Three Growth Factors Induce Proliferation and Differentiation of Neural Precursor Cells In Vitro and Support Cell-Transplantation after Spinal Cord Injury In Vivo

Stem Cells International, 2020 · DOI: https://doi.org/10.1155/2020/5674921 · Published: June 17, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Stem cell therapy using neural precursor cells (NPCs) shows promise for improving nerve regeneration after spinal cord injuries. However, the survival and specialization of these transplanted cells within the injured spinal cord is often limited. This study investigates whether using a smaller number of growth factors, in various combinations, can boost the multiplication and specialization of NPCs in a lab setting. The research team identified a specific combination of growth factors (EGF, bFGF, and PDGF-AA) that encourages the cells to develop into oligodendrocytes and neurons, while reducing their development into astrocytes. Following this in vitro work, the team tested their findings in rats with spinal cord injuries, using NPC transplantation and growth factor administration. The results showed that the transplanted NPCs survived in the injured animals and mainly turned into oligodendrocytes and their precursors. Additionally, the rats showed improvements in their walking abilities. The study suggests that using just EGF, bFGF, and PDGF-AA is enough to support NPC transplantation.

Study Duration

8 weeks

Participants

24 female Wistar rats

Evidence Level

Level II: Animal study

Key Findings

1
A growth factor cocktail (EGF, bFGF, and PDGF-AA) increased NPC proliferation and directed cell fate towards the oligodendroglial and neuronal lineage while reducing astrocytic diﬀerentiation in vitro.
2
NPC transplantation with the three growth factors in vivo led to verifiable survival of the transplanted NPCs in the chronic phase 8 weeks after injury.
3
Functional recovery was partially increased with NPC transplantation and administration of the growth factors, possibly related to decreased posttraumatic inﬂammation and apoptotic cell death in the injured spinal cord.

Research Summary

This study aimed to identify a cost-effective combination of growth factors to improve NPC survival and differentiation in vitro and in vivo after spinal cord injury (SCI). A combination of EGF, bFGF, and PDGF-AA was found to promote NPC proliferation and differentiation towards oligodendrocytes and neurons while reducing astrocyte differentiation in vitro. This cocktail also supported NPC survival and differentiation in a rat SCI model. The study suggests that this reduced three-growth factor cocktail is sufficient to support NPC transplantation into the hostile post-injury environment, offering a more practical approach for potential clinical translation.

Practical Implications

Reduced Cost of Treatment

The finding that a cocktail of only three growth factors (EGF, bFGF, and PDGF-AA) is sufficient for NPC transplantation could significantly reduce the cost associated with stem cell therapies for spinal cord injury.

Improved Clinical Translation

The use of a smaller number of growth factors makes the treatment more practical and feasible for translation into clinical practice, potentially bringing stem cell therapy closer to becoming a mainstream treatment option for SCI.

Targeted Cell Differentiation

The ability to direct NPC differentiation towards oligodendrocytes and neurons while limiting astrocyte differentiation could lead to better functional outcomes after SCI, as oligodendrocytes are crucial for remyelination and neuronal regeneration.

Study Limitations

1
The effects observed on locomotor regeneration are still low.
2
The surviving NPC-graft might be too small.
3
Synergistic treatment approaches helping to promote neuronal diﬀerentiation might be necessary to further improve functional recovery after cervical SCI.

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