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  4. Stepwise combined cell transplantation using mesenchymal stem cells and induced pluripotent stem cell-derived motor neuron progenitor cells in spinal cord injury

Stepwise combined cell transplantation using mesenchymal stem cells and induced pluripotent stem cell-derived motor neuron progenitor cells in spinal cord injury

Stem Cell Research & Therapy, 2024 · DOI: https://doi.org/10.1186/s13287-024-03714-3 · Published: April 2, 2024

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

Spinal cord injuries often lead to permanent loss of function due to nerve damage. Stem cell therapy offers a promising neuroregeneration strategy. This study investigates the effectiveness of combined human mesenchymal stem cells (hMSC) and induced pluripotent stem cell (iPSC)-derived motor neuron progenitor cells (iMNP) in rats with spinal cord injury. The researchers induced neurite outgrowth by co-culturing hMSC and iPSC-derived motor neurons (iMN) in both 2D and 3D platforms. They found that combined cell therapy improved behavioral recovery and was more effective than using single cell therapy alone. In vitro results showed that hMSC and iMN worked together synergistically to promote neurite outgrowth during iMN differentiation. The study demonstrates that stepwise combined cell therapy can alter the microenvironment to facilitate effective cell therapy for spinal cord injuries. The in vitro results further support the idea that co-culturing hMSC and iMN can synergistically promote motor neuron neurite outgrowth induction.

Study Duration
Not specified
Participants
Sprague-Dawley rats
Evidence Level
Not specified

Key Findings

  • 1
    Stepwise combined cell therapy can induce alterations in the microenvironment for effective cell therapy in SCI.
  • 2
    Stepwise combined cell therapy promoted mature motor neuron differentiation and axonal regeneration at the lesional site.
  • 3
    Stepwise combined cell therapy significantly improved behavioral recovery in rat models of SCI compared to single-cell therapy.

Research Summary

This study investigates the efficacy of transplanted cells using stepwise combined cell therapy with human mesenchymal stem cells (hMSC) and induced pluripotent stem cell (iPSC)-derived motor neuron progenitor cells (iMNP) in a rat model of SCI. Stepwise combined cell therapy promoted mature motor neuron differentiation and axonal regeneration at the lesional site. In addition, stepwise combined cell therapy improved behavioral recovery and was more effective than single cell therapy alone. Our study demonstrated that stepwise cell therapy increased MN differentiation and axonal regeneration compared to single-cell therapy in severed SCI model. Stepwise cell therapy increased behavioral recovery and the rate of BBB locomotor scale grade 3 (BBB score, 10–15).

Practical Implications

Clinical Translation

The stepwise combined cell transplantation strategy suggests ideal stem cell selection for each stage of SCI, confirming the function of the transplanted cells.

Therapeutic Efficacy

Stepwise combined cell transplantation shows therapeutic efficacy in a severed contusion SCI rat model by restoring clinical behavioral outcomes.

Neuroregeneration

Multiple preemptive hMSC injections in the acute SCI phase can enhance MN differentiation and maturation at the lesional site.

Study Limitations

  • 1
    The lack of an explanation for the mechanisms underlying the synergistic effect of stepwise combined cell transplantation in a contusion SCI model.
  • 2
    The study had a limitation in that few animals were used due to the pilot study concept (Subtopic 1).
  • 3
    There is a need to overcome the limitations of stem cell therapy for SCI using a stepwise combined cell transplantation strategy with a 3D iPSC-derived motor neuron source.

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