Implantation of olfactory ensheathing cells promotes neuroplasticity in murine models of stroke

The Journal of Clinical Investigation, 2008 · DOI: 10.1172/JCI34363 · Published: July 1, 2008

Simple Explanation

The study investigates the potential of human olfactory ensheathing cells/olfactory nerve fibroblasts (hOECs/ONFs) to improve neurological dysfunction caused by hypoxic/ischemic stress in murine models of stroke. These cells secrete trophic factors, including stromal cell–derived factor–1α (SDF-1α), which are believed to promote neuroplasticity. Transplantation of hOECs/ONFs into rats with stroke led to improved behavioral measures and increased glucose metabolic activity in the brain, as shown by FDG-PET. This suggests enhanced brain function and recovery. The transplanted hOECs/ONFs also appeared to stimulate endogenous stem cells, including neural progenitor cells and bone marrow stem cells, to migrate to the damaged brain area and enhance neuroplasticity. This process involves the upregulation of SDF-1α and its interaction with CXCR4 and cellular prion protein (PrPC).

Study Duration

Not specified

Participants

Rats and mice

Evidence Level

Level 2; Animal Studies

Key Findings

1
hOECs/ONFs secrete trophic factors, including SDF-1α, and upregulate CXCR4 under oxygen glucose deprivation (OGD) conditions, promoting neurite outgrowth of primary cortical neurons.
2
hOEC/ONF transplantation improves neurological dysfunction after cerebral ischemia in rats, as indicated by reduced body asymmetry, increased locomotor activity, and enhanced grip strength.
3
hOEC/ONF implantation stimulates endogenous stem cell mobilization, homing, and engraftment into the rat brain following cerebral ischemia, contributing to neural regeneration.

Research Summary

This study demonstrates that human olfactory ensheathing cells/olfactory nerve fibroblasts (hOECs/ONFs) promote neuroplasticity in murine models of stroke by secreting trophic factors and upregulating CXCR4. Transplantation of hOECs/ONFs leads to improved neurological function, enhanced glucose metabolic activity, and stimulation of endogenous stem cell mobilization and engraftment in the ischemic brain. The neuroplastic effects of hOECs/ONFs are mediated by the upregulation of SDF-1α and the enhancement of CXCR4 and PrPC interaction, suggesting a potential clinical benefit of autologous transplantation in stroke patients.

Practical Implications

Potential Therapeutic Application

hOECs/ONFs may be used as a potential therapeutic approach for stroke patients through autologous transplantation to promote neuroplasticity and functional recovery.

Stem Cell Mobilization

hOEC/ONF transplantation can stimulate endogenous stem cell mobilization and homing to the site of injury, enhancing regenerative processes in the brain.

Drug Target Identification

The SDF-1α/CXCR4/PrPC pathway can be further explored as a potential drug target to enhance neuroprotection and neurite regeneration in ischemic conditions.

Study Limitations

1
The study is conducted in murine models, and the results may not be directly translatable to human stroke patients.
2
The exact mechanisms of cell fusion between hOECs/ONFs and endogenous stem cells need further investigation.
3
Long-term effects and potential adverse events of hOEC/ONF transplantation were not evaluated.

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