Comparative analysis of key factors in the selected clinical studies
| Delivery methods | Study | Study type | Study population | No. of cases | NIHSS score range | Source of stem cells | No. of injected cells | Time point of administration | Duration of follow-up | Improvement of observation indicators | Experimental constraints |
| Systemic delivery | Bang et al. [3] | Randomized, controlled, early phase II clinical trial | 30–75 y.o.; MCA stroke | 5 | 7–14 | Autologous; BM | 50 million; two times | At 32–41 days | 52 weeks | Higher BI; lower mRS and NIHSS | Small sample size |
| MASTERS-1 [4] | Randomized, double-blind, placebo-controlled, phase II clinical trial | 18–83 y.o.; AIS | 67 | 8–20 | Allogeneic; BM | 400/1,200 million | at 24–48 h | 12 months | Higher BI; lower mRS and NIHSS | Small sample size; expansion of time window from 24–36 h to 24–48 h | |
| MASTERS-2 [4] | Randomized, phase III clinical trial | ≥ 18 y.o.; AIS | Recruiting | Data not included | Allogeneic | 1.2 billion | at 18–36 h | 365 days | Ongoing | Data not included | |
| J-REPAIR [6] | Randomized, double-blind, placebo-controlled, multicentre, early phase II clinical trial | ≥ 20 y.o.; anterior circulation AIS | 42 | 5–20 | Allogeneic; dental pulp | 100/300 million | within 48 h | 366 days | Ongoing | Small sample size; proof-of-concept study-further studies required | |
| Law et al. [7] | Randomized, assessor-blinded, controlled, single-center, phase II clinical trial | 30–75 y.o.; MCA stroke | 9 | 10–35 | Autologous; BM | 2 million/kg body weight | within 2 months | 12 months | No difference with control group | Small sample size | |
| STARTING-2 [8, 9, 12] | Randomized, prospective, open-label, controlled trial | 30–75 y.o.; MCA stroke | 39 | 6–21 | Autologous; BM | 1 million/kg body weight | within 90 days | 3 months | No difference with control group | Small sample size; open-label design; short follow-up duration | |
| AMASCIS [10] | Randomized, double-blind, placebo-controlled, single-center, phase IIa pilot clinical trial | ≥ 60 y.o.; AIS | 4 | 8–20 | Autologous; AD | 1 million/kg body weight | within 2 weeks | 24 months | Less AEs; lower NIHSS | Small sample size | |
| Direct in loco injection | PISCES-2 [14] | Prospective, open-label, single-arm, multicentre study | > 40 y.o.; upper limb motor deficit after AIS | 23 | Arm score 2–4 | Allogeneic; neural | 20 million | at 2–13 months | 12 months | Improved ARAT in 7 patients; BI in 8; mRS in 7 | Small sample size; lack of control group; open-label design |
| PASSIoN [15] | First-in-human, open-label, single-arm, single-center, early phase II, intervention study | Neonates (full-term) with MCA PAIS | 10 | Data not included | Allogeneic; BM | 45/50 million | within 7 days | 3 months | Improvements in pre-Wallerian changes to corticospinal tracts in 60% of patients | Small sample size; lack of control group; short follow-up duration | |
| Dehghani et al. [16] | Randomized, prospective, single-center, pilot clinical trial | Malignant MCA stroke; decompressive craniectomy candidates | 5 | 11–25 | Allogeneic; placenta-derived exosomes | 2 mL (356 µg/mL) | within 48 h | 3 months | Decreased mRS and NIHSS in 4 patients | Small sample size; short follow-up duration |
y.o.: years old; BI: Barthel index; mRS: modified Rankin scale; AIS: acute ischemic stroke; AD: adipose tissue-derived