|
 |
| REVIEW ARTICLE |
|
| Year : 2016 | Volume
: 2
| Issue : 3 | Page : 121-125 |
|
Clinical application of oligodendrocyte precursor cells for cell-based therapy
Naohiro Egawa1, Hajime Takase2, Lok Josephine3, Ryosuke Takahashi4, Ken Arai2
1 Department of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
2 Department of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, USA
3 Department of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School; Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
4 Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| Date of Submission | 23-Aug-2016 |
| Date of Decision | 24-Aug-2016 |
| Date of Acceptance | 25-Aug-2016 |
| Date of Web Publication | 18-Oct-2016 |
Correspondence Address:
Naohiro Egawa
Department of Neurology, Kyoto University Graduate School of Medicine, 54 Shogoin.Kawaharacho, Sakyoku, Kyoto 606-8507, Japan
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2394-8108.192515
Oligodendrocyte precursor cells (OPCs), which give rise to mature oligodendrocytes (OLs), play important roles in maintaining white matter function. Even during the adulthood period, OPCs comprise roughly 5% of all cells in the forebrain and retain a capability to become myelinated OLs. Recently, OPCs have been proposed as a novel source for cell-based therapy. For the purpose, OPCs can be obtained from embryonic stem cells, induced pluripotent stem cells, and directly converted cells derived from patients. Here, we will provide a brief review of the potential of using OPCs as a cell-based therapy for treating various neurological diseases. Keywords: Cell transplantation, oligodendrocyte precursor cells, stem cell therapy
How to cite this article:
Egawa N, Takase H, Josephine L, Takahashi R, Arai K. Clinical application of oligodendrocyte precursor cells for cell-based therapy. Brain Circ 2016;2:121-5 |
| Introduction | |  |
In 1983, morphologically and physiologically, distinct cells were purified as bipotential oligodendrocyte-type-2 astrocyte progenitor cells (O-2A cells), which were immunoreactive to A2B5 antibody.[1] Since the cells produced oligodendrocytes (OLs), they were called as oligodendrocyte precursor cells (OPCs). However, the original property of OPCs was not restricted to OLs, and the cells expressed NG2 chondroitin sulfate proteoglycan 4.[2] Therefore, the O-2A cells are now also referred as NG2 cells or polydendrocytes.[3] The existence of OPCs in central nervous system (CNS) has been widely recognized by utilizing of their immnunoreactivity to NG2 and the alpha receptor of platelet-derived growth factor (PDGF-Rα).[4] OPCs comprise 2%–8% of all cells in the human adult forebrain.[5],[6] Under some conditions, OPCs also produce astrocytes and neurons.[7] Therefore, OPCs may work as multipotent neuronal stem cells and could be a source for cell-based therapy for neurological diseases. In this mini-review, we will briefly introduce the key properties of OPCs and discuss the therapeutic potential of OPCs as a source for cell transplantation.
| Oligodendrocyte Precursor Cell Function in Central Nervous System | | |
OPCs are active in developing CNS, and their roles during the developing stage have been extensively examined in rodents. In spinal cord, OPCs first appear in ventral neural tube in the embryonic stage day 14.5 (rat) and day 12.5 (mouse). The region includes p3 domain defined by the expression of homeodomain transcriptional factor Nkx2.2 and pMN/OL domain defined by the expression of basic helix-loop-helix transcriptional factor Olig2.[8],[9],[10] OPCs in the ventral neural tube are consisting of about 80% of total OPCs in the whole spinal cord. A few days later, OPC is also generated in the dorsal neural tube, consist of about 10% of OPC in the whole spinal cord.[11] In forebrain, OPCs appear in the ventral region of ventricular zone, initially in medial ganglionic eminence (GE), and afterward in lateral GE, which are defined by the expression of the transcriptional factor Nkx2.1 and Gsh2, respectively. GE-derived OPC migrates into entire parenchyma of the brain with proliferation. OPCs are perinatally generated in the dorsal region of ventricular zone defined by the expression of Emx1 and coexist with GE-derived OPCs mainly in the neocortex. In postnatal period, OPCs are generated from the subventricular zone and distributed into the neocortex and constitutive a small population. These indicate age- and region-dependent differences in OPC cell cycle, and therefore, OPCs originally possess the heterogeneity in brain development.[12]
