From: Glial-restricted progenitor cells: a cure for diseased brain?
Type of transplanted cells | Source of transplanted cells | Animal model / recipient | Number of transplanted cells | Delivery route | Observation time | Molecular outcome | Functional outcome | Human disease model | References |
---|---|---|---|---|---|---|---|---|---|
GRPs | I. Human fetal brain II. Human adult brain | Shiverer mice | 1 × 105 | Intracerebral | 3 months | Oligodendrocytes Astrocytes Compact myelin | Not determined | Hypomyelinating disease | [173] ** |
GRPs | Human fetal brain | Shiverer mice | 3 × 105 | Intracerebral |  > 1 year | Oligodendrocytes Compact myelin | Increased survival Reduced seizure frequency | Hypomyelinating disease | [174] * |
GRPs | Human fetal brain | Shiverer mice | 0.5 × 105 | Intracerebral | 12 weeks | Oligodendrocytes Astrocytes Compact myelin | Not determined | Hypomyelinating disease | [142] * |
GRPs | Human fetal brain | Shiverer mice | 3 × 105 | Intracerebral | 1 year | Humanization of mice brain Oligodendrocytes Astrocytes | Improved cognition Increased survival | Hypomyelinating disease | [175] ** |
GRPs | I. Mouse fetal brain II. Human fetal brain | Shiverer mice | 2 × 105 | Intraventricular | I. 46 weeks II. 62 weeks | I. Early compact myelin formation with limited cell migration II. Late compact myelin formation with extensive cell migration | None | Hypomyelinating disease | [88] ** |
GRPs | Human fetal brain | I. Shiverer mice II. Mice with cuprizone demyelination | 2 × 105 | Intracerebral | 20 weeks | Oligodendrocytes Compact myelin Improved nerve conduction | Improved motor behaviour | Hypomyelinating disease | [176] |
GRPs | Canine fetal brain and spinal cord | Shiverer mice | 2 × 105 | Intraventricular | Up to 400 days | Partial remyelination | Extended survival | Hypomyelinating disease | [147] |
OPCs | hESCs | Brain irradiated nude rats | 1 × 106 | Intracerebral | 10 weeks | Oligodendrocytes Compact myelin | Recovery from motor deficits | Hypomyelinating disease | [124] |
OPCs | hiPSCs from MS patients | Shiverer mice | 1 × 105 | Intracerebral | 12–16 weeks | Myelinating oligodendrocytes | Not determined | Hypomyelinating disease | [26] |
OPCs | hESCs | Shiverer mice | 4 × 105 | Intraspinal | 6 weeks | Oligodendrocytes Compact myelin | Not determined | Hypomyelinating disease | [113] * |
OPCs | hiPSCs | Shiverer mice | I. 1 × 105 II. 3 × 105 | Intracerebral | 9 months | Oligodendrocytes Astrocytes Compact myelin | Increased survival | Hypomyelinating disease | [169] |
OPCs overexpressing Zfp488 | hiPSCs | Shiverer mice | 5 × 105 | Intracerebral | 8 weeks | Oligodendrocytes Compact myelin | Not determined | Hypomyelinating disease | [13] |
OPCs | mESCs | Twitcher mice | 0.2 × 105 | Intracerebral |  ~ 3 weeks | Modest myelination | None | Leukodystrophy | [71] |
OPCs | Rat fetal brain | ARSA null neonate mice | 1.5 × 105 | Intraventricular | 60 days | Increased brain ARSA activity | Prevention of motor deficits | Leukodystrophy | [36] |
GRPs/OPCs (sorted for: A2B5+, GLAST+, and PDGFαR+ populations) | Mouse fetal brain | Mice with vanishing white matter | 6 × 105 | Intracerebral | 9 months | Astrocytes Oligodendrocytes | Selectively improved motor skills | Leukodystrophy | [25] |
GRPs | Rat fetal brain | SOD1 G93A rats | 9 × 105 | Intraspinal | 80 days | Astrocytes Oligodendrocytes Reduced microgliosis | Increased survival Improved motor performance | ALS | [78] * |
