Comparative analysis of key factors in the selected clinical studies

Delivery methodsStudyStudy typeStudy populationNo. of casesNIHSS score rangeSource of stem cellsNo. of injected cellsTime point of administrationDuration of follow-upImprovement of observation indicatorsExperimental constraints
Systemic deliveryBang et al. [3]Randomized, controlled, early phase II clinical trial30–75 y.o.; MCA stroke57–14Autologous; BM50 million; two timesAt 32–41 days52 weeksHigher BI; lower mRS and NIHSSSmall sample size
MASTERS-1 [4]Randomized, double-blind, placebo-controlled, phase II clinical trial18–83 y.o.; AIS678–20Allogeneic; BM400/1,200 millionat 24–48 h12 monthsHigher BI; lower mRS and NIHSSSmall 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.; AISRecruitingData not includedAllogeneic1.2 billionat 18–36 h365 daysOngoingData not included
J-REPAIR [6]Randomized, double-blind, placebo-controlled, multicentre, early phase II clinical trial≥ 20 y.o.; anterior circulation AIS425–20Allogeneic; dental pulp100/300 millionwithin 48 h366 daysOngoingSmall sample size; proof-of-concept study-further studies required
Law et al. [7]Randomized, assessor-blinded, controlled, single-center, phase II clinical trial30–75 y.o.; MCA stroke910–35Autologous; BM2 million/kg body weightwithin 2 months12 monthsNo difference with control groupSmall sample size
STARTING-2 [8, 9, 12]Randomized, prospective, open-label, controlled trial30–75 y.o.; MCA stroke396–21Autologous; BM1 million/kg body weightwithin 90 days3 monthsNo difference with control groupSmall 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.; AIS48–20Autologous; AD1 million/kg body weightwithin 2 weeks24 monthsLess AEs; lower NIHSSSmall sample size
Direct in loco injectionPISCES-2 [14]Prospective, open-label, single-arm, multicentre study> 40 y.o.; upper limb motor deficit after AIS23Arm score 2–4Allogeneic; neural20 millionat 2–13 months12 monthsImproved ARAT in 7 patients; BI in 8; mRS in 7Small sample size; lack of control group; open-label design
PASSIoN [15]First-in-human, open-label, single-arm, single-center, early phase II, intervention studyNeonates (full-term) with MCA PAIS10Data not includedAllogeneic; BM45/50 millionwithin 7 days3 monthsImprovements in pre-Wallerian changes to corticospinal tracts in 60% of patientsSmall sample size; lack of control group; short follow-up duration
Dehghani et al. [16]Randomized, prospective, single-center, pilot clinical trialMalignant MCA stroke; decompressive craniectomy candidates511–25Allogeneic; placenta-derived exosomes2 mL (356 µg/mL)within 48 h3 monthsDecreased mRS and NIHSS in 4 patientsSmall 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