| Defined Factors Determines Oligodendrocyte Precursor Cells Lineage | | |
Several specific intrinsic factors have been identified to promote endothelial cells in the neural tube to organize the OPC population. In the spinal cord, sonic hedgehog (SHH) promotes the development of Olig2-expressing progenitor cells potential to differentiate into somatic motor neuron cells and OPCs.[13] Although fibroblast growth factor 2 (FGF2) has a positive regulatory effect on the proliferation of OPCs from rodent neural stem cells (NSCs), it blocks the transition of human pre-OPCs to OPCs by SHH-dependent expression of Olig2 and Nkx2.2, suggesting that intrinsic factors could exert its regulatory effect in different stage between species. Phosphorylation of Olig2 also induces to divergence in differentiation into OPCs.[14] Further specific cell fate as OPCs has been determined by intrinsic transcriptional factor, Sox10.[15]
Potent extrinsic factors have been identified which proliferate OPCs such as growth factors, neurotransmitters, signaling molecules, and extracellular matrix molecules. PDGF is one of the most potent and characterized molecules that are mainly secreted from astrocytes and neurons. PDGF-AA is a homodimer of PDGF-A subunit, has a high-affinity with PDGF-Rα highly expressed in OPCs.[4] PDGF-A-deleted mice exhibit depletion of OPCs [16] and PDGF-A transgenic mice show OPCs proliferation,[17] indicating that PDGF-Rα should be a major regulator of OPCs and the sequential maturation into OLs.
| Differentiation Into Oligodendrocyte Precursor Cells from Stem Cells | | |
According to identified intrinsic or extrinsic factors, OPCs can be differentiated from stem cells. In 1999, glial precursor cells (GPCs) have been reported to be derived from embryonic stem cells (ESCs) and contribute the myelination of the myelin-deficient rat.[18] In the study, ESCs were aggregated to embryonic bodies (EBs) and plated in a defined medium with epidermal growth factor (EGF), FGF2, and PDGF-AA. Differentiated cells were immunoreactive to A2B5 and O4 as an OL marker and also glial fibrillary acidic protein as an astrocyte marker. Recent advances using dual and Wnt/β-catenin inhibitors such as LDN, SB431542, XAV induce to robust neural lineage despite of the requirement for lengthy in vitro differentiation periods.[19],[20] ESCs were then differentiated into neural epithelial cells express PAX6, pre-OPCs express Olig2, and NKx2.2, and OPCs express PDGF-Rα and SOX10 under purmorphamine, a smoothened agonist of the hedgehog pathway.
Induced pluripotent stem cells (iPSCs) have been available for autologous engraftment of disease-relevant cells by directed differentiation using defined factors.[21] Czepiel et al. differentiated from iPSCs into functional OLs through EBs floating culture. To induce neural precursor cells, EBs were dissociated and cultured using FGF2 and EGF. They differentiated into mature OL using PDGF-AA, T3, and NT3, which were able to form myelin around the axon of cocultured dorsal root ganglion neurons in vitro and the demyelinated corpus callosum of cuprizone-fed mice without teratoma formation in vivo.[22] Wang et al. formed EBs from iPSCs and used FGF2 for neuroepithelial stage, RA, B27, purmorphamine for pre-OPCs and finally, differentiated into OPCs from iPSCs using T3, NT3, insulin-like growth factor (IGF), PDGF-AA, and purmophamine.[23] They furthermore isolated OPCs from iPSCs by fluorescence-activated cell sorting using A2B5, CD140a/PDGF-Rα, and CD9 antibodies. OPCs-transplanted homozygous shiverer rag2-null mice deficient in myelin lived almost two-time longer than control. Recipient callosa were densely myelinated and showed no evidence of tumorigenesis. OPCs readily differentiated into not only OLs but also astrocytes. For directing the maturation of OLs, they withdrew half gliogenic growth factors (PDGF-AA, IGF, and NT-3) and supplemented them with half neurobasal media plus B27 and brain-derived neurotrophic factor (BDNF). The majority of transplanted OPCs was OLs and remained OPCs (80%), and the rest of cells were astrocytes in the corpus callosum without any evidence of tumorigenesis in vivo. The myelination efficiency of implanted iPSCs-derived OPCs was as high as tissue-derived CD140a-sorted OPCs.[24]
OPC can be generated from fibroblasts by direct reprogramming [25],[26],[27] by ectopic expression of defined transcriptional factors. Induced OPC (iOPC) can expand in vitro and differentiate into mature OL ensheathing host axons and generating compact myelin.
