrow transplantation in adult-onset adrenoleukodystrophy. Eur J Neurol. 2005;12(10):807-810.
DOI Google Scholar
64.
Fitzpatrick AS, Loughrey CM, Johnston P, et al. Haematopoietic stem-cell transplant for adult cerebral adrenoleukodystrophy. Eur J Neurol. 2008;15(3):e21-e22.
DOI Google Scholar
65.
Benhamida S, Pflumio F, Dubart-Kupperschmitt A, et al. Transduced CD34+ cells from adrenoleukodystrophy patients with HIV-derived vector mediate long-term engraftment of NOD/SCID mice. Mol Ther. 2003;7(3):317-324.
DOI Google Scholar
66.
Doerflinger N, Miclea JM, Lopez J, et al. Retroviral transfer and long-term expression of the adrenoleukodystrophy gene in human CD34+ cells. Hum Gene Ther. 1998;9(7):1025-1036.
DOI Google Scholar
67.
Cartier N, Hacein-Bey-Abina S, Bartholomae C, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science. 2009;326(5954):818-823.
DOI Google Scholar
68.
Cartier N, Lopez J, Moullier P, et al. Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts. Proc Natl Acad Sci U S A. 1995;92(5):1674-1678.
DOI Google Scholar
69.
Eichler F, Duncan C, Thrasher A, et al. Interim results from a phase 2/3 study of the efficacy and safety of ex vivo gene therapy with lentiviral vector (Lenti-D) for childhood cerebral adrenoleukodystrophy. Neurology. 2016;86(16 Suppl):PL02.002.
DOI Google Scholar
70.
Gong Y, Mu D, Prabhakar S, et al. Adenoassociated virus serotype 9-mediated gene therapy for X-linked adrenoleukodystrophy. Mol Ther. 2015;23(5):824-834.
DOI Google Scholar
71.
Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726-736.
DOI Google Scholar
72.
Amado LC, Saliaris AP, Schuleri KH, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A. 2005;102(32):11474-11479.
DOI Google Scholar
73.
Kan I, Melamed E, Offen D. Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases. Handb Exp Pharmacol. 2007;(180):219-242.
DOI Google Scholar
74.
Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A. 1999;96(19):10711-10716.
DOI Google Scholar
75.
Mansilla E, Marin GH, Sturla F, et al. Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries. Transplant Proc. 2005;37(1):292-294.
DOI Google Scholar
76.
Miller RH, Bai L. Cellular approaches for stimulating CNS remyelination. Regen Med. 2007;2(5):817-829.
DOI Google Scholar
77.
Müller I, Kustermann-Kuhn B, Holzwarth C, et al. In vitro analysis of multipotent mesenchymal stromal cells as potential cellular therapeutics in neurometabolic diseases in pediatric patients. Exp Hematol. 2006;34(10):1413-1419.
DOI Google Scholar
78.
Prockop DJ, Azizi SA, Colter D, Digirolamo C, Kopen G, Phinney DG. Potential use of stem cells from bone marrow to repair the extracellular matrix and the central nervous system. Biochem Soc Trans. 2000;28(4):341-345.
DOI Google Scholar
79.
Chen X, Armstrong MA, Li G. Mesenchymal stem cells in immunoregulation. Immunol Cell Biol. 2006;84(5):413-421.
DOI Google Scholar
80.
Crop M, Baan C, Weimar W, Hoogduijn M. Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation. Transpl Int. 2009;22(4):365-376.
DOI Google Scholar
81.
Gordon D, Pavlovska G, Glover CP, Uney JB, Wraith D, Scolding NJ. Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration. Neurosci Lett. 2008;448(1):71-73.
DOI Google Scholar
82.
Iyer SS, Rojas M. Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies. Expert Opin Biol Ther. 2008;8(5):569-581.
DOI Google Scholar
83.
Nasef A, Ashammakhi N, Fouillard L. Immunomodulatory effect of mesenchymal stromal cells: possible mechanisms. Regen Med. 2008;3(4):531-546.
DOI Google Scholar
84.
Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110(10):3499-3506.
DOI Google Scholar
85.
Nowakowski A, Walczak P, Lukomska B, Janowski M. Genetic engineering of mesenchymal stem cells to induce their migration and survival. Stem Cells Int. 2016;2016:4956063.
DOI Google Scholar
86.
Park JS, Suryaprakash S, Lao YH, Leong KW. Engineering mesenchymal stem cells for regenerative medicine and drug delivery. Methods. 2015;84:3-16.
DOI Google Scholar
87.
Windrem MS, Schanz SJ, Guo M, et al. Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell. 2008;2(6):553-565.
DOI Google Scholar
88.
Duncan ID. Oligodendrocytes and stem cell transplantation: their potential in the treatment of leukoencephalopathies. J Inherit Metab Dis. 2005;28(3):357-368.
DOI Google Scholar
89.
Ricca A, Rufo N, Ungari S, et al. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy. Hum Mol Genet. 2015;24(12):3372-3389.
DOI Google Scholar
90.
Gupta N, Henry RG, Strober J, et al. Neural stem cell engraftment and myelination in the human brain. Sci Transl Med. 2012;4(155):155ra137.
DOI Google Scholar
91.
Osorio MJ, Goldman SA. Glial progenitor cell-based treatment of the childhood leukodystrophies. Exp Neurol. 2016;283(Pt B):476-488.
DOI Google Scholar
92.
Boyer-Di Ponio J, El-Ayoubi F, Glacial F, et al. Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes. PLoS One. 2014;9(1):e84179.
DOI Google Scholar
93.
Goldman SA. Stem and progenitor cell-based therapy of the central nervous system: hopes, hype, and wishful thinking. Cell Stem Cell. 2016;18(2):174-188.
DOI Google Scholar
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