Current status and future perspectives on stem cell transplantation for spinal cord injury

Table 6 Summary of the studies included in the systematic literature review focusing on nervous tissue derived stem cells (i.e., UCMSC, HUCBC, HESC, WJ-MSC)

Ref.	Phase of clinical trial	Patients (n)	Localization of injury	Pre-treatment AIS classification or level of injury	Stem cells		Treatment			Follow up (months)	Outcomes
					Origin	Type	Dose	Administration route	Time from injury		Functional improvement	Adverse effects
Dai et al[29], 2013	N/A	18	Cervical and thoracic	AIS A: 12, AIS B: 4, AIS C: 2	Allogeneic neonatal umbilical cord tissue	UCMSC	4 × 107	Intralesional	Chronic (18.67 ± 7.6 months)	6	AIS A→B: 7, AIS B→C: 3, AIS=: 8; MEP improvements	No serious adverse effects
Liu et al[73], 2013	N/A	22	Cervical (4), cervical + thoracic (2), thoracic + lumbar (2) and lumbar (7)	Motor function: 58.1 ± 22.2. Algesia: 73.2 ± 25.1. Sensory function: 74.2 ± 26.7. ADL: 29.5 ± 12.5	Allogeneic neonatal umbilical cord tissue	UCMSC	4 × 106/kg	Intrathecal	Intermediate and chronic (2-204 months)	> 12	Motor function: 61.5 ± 23.9. Algesia: 77.2 ± 26.1. Sensory function: 77.3 ± 26.1. ADL: 32.7 ± 12.4	Fever, lumbago, headache, dizziness and other adverse reactions were observed
Cheng et al[74], 2014	N/A	10	Thoracic and lumbar	AIS A, Barthel Index: 33.50 ± 6.69	Allogeneic neonatal umbilical cord tissue	UCMSC	4 × 107	Intralesional	Chronic (12-72 months)	6	Barthel Index: 41.40 ± 6.42; Muscle strength increased. Muscle tension decreased. Increase in maximum bladder capacity and decrease in maximum detrusor pressure	No serious adverse effects
Shroff et al[34], 2016	N/A	226	Cervical and thoracic	AIS A: 153, AIS B: 32, AIS C: 36, AIS D: 5	Pre-implantation stage fertilized ovum	HESC	1.6 × 107 + 1-5 × 1.6 × 107	Intravenous + intralesional	Intermediate and chronic	6-18	AIS A: 98, AIS B: 67, AIS C: 126, AIS D: 9, AIS E: 3	No serious adverse effects. Transient fever and headache
Shroff et al[75], 2017	N/A	15	Cervical and thoracic	AIS A: 13, AIS B: 2	Pre-implantation stage fertilized ovum taken during natural IVF process	HESC	1.6 × 107 + 1-5 × 1,6 × 107	Intravenous + intralesional	Acute, intermediate and chronic (6-15 months)	9	AIS A: 10, AIS B: 2, AIS C: 3	No serious adverse effects
Zhao et al[76], 2017	N/A	8	Cervical (4) and thoracic (4)	AIS A	Allogeneic neonatal umbilical cord tissue	UCMSC	4 × 107	Scaffold	Intermediate and chronic (max 36 months)	12	Expansion of sensation level (62.5%) and expansion of the MEP-responsive area (87.5%) but AIS=	No serious adverse effects
Xiao et al[77], 2018	I	2	Cervical and thoracic	AIS A	Allogeneic	UCMSC+ Scaffold	40 × 106	Intramedullary	Acute	12	AIS A→C in both patients	No serious adverse effects
Deng et al[72], 2020	I	20	Cervical	AIS A	Allogeneic	UCMSC+ Scaffold	40 × 106 (Collagen scaffold)	Intramedullary	Acute	12	AIS A→B (9 patients), AIS A→C (2 patients). Improvement in ADL scores. Improvement in bowel and bladder function	No serious adverse effects
Albu et al[31], 2021	I/IIa	10	Thoracic	AIS A	Allogeneic	WJ-MSC	10 × 106	Intrathecal	Chronic	6	Significant improvement in pinprick sensation in compared with placebo group. No changes in motor function, independence, QoL, SEPs, MEPs, spasticity or bowel function	No serious adverse effects
Yang et al[23], 2021	I/II	102	Cervical, thoracic and lumbar	ASIA score: 158.15 ± 70.93, IANR-SCIFRS total score: 24.54 ± 9.82	Allogeneic neonatal umbilical cord tissue	UCMSC	1 × 106/kg	Intrathecal	Intermediate and chronic (max 240 months)	12	ASIA score: 183.88 ± 69.76, IANR-SCIFRS total score: 29.49 ± 10.47	No serious adverse effects. Fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%)
Zhao et al[78], 2021	N/A	7	Cervical (3) and thoracic (4)	ASIA pin prick: 55.00 ± 28.46, ASIA light touch: 55.00 ± 28.46, ASIA motor score: 42.00 ± 28.19	Allogeneic neonatal umbilical cord tissue	UCMSC	5 × 104	Intrathecal	Intermediate and chronic (max 60 months)	6	ASIA pin prick: 57.06 ± 30.01, ASIA light touch: 58.20 ± 29.36, ASIA motor score: 44.13±27.23	No serious adverse effects
Smirnov et al[16], 2022	I/IIa	10	Cervical, thoracic and lumbar	AIS A: 6, AIS B: 4	Allogeneic	HUCBC	14.8 × 106/kg (Total cell number for 4 infusions)	Intravenous	Acute	12	AIS A→C: 3, AIS B→D: 2, AIS B→E: 2, AIS A→D: 1	No serious adverse effects related to therapy

Time from injury: Immediate: 0 - 2 h after the injury; acute: Early acute phase: 2 - 48 h; subacute: 2 d - 2 wk; intermediate: 2 wk - 6 months; chronic phase: > 6 months. AIS: American spinal injury association Impairment Scale; HESC: Human embryonic stem cells; HUCBC: human umbilical cord blood mononuclear cells; UCMSC: Umbilical cord derived mesenchymal stem cells; WJ-MSC: Wharton's jelly-Mesenchymal stem cells.