| Efficacy Of Transplantation Of Oligodendrocyte Precursor Cells In Rodent Demyelinated Disease | | |
Several studies have been demonstrated that OPCs transplantation derived from stem cell could be effective for the rodent neuronal disease such as traumatic injury, radiation-induced demyelination, or congenital hypomyelination [Table 1]. The treatment could be fundamentally targeted based on three following principle benefits: (1) remyelination by exogenous OPCs, (2) Stabilization of the necrotic core cavity by placing proliferating OPCs into the lesion (3) enhancement of endogenous self-repairing mechanism by systematic regulation of immune response and protection by release of neurotrophins secreted from transplanted OPCs. Several studies suggested that remyelination is not always necessary for the survival of demyelinated axons [36],[37] suggesting that the combination of both benefits should be required to maximize the therapeutic potential of OPCs for clinical application. | Table 1: Oligodendrocyte precursor cell transplantation in rodent model of disease
Click here to view |
Spinal cord injury (SCI) is a white matter trauma that causes demyelination, OLs death, and remyelination. The underlying mechanisms such as ischemia, free radical production, and phagocytosis by immunoreactive cells lead to OLs cell death within hours and lasts for weeks after injury. OPCs derived from human ESCs survived, differentiated in the C5 midline contusion injury site of the cervical cord, and improve the motor function of forelimb.[30] In this study, OPCs histologically spared broad white and gray matter, induced to remyelinate and preserved motor neurons, correlated with movement recovery. Transplanted OPCs derived from human ESCs (hESCs) exhibited enhanced remyelination and promoted improvement locomotor ability only at early time points after thoracic SCI.[29] In other study, OPCs derived from hESCs transplanted into deep sensorimotor cortex migrated massively along the white matter tract and differentiated into ensheathing OLs,[28] indicating that OPCs can serve as a competent source of OLs after traumatic brain injury. NSCs derived from human fetal spinal cord, or human ESCs survived, differentiated, and filled cavity lesion in the T3 complete spinal cord transection.[38] The grafted cells primarily differentiated into neurons (27.5%), OLs (26.6%), and astrocytes (15.9%). Graft-derived axons in host white matter myelinated by host OLs and extended over long distances to connect the neural circuit and improved electrophysiological and functional outcomes. GPCs-derived OPC also contributes to myelination.[18] These studies suggest that the transplanted OPCs could functionally contribute to remyelinate motor neurons in the SCI site and give the additional protective effects other than remyelination on the remaining neurons.
X-irradiation therapy has been applied to many primary and metastatic cancers in the intracranial lesions while X-irradiation cause cognitive impairment as its side effect pathologically consisting of demyelination and necrosis in the white matter, and the main target of radiation is the large pool of mitotically active OPCs.[39],[40] Although endogenous OPCs are present in the injured white matter region after radiation, they fail to remyelinate the demyelinated axons. The establishment of exogenous OPCs requires the condition where endogenous OPCs were completely depleted, and the presence of inflammation [40],[41] implying the needs of activated immune response eliminates remaining aberrantly functional OPCs. Radiation decreased the number of OPCs accompanied with the decreased expression of myelin basic protein (MBP). When ESC-derived OPCs were grafted into the damaged cortex, they migrate throughout the white matter and remyelinate irradiated brain and ameliorates cognitive function. Moreover, when transplanted into the cerebellum, they improved the motor function.[20] It is under debate whether the improvement of cognitive and locomotive function by OPCs transplantation could be dependent on remyelination or not. Mouse-derived neural progenitor cells transplanted into irradiated mice increased the axon survival by restoring the remyelinating capacity. While there are no signs of axonal degeneration in the chronic stage of genetically mutated MBP mice.[36] Therefore, transplanted OPCs could contribute to compensate and repair the demyelinated region by some beneficial actions other than myelin sheath production.
