A 3-D cell model derived from patient stem cells is able to imitate motor neurons from spine muscle atrophy (SMA) New research suggests that patients can become better physiological agents for the study of disease mechanisms and screen therapy candidates.
In the study "Cell cycle inhibitors protect motor neurons in muscle muscle atrophy organoleptic model,"Was published Cell death and disease.
In most cases, SMA causes genetic mutation SMN1 a gene that has led to a decrease in the survival rate of the motif neuron (SMN) protein.
Although this protein produces many body tissues, it remains to be fully understood why motor neurons are one of the most heavily affected types of cells.
Based on animal studies and the fact that the onset of SMA can occur in the first months of life, it is suggested that SMA also has neurodevelopmental disorders "if the mechanical neurons in the spinal cord are not properly formed and those who eventually survive could be rapidly post-partum degeneration" said the researchers. But this hypothesis is still controversial.
Leading researchers Singapore National University, the team asked these questions by developing a laboratory cell model that allowed them to study the development of people with SMA motor neurones and neurodegeneration.
This model, called spinal nerve organics, is an in vivo similar three-dimensional motor neuron model in the spinal cord derived from human-induced pluripotent stem cells (iPSCs). These cells are derived from skin or blood cells that are reprogrammed back in a stem cell-like state, allowing the development of an unlimited source of any kind of human cells that is needed.
Nervous organotypes are 3-D culture systems that give a new form to the processes and organization of the central nervous system and are "There is a huge potential for research on the development of human nervous," said researchers.
Scientists were able to obtain vertebrate organoids from healthy human cells and SMA donor cells. These organs contained many cells that were naturally present in the abdominal spinal cord – mechanical neurons, astrocytes, and internodes – indicating that the model was suitable for mimicking the natural in vivo back nerve environment.
Using these organs, scientists compared the development of healthy subjects with motor neurones with those who were from SMA patients. They found no change in the formation of neuron precursor cells or mature neurons, "studying SMA," emphasizing that the formation of motor neurons has not diminished. "
The neurons of the SMA motor die quickly after maturity, and most importantly, the higher the severity of the SMA of the patients (type 1 and type 2), the greater the severity of mechanical neuronal damage in the spinal organelles.
Researchers also more closely tested the death of motor neuronal cells and found that engine neurons from SMA patients anabancult re-activated cellular replication. If replication is blocked, the neurons of the SMA engine lived significantly longer in the treatment of vertebrate organoids with a small molecule inhibitor, known as the whole CDK inhibitor.
"It confirmed that neuronal organs are suitable for small molecule screening methods and can be considered as an additional screening phase before the transition in vivo models, "said researchers.
These 3-D models could also efficiently reproduce the spectrum of SMA expressions and use it to investigate how neurodegeneration occurs.