Embryonic stem cells overexpressing high molecular weight FGF2 isoform enhance recovery of pre-ganglionic spinal root lesion in combination with fibrin biopolymer mediated root repair

Stem Cell Research & Therapy, 2024 · DOI: https://doi.org/10.1186/s13287-024-03676-6 · Published: February 21, 2024

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This study investigates a new approach for treating severe nerve damage in the spinal cord using stem cells. Specifically, it looks at how different versions of a growth factor (FGF2) produced by human embryonic stem cells (hESCs) can help repair damaged nerve roots when combined with a special biological glue (HFB). The researchers found that stem cells modified to produce a specific type of FGF2 (the 31 kD isoform) were the most effective at protecting nerve cells and improving recovery in rats with spinal cord injuries. This treatment helped the damaged nerves reconnect and reduced harmful inflammation. These findings suggest that using stem cells to deliver growth factors directly to the injury site could be a promising way to treat spinal cord damage in humans, potentially leading to better outcomes for patients with these types of injuries.

Study Duration

12 weeks

Participants

95 adult female Lewis rats

Evidence Level

Not specified

Key Findings

1
hESCs overexpressing the 31 kD isoform of FGF2 showed superior neuroprotective effects compared to other isoforms and wild-type hESCs after ventral root avulsion.
2
The 31 kD FGF2 - hESC therapy enhanced both motor and sensory recovery in rats with spinal root avulsion and reimplantation, as evidenced by improved gait parameters and nociceptive thresholds.
3
The 31 kD FGF2 - hESC treatment modulated glial response, particularly by controlling reactive astrogliosis, and promoted the preservation of inhibitory synaptic inputs while mitigating the sprouting of glutamatergic boutons.

Research Summary

The study compared the efficacy of different FGF2 isoforms (18, 23, and 31 kD) overexpressed in hESCs for treating spinal ventral root avulsion in rats, using HFB for root repair. The 31 kD isoform showed the best neuroprotective and regenerative properties. Engraftment of hESCs expressing the 31 kD FGF2 isoform led to significant neuroprotection, immunomodulation, attenuation of astrogliosis, and preservation of inputs to rescued motoneurons. Behaviorally, this therapy enhanced both motor and sensory recovery. Transgenic hESCs served as an effective delivery platform for neurotrophic factors, rescuing axotomized motoneurons and modulating glial response after proximal spinal cord root injury. This approach shows promise for spinal cord repair and potential clinical translation.

Practical Implications

Therapeutic Potential

The use of bioengineered hESCs overexpressing 31 kD FGF2 presents a promising therapeutic strategy for spinal cord injuries, particularly those involving plexus lesions.

Clinical Translation

The study's findings provide a basis for further investigation and potential clinical translation of stem cell therapy for spinal cord repair.

Targeted Neuroprotection

Targeting reactive astrogliosis and promoting inhibitory synaptic inputs through FGF2-modified hESCs can improve functional outcomes after spinal cord injury.

Study Limitations

1
The study was conducted on rats, and results may not directly translate to humans.
2
The long-term effects of hESC therapy and potential immune responses require further investigation.
3
The precise molecular mechanisms underlying the neuroprotective effects of 31 kD FGF2 - hESCs need further elucidation.

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