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

Table 5 Summary of the studies included in the systematic literature review focusing on nervous tissue derived stem cells (i.e., NSC, huCNSSC, OEC)

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
Shin et al[47], 2015	I/IIa	19	Cervical	AIS A: 17, AIS B: 2	Human fetal brain	NSC	1 × 108	Intralesional	Acute and intermediate	12	AIS A→C: 2, AIS A→B: 1, AIS B→D: 2; AIS=: 14. Positive response in SSEP (35.3%) and MEP (58.8%) activities of AIS-A patients below the level of injury	No serious adverse effects
Ghobrial et al[65], 2017	II	5	Cervical	AIS A: 1, AIS B: 4	Allogeneic fetus	huCNSSC®	15-40 × 106	Intrathecal	Chronic	12	AIS A→B: 1, AIS B→A: 1, AIS=: 3, GRASSP score mean improvement: 14.8 ± 7.8, ISNCSCI score mean improvement: 17.3 ± 16.8	No serious adverse effects
Anderson et al[66], 2017	I	6	Thoracic	N/A	Autologous (sural nerve)	SC	5, 10 or 15 × 106	Intramedullary	Subacute	12	AIS A→B: 1. Improvement in FIM and SCIM III scores	No serious adverse effects
Levi et al[67], 2018	I/II	29	Cervical: 17 (Cohort I: 6, Cohort II: 11) Thoracic: 12	AIS A: 11, AIS B: 18	Allogeneic (Stemcells Inc.)	huCNSSC®	15 − 40 × 106	Intramedullary	Subacute	Up to 56	Improvement in AIS motor scores	15 serious adverse effects in cervical group and 4 in thoracic
Curtis et al[68], 2018	I	4	Thoracic	AIS A	Allogeneic (human-spinal-cord-derived neural stem cell)	NSI-566®	6 injections (Mean number)	Intramedullary	Chronic	60	Improved AIS scores, neurological levels and EMG findings. No improvement in QoL	No serious adverse effects
Levi et al[69], 2019	I/II	17 Cohort I: 6, Cohort II: 11 6/11 monitored	Cervical	AIS A, B	Allogeneic (Stemcells Inc.)	huCNSSC®	15 + 30 + 40 × 106 (Coh.I) 40 × 106 (Coh.II)	Intramedullary	Intermediate or Chronic (max 24 months)	12	Improvement in UEMS score	No serious adverse effects
Curt et al[70], 2020	I/IIa	12	Thoracic	AIS A: 7, AIS B: 5	Allogeneic (Stemcells Inc.)	huCNSSC®	20 × 106	Intramedullary	Intermediate or chronic (max 24 months)	72	Sensory improvements in 5 out of 12 patients. No motor improvements were observed	N No serious adverse effects
Zamani et al[71], 2021	I	3	Thoracic	AIS A	Autologous	OEC+ BMSC	15 × 106, OEC/BMSC = 1/1	Intrathecal	Chronic	24	AIS A→B: 1 and 6 points improvement in SCIM	Mild adverse effects
Gant et al[72], 2022	I	8	Cervical: 4; Thoracic: 4	N/A	Autologous (sural nerve)	SC	50 − 200 × 106	Intramedullary	Chronic	60	The neurological level improved by 1 level in 1 patient. Improvement in Sensory score in all patients with thoracic and in 2 patients with cervical lesion	No serious adverse effects

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; BMSC: Bone Marrow Mesenchymal Stromal Cells; EMG: Electromyography; MSC; Mesenchimal stem cell; NSC: Neural stem cells; OEC: Olfactory ensheathing cell; SC: Stem cell; SCIM: Spinal cord independence measure.