Table 2.
Selected recent preclinical studies using cell therapy for stroke
| Route | Cell source | Ischaemia | Species | Animals, n | Sex | Stroke phase | Dose | Major findings | Year |
|---|---|---|---|---|---|---|---|---|---|
| IP | iPSC-NSC171 | Permanent | Mouse | 40 | Male and female | Chronic | 2.5 × 105 | Improved angiogenesis, reduced inflammation, axonogenesis, reduced BBB leakage, improved functional outcome | 2024 |
| IP | iPSC-organoids161 | Permanent injury on visual cortex | Rat | 36 | Male | Chronic | Organoids | Survival, differentiation, neuronal projections to visual system and spontaneous and visually-evoked neural activity of engrafted organoid cells (GFP, IHC, rabies virus retrograde tracing, herpes simplex virus anterograde tracing, electrophysiological recordings) | 2023 |
| IP | Human brain-derived iSCs191 | Permanent | Mouse | 118 | N/A | Chronic | 1.0 × 104 | Improved behavioural recovery (wire hang, basket, open-field, hot plate, Y-maze, passive avoidance-learning, sucrose preference and tail suspension tasks); homing and differentiation of engrafted cells (GFP, IHC); activation of endogenous NSCs (IHC) | 2023 |
| 1.0 × 105 | |||||||||
| IP | NSC19 | Temporary | Mouse | 75 | Male | Subacute | 1.0 × 105 | Reduced infarct size (TTC); reduced inflammation TNFα, IL6, IL1β, ICAM1 and extracellular matrix disassembly MMP3, MMP9 (PCR); brain transcriptome (bulk RNAseq) | 2022 |
| IP | Glia-enriched progenitors18 | Temporary | Mouse | 114 | Male | Acute–chronic | 0.9 × 105 | Reduced infarct size (BDA); improved behavioural recovery (grid walking, cylinder test, novel object recognition, fear conditioning); homing, survival, proliferation and differentiation of engrafted cells (GFP, IHC); improved axon growth and connection (BDA, IHC); improved remyelination and oligodendrocyte proliferation (IHC) | 2021 |
| IP | Control and p5-primed ADMSCs23 | Temporary | Rat | 40 | Male | – | 1.0 × 106 | No change in infarct volume (IHC NeuN); improved behavioural recovery (beam walking, sticky-tape, cylinder test, water maze); reduced microglia apoptosis (IHC, p5-ADMSCs only); increased angiogenesis (IHC); survival of engrafted cells (IHC) |
2021 |
| IA | MSCs20 | Temporary | Rat | 30 | Female | Acute | 1.0 × 105 | Reduced infarct volume (TTC); improved behavioural recovery (NDS, Rotarod); reduced brain inflammasome activity caspase 1, ASC, IL1β, ASIC1a, NLRP1, NLRP3 (WB) | 2021 |
| IV | hPSC-pericytes29 | Temporary | Mouse | 110 | Male | Subacute | 1.0 × 106 | Reduced infarct size (TTC); improved behavioural recovery (NDS, corner test, sticky-tape, Rotarod); reduced neuron apoptosis (TUNEL, IHC); improved BBB (water content, permeability assay, TEM, WB, IHC); homing, vessel investment and pericytic differentiation of engrafted cells (DsRedE2, IHC); greater benefits by hPSC-PC than fibroblast, similar to brain pericyte; the role of midline in neuroprotection by hPSC-PC | 2020 |
Stroke phase at time point of cell transplantation: acute, <1 day; subacute, 1 day–7 days; chronic, >7 days. Animal numbers in some studies were estimated based on the methods section and figure legends. ADMSCs = adipose-derived mesenchymal stem cell; BBB = blood–brain barrier; BDA = biotinylated dextran amine; fMRI = functional MRI; IA = intra-arterial; IP = intraparenchymal; IHC = immunohistochemistry; iPSCs = Induced pluripotent stem cells; iSC = induced multipotent stem cells; IV = intravenous; MSCs = marrow stromal cells; NDS = neurologic deficit score; NPCs = neural progenitor cells; NSCs = neural stem cells; TTC = 5-triphenyltetrazolium chloride staining; WB = western blot.