Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats

International Journal of Molecular Sciences, 2020 · DOI: 10.3390/ijms21249593 · Published: December 16, 2020

Simple Explanation

Amyotrophic lateral sclerosis (ALS) is a complex, progressive neurodegenerative disorder, causing general muscle weakness, atrophy, and palsy, leading to eventual respiratory failure and death. Neural progenitors derived from induced pluripotent cells (NP-iPS) might rescue or replace dying motoneurons (MNs). NP-iPS transplantation signiﬁcantly preserved MNs, slowed disease progression, and extended the survival of all treated animals.

Study Duration

Not specified

Participants

88 rats, SOD1 and wild type (WT)

Evidence Level

Not specified

Key Findings

1
NP-iPS transplantation signiﬁcantly preserved MNs, slowed disease progression, and extended the survival of all treated animals.
2
NP-iPS application led to normalized host genes expression (versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3) and the protection of perineuronal nets around the preserved MNs.
3
In the host spinal cord, transplanted cells remained as progenitors, many in contact with MNs, but they did not diﬀerentiate.

Research Summary

The ﬁndings suggest that NP-iPS demonstrate neuroprotective properties by regulating local gene expression and regulate plasticity by modulating the central nervous system (CNS) extracellular matrix such as perineuronal nets (PNNs). The grafted cells had a limited survival time after transplantation, and by the end of the experiment (2.5 months after administration in the symptomatic group and 5 months after administration of the pre-symptomatic group), surviving NP-iPS cells were only seen in the late-grafted animals. Taken together, our results show that NP-iPS cells transplanted into SOD-1 rats can surround motoneurons, protect them from degeneration, and preserve motor function.

Practical Implications

Therapeutic Potential

Stem cell and progenitor therapy can modify the progression of neurodegenerative pathology, suggesting new avenues for ALS treatment.

Combination Therapies

Combining NP-iPS therapy with drugs that prevent PNN loss or block MIF interaction could enhance therapeutic efficacy for ALS and other neurodegenerative diseases.

Paracrine Effects

The paracrine effects of NP-iPS, similar to MSCs, indicate that neuroprotection is achieved through secreted factors rather than cell differentiation into mature neuronal phenotypes.

Study Limitations

1
The implanted cells did not diﬀerentiate into MNs, but they remained undiﬀerentiated.
2
The cell fate is most likely dependent on the neural progenitor phenotype.
3
Since we did not inject WT animals with NP-iPS, it is diﬃcult to interpret whether low cell survival is due to SOD1-mutated environment or not.

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