Other adult disease such as metabolic disorders of myelin such as globoid cell leukodystrophy, Krabbe's disease, and Alexander's disease, and neurodegenerative disease associated with white matter loss and ischemic white matter disease are potential targets of OPC transplantation therapy.[31],[32],[42] Transplanted OPC promotes the BDNF and the proliferation of NSC, enhancing the endogenous self-repairing system in the ischemic brain. In regard of neural NSC transplantation, NSC overexpressing sphingomyelinase-induced the reduction in accumulated sphingomyelin in sphingomyelin-deficient Niemann–Pick type A model mice.[43] Engrafted NSC also ameliorated lipofuscin accumulation in the mouse model of neuronal ceroid lipofuscinosis,[44] raising the therapeutic possibility of the approach to the white matter-related disease by combined transplantation of the NCS and the OPCs.
| Overview Of Clinical Application Of Oligodendrocyte Precursor Cells Cell-Based Study | | |
One of the challenging aspects of the clinical approach using stem cell-derived OPCs/OLs is the requirement for lengthy culture for differentiation into late OPC/OL,[45] which prevents the injured patient from immediate cell-based therapy using stem cell-derived OPCs/OLs. The previous reports showed that it took almost 3 months to obtain functional OPCs derived from ESCs and almost 4 months from iPSCs. Further, 3 months after transplantation ES-derived OPCs matured into OLs and produced dense and compact myelin in vivo. One solution is using dual Smad and Wnt/β-catenin inhibitors which rapidly induce to neuronal lineage and shorten the differentiation period into OL.[46] OPCs derived from sources other than stem cell could be another solution for immediate OPC cell therapy following demyelinated neuronal disease. Bone marrow stromal cell-derived OPC mitigated demyelination and augmented remyelination in lysophosphatidylcholine-injected demyelinated rodent brain.[25] Extracted OPCs from fetal or adult brain are also available, which infiltrated into the forebrain when xenografted to congenitally or chemically demyelinated mouse.[33],[34] However, this method is challenging for clinical application since the postmitotic state impedes the large-scale expansion. Ectopic expression of transcriptional factor Oct4 in fibroblast generates self-renewing and bipotent OPC (iOPC), which is a powerful and promising source for OPC cell-based therapy. This iOPC is available about 1 month after reprograming and can proliferate through over thirty times of self-renewals. This method bypasses undifferentiated stem cell state and limits the tumorigenic potential after transplantation.[47] Transplanted iOPCs enhanced recovery of locomotion in a rodent SCI model.[27]
Taken together, cell-based OPC therapy may give the following beneficial cellular effects in the injured region: Remyelination, heterogeneous OL/astrocytes cell replacement in the cavity, and the enhancement of functional NSC through secreted neurotrophins. Further investigation of the mechanism of OPC lineage and development of stem cell technology will translate the OPC research into clinical benefits for the patients of demyelinating disorders in near future.
Financial support and sponsorship
National Institute of Health.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Raff MC, Miller RH, Noble M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 1983;303:390-6.  |
| 2. | Nishiyama A, Chang A, Trapp BD. NG2+glial cells: A novel glial cell population in the adult brain. J Neuropathol Exp Neurol 1999;58:1113-24. |
| 3. | Nishiyama A, Komitova M, Suzuki R, Zhu X. Polydendrocytes (NG2 cells): Multifunctional cells with lineage plasticity. Nat Rev Neurosci 2009;10:9-22. |
| 4. | Hart IK, Richardson WD, Heldin CH, Westermark B, Raff MC. PDGF receptors on cells of the oligodendrocyte-type-2 astrocyte (O-2A) cell lineage. Development 1989;105:595-603. |
| 5. | Dawson MR, Polito A, Levine JM, Reynolds R. NG2-expressing glial progenitor cells: An abundant and widespread population of cycling cells in the adult rat CNS. Mol Cell Neurosci 2003;24:476-88. |
| 6. | Peters A. A fourth type of neuroglial cell in the adult central nervous system. J Neurocytol 2004;33:345-57. |
| 7. | Kondo T, Raff M. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science 2000;289:1754-7. |
