Engineered human neurons rebuild damaged spinal cord circuits
Spinal cord injuries affect an estimated 15 to 20 million people worldwide, often causing lasting impairments in movement, sensation and independence. Such injuries can be especially devastating when they occur at the level of the neck, where damaged spinal circuits disrupt signals that control the diaphragm, the main muscle used for breathing.
Spinal cord injuries affect 15 to 20 million people globally, often causing lasting impairments in movement, sensation, and independence. High-level cervical injuries can disrupt critical neural circuits controlling breathing. Current therapies do not rebuild lost neurons and connections. Researchers at Gladstone Institutes have engineered human stem cell-derived spinal interneurons that can survive after transplantation in injured rats, connect with host neural circuits, and improve breathing-related motor function.
V2a interneurons, involved in movement control, are critical after spinal cord injury. Gladstone scientists developed methods to create transplantable human V2a interneurons, optimizing them for repairing injured spinal circuits. After one week of transplantation in adult rats, the new cells survived and formed connections with nearby spinal cord cells.
Two months later, these cells showed increased diaphragm activity when activated, and the rats maintained better breathing during low oxygen or high carbon dioxide challenges compared to untreated rats. The transplanted cells appear to provide additional respiratory capacity. Further research will focus on identifying optimal transplanted V2a interneuron subsets and testing the therapy in larger animals and later stages of spinal cord injury.
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