Glial-restricted progenitor cells: a cure for diseased brain?

Rogujski, Piotr; Lukomska, Barbara; Janowski, Miroslaw; Stanaszek, Luiza

doi:10.1186/s40659-024-00486-1

Biological Research

Table 1 Experimental studies using GRPs and OPCs in cellular therapies for glia regeneration in different models of neurological diseases

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]

ALS amyotrophic lateral sclerosis, ARSA arylsulfatase A, CM conditioned medium, EAE experimental autoimmune encephalomyelitis, GRPs glial-restricted progenitors, H/I hypoxia/ischemia, hESC human embryonic stem cell, hiPSC human induced pluripotent stem cell, hWJ-MSC human Wharton jelly-derived mesenchymal stem cell, LPS lipopolysaccharide, MCAO middle cerebral artery occlusion, mESC mouse embryonic stem cell, MHV mouse hepatitis virus, miPSC mouse induced pluripotent stem cell, MRF myelin regulatory factor, MS multiple sclerosis, OPCs oligodendrocyte progenitor cells, PAMAM hydroxyl polyamidoamine dendrimer, PDGF-AA platelet-derived growth factor-AA, SCI spinal cord injury, SOD1 superoxide dismutase-1, VLA4 very late antigen 4, VS ventricular system
*Denotes an article of special interest
**Denotes an article of outstanding interest

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ISSN: 0717-6287

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