| 8. | Lu QR, Yuk D, Alberta JA, Zhu Z, Pawlitzky I, Chan J, et al. Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bhlh proteins in the mammalian central nervous system. Neuron 2000;25:317-29. |
| 9. | Takebayashi H, Yoshida S, Sugimori M, Kosako H, Kominami R, Nakafuku M, et al. Dynamic expression of basic helix-loop-helix Olig family members: Implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3. Mech Dev 2000;99:143-8. |
| 10. | Zhou Q, Wang S, Anderson DJ. Identification of a novel family of oligodendrocyte lineage-specific basic helix-loop-helix transcription factors. Neuron 2000;25:331-43. |
| 11. | Hill RA, Patel KD, Goncalves CM, Grutzendler J, Nishiyama A. Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division. Nat Neurosci 2014;17:1518-27. |
| 12. | Hill RA, Nishiyama A. NG2 cells (polydendrocytes): Listeners to the neural network with diverse properties. Glia 2014;62:1195-210. |
| 13. | Hu BY, Du ZW, Li XJ, Ayala M, Zhang SC. Human oligodendrocytes from embryonic stem cells: Conserved SHH signaling networks and divergent FGF effects. Development 2009;136:1443-52. |
| 14. | Li H, de Faria JP, Andrew P, Nitarska J, Richardson WD. Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch. Neuron 2011;69:918-29. |
| 15. | Hornig J, Fröb F, Vogl MR, Hermans-Borgmeyer I, Tamm ER, Wegner M. The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes. PLoS Genet 2013;9:e1003907. |
| 16. | Fruttiger M, Karlsson L, Hall AC, Abramsson A, Calver AR, Boström H, et al. Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 1999;126:457-67. |
| 17. | Woodruff RH, Fruttiger M, Richardson WD, Franklin RJ. Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult cns and their response following cns demyelination. Mol Cell Neurosci 2004;25:252-62. |
| 18. | Brüstle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, et al. Embryonic stem cell-derived glial precursors: A source of myelinating transplants. Science 1999;285:754-6. |
| 19. | Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 2009;27:275-80. |
| 20. | Piao J, Major T, Auyeung G, Policarpio E, Menon J, Droms L, et al. Human embryonic stem cell-derived oligodendrocyte progenitors remyelinate the brain and rescue behavioral deficits following radiation. Cell Stem Cell 2015;16:198-210. |
| 21. | Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-72. |
| 22. | Czepiel M, Balasubramaniyan V, Schaafsma W, Stancic M, Mikkers H, Huisman C, et al. Differentiation of induced pluripotent stem cells into functional oligodendrocytes. Glia 2011;59:882-92. |
| 23. | Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, et al. Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 2013;12:252-64. |
| 24. | Sim FJ, McClain CR, Schanz SJ, Protack TL, Windrem MS, Goldman SA. CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nat Biotechnol 2011;29:934-41. |
| 25. | Nazm Bojnordi M, Ghasemi HH, Akbari E. Remyelination after lysophosphatidyl choline-induced demyelination is stimulated by bone marrow stromal cell-derived oligoprogenitor cell transplantation. Cells Tissues Organs 2014;200:300-6. |
| 26. | Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, et al. Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol 2013;31:434-9. |
| 27. | Kim JB, Lee H, Araúzo-Bravo MJ, Hwang K, Nam D, Park MR, et al. Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model. EMBO J 2015;34:2971-83. |
| 28. | Xu L, Ryu J, Hiel H, Menon A, Aggarwal A, Rha E, et al. Transplantation of human oligodendrocyte progenitor cells in an animal model of diffuse traumatic axonal injury: Survival and differentiation. Stem Cell Res Ther 2015;6:93. |
| 29. | Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, et al. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 2005;25:4694-705. |
| 30. | Sharp J, Frame J, Siegenthaler M, Nistor G, Keirstead HS. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells 2010;28:152-63. |
| 31. | Chen LX, Ma SM, Zhang P, Fan ZC, Xiong M, Cheng GQ, et al. Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury. PLoS One 2015;10:e0115997. |
| 32. | Kuai XL, Ni RZ, Zhou GX, Mao ZB, Zhang JF, Yi N, et al. Transplantation of mouse embryonic stem cell-derived oligodendrocytes in the murine model of globoid cell leukodystrophy. Stem Cell Res Ther 2015;6:30. |