GRPs | Human fetal brain | SOD1 G93A mice | I. 2 × 105 II. 6 × 105 | Intraspinal | 130 days | Astrocytes Oligodendrocytes | None | ALS | [77] |
GRPs | Human fetal brain | SOD1 G93A mice | 3 × 105 | Intraspinal | 90 days | Retained characteristics of GRPs | Not determined | ALS | [46] |
GRPs | Human fetal brain | SOD1 G93A mice | 4 × 105 | Intracerebral | Up to 300 days | None | None | ALS | [148] |
GRPs | hiPSCs | SOD1 G93A mice | 8 × 104 | Intraspinal | up to 90 days | Astrocytes | Increased survival Improved clinical motor score | ALS | [67] * |
GRPs | Mouse fetal brain | MHV-infected mice | 2.4 × 105 | Intraspinal | 33 days | Remyelination Axonal sparing | Locomotor recovery | MS | [158] |
GRPs | Mouse fetal brain | MHV-infected mice | 2.4 × 105 | Intraspinal | 21 days | Remyelination without attenuated inflammatory response | Not determined | MS | [49] |
OPCs | hESCs | EAE mice | 1 × 106 | Intraventricular | 15 days | Immunomodulation | Improved neurological disability score | MS | [64] |
OPCs | hWJ-MSCs | EAE mice | 1 × 106 | Intracerebroventricular | 50 days | Increased remyelination | Reduced symptoms | MS | [97] |
OPCs | hESCs | MS mice | 1 × 106 | Intracerebroventricular | 65 days | Reduced inflammation Reduced demyelination Reduced axonal loss | Long term disease attenuation | MS | [112] |
GRPs | Mouse fetal brain | Wild-type mice (later subjected to brain trauma) | 4 × 105 | Intracerebroventricular | 16 weeks | Enhanced GRP engraftment and tissue repair after brain trauma | Not determined | Brain injury | [168] |
OPCs | Human fetal brain | Ischemic stroke rats | 3 × 105 | I. Intraventricular Ii. Intracerebral |  ~ 90 days | Thick myelin sheath Reduced brain structural damage | Enhanced modified neurological severity score | Brain injury | [177] |
OPCs | Human fetal brain | H/I brain injury + LPS injected rats | 4 × 105 | Intracerebroventricular | 45 days | Myelinating oligodendrocytes | Improved locomotor and cognitive performance | Brain injury | [66] |
OPCs | Human fetal brain | Ischemic stroke gerbils | 1 × 106 | Intravenous | 30 days | Restored myelination | Improved memory and cognition | Brain injury | [1] |
OPCs | mESCs | Ischemic stroke rats | 2 × 105 | Intraventricular | 6 weeks | Myelin Apoptosis inhibition | Improved spatial learning and memory | Brain injury | [18] |
OPCs | hESCs | Global cerebral ischemic rats | 5 × 105 | Intracerebroventricular | 2 weeks | Astroglia Preserved myelin integrity | Improved learning and memory | Brain injury | [57] |
OPCs | Mouse adult brain | MCAO mice | 6 × 105 | Intracerebral | Up to 14 days | Alleviated edema and infarct volume Reduced blood–brain barrier leakage | Neurological recovery promotion | Brain injury | [167] |
OPCs | hESCs | Marmarou weight drop injury rat model | 2 × 105 | Intracerebral | 3 months | Ensheathing oligodendrocytes | Not determined | Brain injury | [179] |
CM from GRPs | hiPSCs | MCAO rats | 50 µg of total protein | Intraarterial | 30 days | Enhanced angiogenesis Cytoprotection Anti-inflammatory effect | Neurological improvement | Brain injury | [137] |
GRPs loaded with PAMAM | Mouse fetal spinal cord | Ischemic stroke mice | 1 × 105 | Intracerebral | 8 weeks | Improved GRPs migration and differentiation | Not determined | Brain injury | [108] |
GRPs overexpressing VLA-4 | Mouse fetal brain | MCAO mice | 1 × 106 | Intraarterial | 30 days | Increased efficiency of GRPs' docking Diapedesis induction | Not determined | Brain injury | [55] * |
