# Stem cell therapy for ischemic stroke: neuroimaging approaches and evidence from a systematic review

**Authors:** Bin Jiang, Moss Zhao, Elizabeth Tong, Yongkai Liu, Ates Fettahoglu, Wen-Kai Weng, Michael E. Moseley, Max Wintermark, Gary K. Steinberg, Greg Zaharchuk

PMC · DOI: 10.3389/fneur.2026.1718086 · Frontiers in Neurology · 2026-02-10

## TL;DR

This paper reviews how neuroimaging can assess stem cell therapy for ischemic stroke, finding some trends in recovery but highlighting the need for standardized methods.

## Contribution

The paper provides a systematic review and meta-analysis of neuroimaging outcomes in stem cell therapy for stroke, emphasizing the need for standardized protocols.

## Key findings

- Meta-analysis showed no significant infarct volume reduction in subacute stroke patients after stem cell therapy.
- Chronic stroke patients showed less volume loss and trends toward improved white matter recovery and motor cortex activity.
- SPIO-labeled stem cells were safe, with T2* imaging showing engraftment and migration.

## Abstract

Cell-based therapy is a promising approach for ischemic stroke treatment. This systematic review and meta-analysis aimed to consolidate clinical evidence on the use of neuroimaging to evaluate stem cell therapy across all stages of stroke recovery.

A systematic search was conducted in 5 databases in July 2025. They were included if neuroimaging analysis, regardless of cell source, route administration or dosage were reported. The level of evidence and risk of bias were assessed using the ROB-2 or ROBINS-I tool. Imaging data from all included articles were extracted, and randomized-effect meta-analyses were performed when two or more outcomes were available for any reported imaging parameter.

Thirty articles were included in the systematic review, of which four were eligible for meta-analysis. Meta-analysis of subacute stroke patients revealed no significant differences in infarct volume reduction at 3 months (SMD = −0.50; 95% CI: −1.15 to 0.51; p = 0.13; I2 = 63%) or 1 year (SMD = −1.02; 95% CI: −3.63 to 1.60; p = 0.45; I2 = 92%) between treatment and control group. Chronic stroke patients exhibited less overall volume loss. There was a trend toward improved white matter recovery and motor cortex activity, reflected in increased DTI and fMRI parameters. SPIO-labeled autologous stem cells recently proved safe in patients, with T2* imaging showing engraftment and migration.

Advanced neuroimaging offers a valuable non-invasive tool for assessing the effects of stem cell therapy in ischemic stroke. However, substantial heterogeneity in imaging protocols and reporting limits cross-study comparisons. Standardization of neuroimaging methodology is essential to advance future research and clinical translation.

## Linked entities

- **Diseases:** ischemic stroke (MONDO:1060198)

## Full-text entities

- **Genes:** CEBPZ (CCAAT enhancer binding protein zeta) [NCBI Gene 10153] {aka CBF, CBF2, HSP-CBF, NOC1}, CST12P (cystatin 12, pseudogene) [NCBI Gene 106478911] {aka Cst, Ctes4, E2}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** volume loss (MESH:D016388), hematoma (MESH:D006406), long-term disability (MESH:D000088562), spasticity (MESH:D009128), inflammatory (MESH:D007249), death (MESH:D003643), ischemic stroke (MESH:D002544), hemorrhagic stroke (MESH:D000083302), neuroinflammation (MESH:D000090862), Infarct (MESH:D007238), cerebellar diaschisis (MESH:D000087505), hemorrhage (MESH:D006470), vasogenic edema (MESH:D001929), Chronic stroke (MESH:D020521), sickle cell (MESH:D000755), moyamoya diseases (MESH:D009072), ventricle (MESH:D002551), neurological deficits (MESH:D009461), ROBINS-I (MESH:C580335), tissue damage (MESH:D017695)
- **Chemicals:** 15O]H2O (-), oxygen (MESH:D010100), N-acetylaspartate (MESH:C000179), 18F-fluorodeoxyglucose (MESH:D019788), iron (MESH:D007501), SPIO (MESH:C000499), FA (MESH:D005492)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** NT2/D1 — Homo sapiens (Human), Embryonal carcinoma, Cancer cell line (CVCL_3407), LBS-Neuron — Homo sapiens (Human), Transformed cell line (CVCL_E751), CTX0E03 — Homo sapiens (Human), Conditionally immortalized cell line (CVCL_9T00), SB623 — Canis lupus familiaris (Dog), Canine hemangiosarcoma, Cancer cell line (CVCL_0C95), NSI-566 — Mus musculus (Mouse), Mouse multiple myeloma, Cancer cell line (CVCL_2155)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12931286/full.md

## References

63 references — full list in the complete paper: https://tomesphere.com/paper/PMC12931286/full.md

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Source: https://tomesphere.com/paper/PMC12931286