Getting it right before transplantation: example of a stem cell model with regenerative potential for the CNS

Frontiers in Cell and Developmental Biology, 2014 · DOI: 10.3389/fcell.2014.00036 · Published: August 13, 2014

Simple Explanation

The paper discusses using human embryonic stem cells (hESCs) to generate neural precursors (NPs) for potential therapies for neurodegenerative diseases. It emphasizes the importance of characterizing these NPs thoroughly before transplantation to ensure their safety and efficacy. The authors share their experience with the CCTL14 hESC line, detailing methods for differentiation, characterization, and transplantation assays.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
hESC-derived NPs can exhibit spontaneous and evoked activity, indicating their electrophysiological and calcium handling properties are similar to matured neurons.
2
Functional characterization of hESC-derived NPs reveals the expression of voltage-gated Na+ channels, A-type K+ current, outwardly rectifying K+ current, and GABA-evoked currents.
3
Transplantation assays show that hESC-derived NPs (passage 8) have elevated survival, low tumor formation, and capacity of cell migration toward the lesion site in rat brains after stroke injury.

Research Summary

This perspective article examines neuronal differentiation and the characterization of neural progenitors derived from human embryonic stem cells for neural regeneration. The authors present a cell model that was successfully used in functional analyses and engraftment experiments, highlighting the importance of thorough characterization before transplantation. The review emphasizes the need for a unified international system to register human stem cell lines and highlights the challenges in characterizing these novel cell lines.

Practical Implications

Improving Neural Regeneration

The summarized information serves as a basis to design better stem cell-based therapies to improve neural regeneration.

Drug Screening and Cell Therapy

Cells, such as CCTL14-derived NPs, will participate in forming a pool of models for human cells that can be employed for basic and medical research, drug screening and cell therapy.

Clinical Trials

Despite discrepancies in guidelines, hESC-based treatments are entering clinical trials for diseases like Stargardt’s Macular Dystrophy and Dry Age Related Macular Degeneration.

Study Limitations

1
hESCs are prone to instability and variations, making their culture a challenging process.
2
Transplantation of neural precursors is coupled with the risk of tumor formation.
3
Large discrepancies in the guidelines between the NIH Stem Cell registry and the FDA’s requirements make the majority of hESC used not yet amenable to be tested in clinical trials.

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