Spinal cord tissue engineering using human primary neural progenitor cells and astrocytes

Bioeng Transl Med, 2023 · DOI: 10.1002/btm2.10448 · Published: March 1, 2023

Spinal Cord Injury Regenerative Medicine Biomedical

Simple Explanation

This study explores a new way to repair spinal cord injuries by creating a special tissue. This tissue is made from human spinal cord cells, including neural progenitor cells and astrocytes, grown on a supportive structure. The engineered tissue, called hscNT, helps the cells survive and mature, forming a structure similar to the spinal cord. When this tissue is placed into rats with spinal cord injuries, it reduces inflammation and promotes the growth of new nerve cells and blood vessels. Ultimately, this approach improved the rats' ability to move, suggesting it could be a potential treatment for spinal cord injuries in humans. The hscNT promoted neural circuit reconstruction and motor functional recovery.

Study Duration

2 Months

Participants

50 Female Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
Human spinal cord astrocytes (hscAS) promote the adhesion, survival, and neurite outgrowth of human spinal cord neural progenitor cells (hscNPCs) on a linearly ordered collagen scaffold (LOCS).
2
The hscNT inhibits inflammation and glial scar formation after transplantation into rats with SCI, creating a favorable microenvironment for neural and vascular regeneration.
3
Transplantation of the hscNT resulted in significant improvement of hindlimb locomotor function in rats with SCI, suggesting potential for neural circuit reconstruction.

Research Summary

This study introduces a novel centimeter-scale human spinal cord neural tissue (hscNT) construct composed of human spinal cord neural progenitor cells (hscNPCs) and human spinal cord astrocytes (hscAS) on a linearly ordered collagen scaffold (LOCS). The hscAS promoted hscNPC adhesion, survival and neurite outgrowth on the LOCS, forming a linearly ordered spinal cord-like structure with mature neurons and glia. Individual cells in the hscNT exhibited spontaneous calcium surges. Transplantation of the hscNT into rats with SCI created a favorable microenvironment, inhibited inflammation and glial scar formation, promoted neural and vascular regeneration, and notably, enhanced neural circuit reconstruction and motor functional recovery.

Practical Implications

Therapeutic Potential

Engineered human spinal cord implants containing astrocytes and neurons assembled on axon guidance scaffolds may have therapeutic potential for SCI.

Microenvironment Matters

Creating a favorable microenvironment with hscNT is crucial for endogenous neural regeneration and structural integration with host neural elements.

Cellular Crosstalk

The interaction between hscNPCs and hscAS is critical for SCI repair, suggesting that preconstructing a spinal cord-like tissue with a linear structure may be a promising strategy to enhance therapeutic outcome for SCI.

Study Limitations

1
The regeneration of neurites of neurons in the hscNT were limited in vivo compared with in vitro culture.
2
The site of SCI in vivo contains large amounts of myelin-associated proteins, which have been reported to inhibit axon extension by activating endogenous signaling pathways.
3
Inflammation and reactive oxygen species might also contribute to the adverse microenvironment at the injury site.

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