| 33. | Windrem MS, Nunes MC, Rashbaum WK, Schwartz TH, Goodman RA, McKhann G 2 nd, et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 2004;10:93-7. |
| 34. | Windrem MS, Roy NS, Wang J, Nunes M, Benraiss A, Goodman R, et al. Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain. J Neurosci Res 2002;69:966-75. |
| 35. | Webber DJ, van Blitterswijk M, Chandran S. Neuroprotective effect of oligodendrocyte precursor cell transplantation in a long-term model of periventricular leukomalacia. Am J Pathol 2009;175:2332-42. |
| 36. | Smith CM, Cooksey E, Duncan ID. Myelin loss does not lead to axonal degeneration in a long-lived model of chronic demyelination. J Neurosci 2013;33:2718-27. |
| 37. | Loers G, Aboul-Enein F, Bartsch U, Lassmann H, Schachner M. Comparison of myelin, axon, lipid, and immunopathology in the central nervous system of differentially myelin-compromised mutant mice: A morphological and biochemical study. Mol Cell Neurosci 2004;27:175-89. |
| 38. | Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, et al. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell 2012;150:1264-73. |
| 39. | Panagiotakos G, Alshamy G, Chan B, Abrams R, Greenberg E, Saxena A, et al. Long-term impact of radiation on the stem cell and oligodendrocyte precursors in the brain. PLoS One 2007;2:e588. |
| 40. | Chari DM, Gilson JM, Franklin RJ, Blakemore WF. Oligodendrocyte progenitor cell (opc) transplantation is unlikely to offer a means of preventing X-irradiation induced damage in the cns. Exp Neurol 2006;198:145-53. |
| 41. | Blakemore WF, Irvine KA. Endogenous or exogenous oligodendrocytes for remyelination. J Neurol Sci 2008;265:43-46. |
| 42. | Goldman SA, Nedergaard M, Windrem MS. Glial progenitor cell-based treatment and modeling of neurological disease. Science 2012;338:491-5. |
| 43. | Shihabuddin LS, Numan S, Huff MR, Dodge JC, Clarke J, Macauley SL, et al. Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology. J Neurosci 2004;24:10642-51. |
| 44. | Tamaki SJ, Jacobs Y, Dohse M, Capela A, Cooper JD, Reitsma M, et al. Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis. Cell Stem Cell 2009;5:310-9. |
| 45. | Tabar V, Studer L. Pluripotent stem cells in regenerative medicine: Challenges and recent progress. Nat Rev Genet 2014;15:82-92. |
| 46. | Chambers SM, Qi Y, Mica Y, Lee G, Zhang XJ, Niu L, et al. Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat Biotechnol 2012;30:715-20. |
| 47. | Fong CY, Gauthaman K, Bongso A. Teratomas from pluripotent stem cells: A clinical hurdle. J Cell Biochem 2010;111:769-81. |
[Table 1]
| This article has been cited by | | 1 |
Development of Brain-Derived Bioscaffolds for Neural Progenitor Cell Culture |
|
| Julia C. Terek, Matthew O. Hebb, Lauren E. Flynn | | ACS Pharmacology & Translational Science. 2023; | | [Pubmed] | [DOI] | | | 2 |
Coactivator-associated arginine methyltransferase 1 controls oligodendrocyte differentiation in the corpus callosum during early brain development |
|
| Yugo Ishino, Shoko Shimizu, Masaya Tohyama, Shingo Miyata | | Developmental Neurobiology. 2022; | | [Pubmed] | [DOI] | | | 3 |
Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease |
|
| Christophe Galichet,Richard W. Clayton,Robin Lovell-Badge | | Frontiers in Cellular Neuroscience. 2021; 15 | | [Pubmed] | [DOI] | | | 4 |
Intranasal Administration of Undifferentiated Oligodendrocyte Lineage Cells as a Potential Approach to Deliver Oligodendrocyte Precursor Cells into Brain |
|
| Ulises Gómez-Pinedo,Jordi A. Matías-Guiu,María Soledad Benito-Martín,Lidia Moreno-Jiménez,Inmaculada Sanclemente-Alamán,Belen Selma-Calvo,Sara Pérez-Suarez,Francisco Sancho-Bielsa,Alejandro Canales-Aguirre,Juan Carlos Mateos-Díaz,Mercedes A. Hernández-Sapiéns,Edwin E. Reza-Zaldívar,Doddy Denise Ojeda-Hernández,Lucía Vidorreta-Ballesteros,Paloma Montero-Escribano,Jorge Matías-Guiu | | International Journal of Molecular Sciences. 2021; 22(19): 10738 | | [Pubmed] | [DOI] | | | 5 |
Human Pluripotent Stem Cells for Spinal Cord Injury |
|
| Maryam Farzaneh,Amir Anbiyaiee,Seyed Esmaeil Khoshnam | | Current Stem Cell Research & Therapy. 2020; 15(2): 135 | | [Pubmed] | [DOI] | | | 6 |
Stem cells and tooth regeneration: prospects for personalized dentistry |
|
| Mahmood S. Mozaffari,Golnaz Emami,Hesam Khodadadi,Babak Baban | | EPMA Journal. 2019; | | [Pubmed] | [DOI] | |
|
 |
|
|
|
Search Pubmed for