Table 1.

Selected studies carried out with PSC-derived cells for acute and chronic SCI.

SCI Phase	Type of SCI	Animal Model	Level of Injury	Injected Cells	Number of Cells	Application Route	Timing of Transplantation	Tests Used for the Assessment of Recovery	Outcome	Year	Reference
Acute	Contusion	Rat	Thoracic	Mouse RA-differentiated ESC–NSC	1 × 106	At the lesion epicenter	9 days PI	BBB	Locomotor recovery	1999	[15]
	Contusion	Rat	Thoracic	Human ESC–OPC	2.5 × 105 or 1.5 × 106	Rostral and caudal to the lesion epicenter	7 days PI	BBB and 4 parameter kinematic analyses	Locomotor recovery	2005	[23]
	Contusion	Mouse	Thoracic	Mouse ESC–NSC	2 × 104	At the lesion epicenter	10 days PI	Motor score, platform hang and rope walk	Locomotor recovery	2005	[16]
	Contusion	Rat	Thoracic	Human ESC–OPC	1.5 × 106	Rostral and caudal to the lesion epicenter	7 days PI	BBB	Transplantation per se did not decrease locomotor function	2006	[24] #
	Contusion	Mouse	Thoracic	Mouse ESC–primary and secondary neurospheres	5 × 105	At the lesion epicenter	9 days PI	BMS	Locomotor recovery	2009	[17] *
	Compression	Rat	Thoracic	Mouse ESC-motorneurons + OEC	1 × 106	At the lesion epicenter	9 days PI	BBB	Locomotor recovery	2009	[36]
	Contusion	Rat	Cervical	Human ESC–OPC	1.5 × 106	Rostral and caudal to the lesion epicenter	7 days PI	Forelimb movement scores	Locomotor recovery	2010	[30]
	Compression	Mouse	Thoracic	Mouse ESC–neural aggregates overexpressing L1	2 × 105	Rostral and caudal to the lesion epicenter	3 days PI	BBB score, foot-stepping angle and rump-height index	Locomotor recovery	2011	[20]
	Contusion	Rat	Thoracic	Human ESC–NSC + Schwann cells	5 × 105 (NSC or Schwann cells) or 1 × 106 (NSC + Schwann cells)	At the lesion epicenter	7 days PI	BBB	Locomotor recovery	2012	[35]
	Transection	Rat	Thoracic	Human ESC–NSC in fibrin with a growth factor cocktail	2 × 106	At the lesion epicenter	7 days PI	BBB, 21-point locomotion rating scale, electrophysiological assessment	Locomotor recovery	2012	[18]
	Contusion	Rat; mouse	Thoracic	Human ESC–OPC	Rats: 2.4 × 105 or 2.4 × 106. Mice: 2.5 × 105 to 1 × 106	Rats: 4 injections at the perimeter of the lesion or 1 injection rostral to the lesion epicenter. Mice: rostral to the lesion epicenter.	6–8 days PI	None	Locomotor recovery in previous studies (see [23,24])	2015	[25]
	Contusion	Rat	Thoracic	NG2 and MMP9 positive mouse ESC–NSC	1 × 106	At the lesion epicenter	9 days PI	None	Axonal outgrowth into white matter	2015	[32]
	Contusion	Marmoset	Cervical	OPC-enriched marmoset ESC–NSC	1 × 106	At the lesion epicenter	14 days PI	Open field and bar grip strength test	Locomotor recovery	2015	[31] *
	Contusion	Mouse	Thoracic	Human ESC-derived inhibitory interneuron precursors	3 × 105 or 6–8 × 105	Caudal to the injury epicenter	15 days PI	BMS, Allodynia, Thermal hyperalgesia and bladder functional tests	Absence of locomotor recovery	2016	[34]
	Contusion	Mouse	Thoracic	Mouse ESC–NSC overexpressing BDNF	1 × 105	At the lesion epicenter	7 days PI	BMS	Locomotor recovery	2016	[19]
	Contusion	Rat	Thoracic	Mouse ESC–NSC	1 × 106	At the lesion epicenter	21 days PI	BBB and CBS	Absence of locomotor recovery	2016	[33]
	Contusion	Mouse	Thoracic	Murine iPSC and ESC–primary and secondary neurospheres	5 × 105	At the lesion epicenter	9 days PI	BMS	Locomotor recovery	2010	[40] *
	Contusion	Rat	Thoracic	Mouse iPSC–derived astrocytes	1 × 105	At the lesion epicenter	3–7 days PI	BBB, inclined-plane test, SCANET MV-40, sensory tests	Absence of locomotor recovery	2011	[41]
	Contusion	Marmoset	Cervical	Human iPSC–secondary and tertiary neurospheres	1 × 106	At the lesion epicenter	9 days PI	Open field, bar grip, and cage climbing tests.	Locomotor recovery	2012	[42] *
	Contusion	Mouse	Thoracic	Human iPSC–NSC	1 × 106	At the lesion epicenter	7 days PI	BMS, MEPs	Locomotor recovery	2012	[43]
	Hemisection	Rat	Cervical	Human iPSC–NSC in a fibrin matrix and growth factor cocktail	1.25 × 106	Three pairs of injections 0.5 mm apart, at the center, rostral, and caudal to the center of the lesion cavity	14 days PI	Grid-walking, forelimb grooming and LUAT	Absence of locomotor recovery	2014	[44]
	Compression	Rat	Thoracic	Human iPSC–NSC	5 × 105	At the lesion epicenter	7 days PI	BBB, plantar test, beam walking test, and RotaRod	Locomotor recovery	2015	[45]