GRPs | Rat fetal spinal cord | SCI rats | 3 × 105 | Intraspinal | 3 weeks | Astrocytes Promotion of axonal growth | Not determined | SCI | [45] |
GRPs | Human fetal brain | SCI rats | 6 × 105 | Intraspinal | 5 weeks | Astrocytes Axonal regeneration | Not determined | SCI | [44] * |
GRPs | Human fetal brain | SCI rats | 1 × 106 | Intraspinal | 8 weeks | Mostly astrocytes Reduced glial scar | Attenuated hyperactive bladder reflexes | SCI | [58] |
GRPs | Human fetal brain | SCI rats | 4 × 105 | Intraspinal | 95 days | Preserved electrophysiological conduction Myelination Astrocytes Modest generation of oligodendrocytes | None | SCI | [165] ** |
GRPs | Rat fetal spinal cord | SCI rats | 2 × 105 | Intraspinal | 5 weeks | Astrocytes Oligodendrocytes | Not determined | SCI | [48] |
GRPs | Rat fetal brain | SCI rats | 2–3 × 106 | Intraspinal | 12 weeks | Integration within the host tissue Astrocytic and oligodendrocytic differentiation | Recovery of erectile events and locomotion functions | SCI | [114] |
OPCs | hiPSCs | SCI rats | 5 × 105 | Intraspinal | 2 months | Mature oligodendrocytes Reduced cavity size Increased number of myelinated axons | Partial motor recovery | SCI | [3] |
OPCs | miPSCs | SCI rats | 5 × 106 | Intraspinal | 4 weeks | Promoted myelin formation | Attenuated motor and sensory dysfunction | SCI | [188] |
OPCs | hESCs | SCI rats | I. 15 × 105 II. 2.5 × 105 | Intraspinal | 8 weeks | Oligodendrocytes Improved myelination | Improved motor function | SCI | [62] * |
OPCs | hiPSCs | SCI rats | 5 × 105 | Intraspinal | 12 weeks | Oligodendrocytes Neurons | None | SCI | [122] |
OPCs | hESCs | SCI rats | 2.4 × 105—2.4 × 106 | Intraspinal | 12 months | Neurite outgrowth Myelination | No adverse clinical observations (allodynia, toxicity, or tumor formation) | SCI | [127] |
OPCs | hiPSCs | SCI rats | I. Efficacy dose: 2.4 × 105 II. Maximum feasible dose: 2.4 × 106 | Intraspinal | 4 months | Reduction in parenchymal cavitation at the injury site Increased number of myelinated axons | Improved locomotor performance | SCI | [90] |
OPCs | hESCs | SCI rats | 1 × 106 | Intraspinal | 8 weeks | Neural rescue | Movement recovery | SCI | [140] |
OPCs | Human fetal brain | SCI rats | I. Hemisection: 1.5 × 106 II. Dorsal column: 1 × 106 | Intraspinal | 5 weeks | Promotion of sensory and motor axonal regeneration | Not determined | SCI | [59] |
OPCs | hESCs | SCI patients (clinical trial NCT02302157) | I. 2 × 106 II. 1 × 107 III. 2 × 107 | Intraparenchymal | 1 year | No: enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the VS | Moderate recovery of neurological functions | SCI (clinical trial) | [30] ** |
GRPs overexpressing GLT1 | Rat fetal spinal cord | SCI rats | I. 6 × 105 II. 9 × 105 | Intraspinal | 5 weeks | Reduced lesion size, diaphragm denervation and diaphragm dysfunction | Not determined | SCI | [80] |
OPCs overexpressing microRNA-219 | hiPSCs | SCI rats | 1 × 106 | Intraspinal | 2 months | Mature oligodendrocytes | Improved locomotor activity | SCI | [107] |
OPCs overexpressing MRF + Schwann cells | Rat fetal spinal cord | SCI rats | 2 × 105 of each cell type | Intraspinal | 6 weeks | Increased myelination and tissue repair | Recovery of neurological function | SCI | [178] |
OPCs overexpressing PDGF-AA | Rat fetal spinal cord | SCI rats | 2 × 105 | Intraspinal | 7 weeks | Increased myelination and tissue repair | Recovery of neurological function | SCI | [186] |