Reprogramming of skin fibroblasts by 3D spheroid culture promotes peripheral nerve regeneration via the ID3/semaphorin7a pathway

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Peripheral nerve injury remains an intractable clinical issue with high morbidity, causing an excessive burden on the economy and society. Peripheral nerve tissue engineering combined with nerve conduits and supporting seed cells is considered a promising strategy for treating of long nerve defects. However, supporting seed cell sources that are easily accessible, capable of rapid expansion, and do not require genetic intervention are still urgently needed. This study intended to clarify whether the easily accessible and rapid expansion skin fibroblasts are the ideal supporting seed cells and can be reprogrammed into neural progenitor-like cells (NPCs) by forcing them to grow into a three-dimensional (3D) spheroid morphology. Results showed that 3D spheroid mouse dermal fibroblasts (MDFs) exhibited neural cell-like properties and could efficiently induce dorsal root ganglion neurons to extend the neurites. Transplantation of 3D spheroid MDFs significantly accelerated the regeneration of the sciatic nerve and improved the motor function of rats after transection compared to monolayer MDFs. Mechanism studies revealed that 3D spheroid culture significantly upregulated the expressions of the inhibitor of DNA binding 3 (ID3) and the hypoxia-inducible factor-1α (HIF-1α). The upregulation of the inhibitor of DNA binding 3 in 3D spheroid MDFs plays a critical role in acquiring NPC prop

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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