	Compression	Mouse	Thoracic	Mouse iPSC–NSC	2 × 105	Four injections flanking the injury	7 days PI	BMS, CatWalk, mechanical and thermal allodynia tests.	Locomotor recovery	2015	[46]
	Contusion	Mouse	Thoracic	Murine iPSC-derived neurospheres	5 × 105	At the lesion epicenter	9 days PI	BMS, RotaRod and DigiGait	Locomotor recovery	2011, 2015	[47,48] *
	Contusion	Mouse	Thoracic	Human iPSC–NSC	4 × 105	Rostral and caudal to the lesion epicenter	7 days PI	BMS and Catwalk	Absence of locomotor recovery	2015	[49]
	Compression	Rat	Thoracic	Human iPSC–NSC	5 × 105	At the lesion epicenter	7 days PI	BBB, plantar test, beam walking test and RotaRod	Locomotor recovery	2015	[50]
	Compression	Rat	Thoracic	Human iPSC-OPC in a hydrogel with RGD and PDGF-A	8 × 105	Rostral and caudal to the lesion epicenter	7 days PI	BBB	Locomotor recovery	2016	[51]
	Contusion	Mouse	Thoracic	Human iPSC–OPC	5 × 105	At the lesion epicenter	9 days PI	BMS, RotaRod and DigiGait	Locomotor recovery	2016	[52] *
	Contusion	Mouse	Thoracic	Human iPSC–NSC treated with γ-secretase inhibitor	5 × 105	At the lesion epicenter	9 days PI	BMS	Locomotor recovery	2016	[53] *
	Contusion	Mouse	Thoracic	Human iPSC–NSC	5 × 105	At the lesion epicenter	9 days PI	BMS	Locomotor recovery (declined when tumors formed)	2017	[54] *
	Compression	Rat	Thoracic	Human iPSC–NSC conditioned with EI-tPA	1.5 × 106	At the lesion epicenter	7 days PI	BBB	Locomotor recovery	2019	[55]
	Contusion	Mouse	Thoracic	Human iPSC–spinal cord–NSC	5 × 105	At the lesion epicenter	9 days PI	BMS, RotaRod and treadmill analysis	Locomotor recovery	2020	[56] *
	Contusion	Mouse	Thoracic	Human iPSC–NSC	1 × 105	Rostral to the lesion epicenter	7 days PI	BMS	Locomotor recovery	2021	[57]
	Contusion	Rat	Thoracic	Human iPSC–NSC + MSC + PA-C	1.8 × 106	Rostral, caudal, and at the lesion epicenter	7 days PI	BBB and Catwalk	Absence of locomotor recovery	2021	[58]
Chronic	Contusion	Rat	Thoracic	Human ESC–OPC	2.5 × 105 or 1.5 × 106	Rostral and caudal to the lesion epicenter	10 months PI	BBB and four-kinematic analyses	Absence of locomotor recovery	2005	[23]
	Contusion	Rat	Cervical	Human iPSC–NSC	2 × 105	Rostral and caudal to the lesion epicenter	30 days PI	LUAT, FRT, allodynia test	Absence of locomotor recovery	2013	[59]
	Contusion	Mouse	Thoracic	Human iPSC–NSC treated with γ-secretase inhibitor	5 × 105	At the lesion epicenter	42 days PI	BMS, RotaRod and treadmill analysis	Locomotor recovery	2018	[60] *
	Compression	Rat	Thoracic	Human iPSC–NSC on Laminin-Coated pHEMA-MOETACl Hydrogel	3 × 105	At the lesion epicenter	35 days PI	BBB, plantar test	Absence of locomotor recovery	2019	[61]
	Accidental SCI	Dog	Thoracic	Canine iPSC–NSC	2 × 106	At the lesion epicenter, and one vertebral space caudal and rostral to the lesion	>28 days PI	Neurological and electrophysiological evaluation	Absence of locomotor recovery	2020	[62]
	Contusion	Rat	Thoracic	Glial scar photo-ablation + iPSC–regionally specific spinal pre-OPC	5 × 105	Rostral and caudal to the lesion epicenter	70 days post-injury	BBB	Absence of locomotor recovery	2021	[63]
	Contusion	Rat	Cervical	Human iPSC–NSC	4 × 105	Rostral and caudal to the lesion epicenter	28 days PI	FRT, IBB, and LUAT	Absence of locomotor recovery	2021	[64]

SCI: spinal cord injury; PI: post-injury; RA: retinoic acid; ESC: embryonic stem cells; NSC: neural stem cells; OPC: oligodentrocyte progenitor cells; OEC: olfactory ensheathing cells; NG2: nerve glial antigen 2; MMP9: matrix metalloprotease 9; BDNF: brain-derived neurotrophic factor; RGD: arginine–glycine–aspartate peptide: PDGF-A: platelet-derived growth factor A; EI-tPA: enzymatically inactive tissue-type plasminogen activator; MSC: mesenchymal stem cells; PA-C: pH-responsive polyacetal–curcumin nanoconjugate; pHEMA: poly(2-hydroxyethyl methacrylate); MOETACl: co-monomer (2-(methacryloyloxy) ethyl trimethylammonium chloride; BBB: Basso, Beattie, and Bresnahan test; BMS: Basso mouse scale; CBS: combined behavioral score; MEPs: motor-evoked potentials; LUAT: limb-use asymmetry test; FRT: forelimb reaching task; IBB: Irvine, Beatties and Bresnahan test; GABA: Gamma aminobutyric acid. ^# Keirstead Laboratory; * Okano Laboratory.