Transplanted human neurons joined the respiratory network in rats with spinal cord injuries

Transplanted human neurons joined the respiratory network in rats with spinal cord injuries

On August 5, the Gladstone group published a study in Science Translational Medicine. After transplantation, human V2a interneurons received signals from the rats’ neural network, relayed them onward, and helped the animals cope with increased respiratory demand.

A cervical spinal cord injury can disrupt the pathway from the brainstem to the diaphragm, the muscle that inflates the lungs. Anna Zholudeva’s team tested whether a specific type of interneuron could bridge this damaged circuit.

The researchers generated V2a interneurons from reprogrammed human cells capable of developing into different cell types. One week after the injury, they injected these neurons into the cervical spinal cord of adult rats. Two months later, the transplanted cells had formed neural connections with the rats’ neurons.

The team tested the new connection in both directions. When the researchers used light to activate the transplant site, diaphragm activity increased. When they activated the rats’ own respiratory neurons in the brainstem, the transplanted cells responded. The transplant received signals from the rats’ neural network and relayed them onward to the diaphragm.

The rats were then given air with either a low oxygen concentration or excess carbon dioxide. Under these conditions, the diaphragm must work harder. According to a Gladstone press release, three quarters of the animals with V2a transplants completed the tests without difficulty, while most injured rats that did not receive a transplant showed signs of respiratory failure. In this model, the researchers measured the effect both within the neural circuit and in a respiratory challenge test.

A 2023 experiment in mice showed that recovery of walking depended on regenerating axons from specific neurons reconnecting with their natural targets. In the current study, the researchers traced the full sequence for a cell transplant: whether it received a command, whether it relayed that command onward, and whether respiratory function changed under increased demand. This gives the transplant a specific role: bridging a defined break in neural connectivity.