Amniotic Fluid Stem Cells Treat Mice With Spinal Muscular Atrophy


A multi-center study that included labs from the United Kingdom, Italy and France has culminated in a publication that describes the invention of a novel strategy to regenerate muscle in laboratory animals using human amniotic fluid stem cells.

Amniotic fluid fills a sac that surrounds the developing baby known as the amnion.  The amnion forms after about 12 days after the onset of fertilization, and amniotic fluid cushions and protects the baby, helps maintain a steady temperature around the baby, helps the baby’s lungs grow and develop since the baby breathes in the fluid, helps the baby’s digestive system develop since the baby swallows the fluid, provides a medium through which the baby swims and moves and therefore helps the bones and muscle develop, and prevents the umbilical cord from being squeezed.  Amniotic fluid stem cells are sloughed from the amniotic membranes and other surfaces as well, and have the ability to develop into several different cell types, including skin cells, muscle cells, neurons, cardiac tissues, kidney, liver, cartilage, bone, tendon, and others.  These cells are potentially useful for a broad range of future uses and therapeutic applications.

Particular muscular diseases result from the progressive degeneration of skeletal muscles. Stem cell treatments that use a patient’s own stem cells are problematic in such cases because the patient’s own stem cells have the same abnormalities as the degenerating muscles. Therefore, such “autologous” treatments would only add more dying cells to the muscle. New stem cells that can form new muscle that will not degenerate is required to effectively treat these diseases.

To this end, one such muscular degenerative disease, spinal muscular atrophy is a name given to a group of inherited diseases that cause progressive muscle damage and weakness that gets worse over time and eventually leads to death. Spinal muscular atrophy (SMA) patients possess mutations in SMN1 gene. SMN stands for “survival of motor neurons,” which indicates what this gene does; it encodes a protein that is absolutely essential for the continued survival of motor neurons. Motor neurons are spinal nerve cells that extend long processes called “axons” to skeletal muscles. Activation of the motor neurons causes the skeletal muscle to contract. Without motor neuron activation, the muscle is unable to contract. When the motor neurons die, the muscle is paralyzed and is unable to move.

Humans have two copies of the SMN gene on chromosome 5. SMN1 is found at the tip of chromosome 5 and SMN2 is found towards the middle of chromosome 5. SMA2 is expressed at very low levels in motor neurons. People with SMA have received two mutant copies of SMA1, one from each parent. Approximately, 4 of every 100,000 people have SMA.

There are four  forms of SMA.  SMA type I (Werdnig-Hoffman disease), which is the most severe, SMA type 1 results from mutations in SMN1 that prevent the production of any functional SMN1 protein. Even though SMN2 is available, not enough SMN protein is produced to prevent the neurons from dying. Symptoms appear in the first months of life, and there is rapid motor neuron death. The body organs operate inefficiently and the respiratory system operates poorly,which leads to a high risk of pneumonia-induced respiratory failure. Babies diagnosed with SMA type I do not usually live past two years of age and death can occur as early as within weeks in the most severe cases

SMA type II or Dubowitz disease affects children. Children with SMA type II are never able to stand and walk. However, they can maintain a sitting position at some time in their life. Weaknesses manifests some time between 6 – 18 months. The progression of this disease varies greatly. Body muscles are weakened, and the respiratory system is a major concern. Life expectancy is somewhat reduced but most SMA II patients live well into adulthood. SMA type II patients have at least three copies of SMA2, since the copies of SMN1 cause reduced production of SMN1 protein to levels similar to those observed as SMN2.

SMA type III, which is the least severe, results from at least three copies of SMN2, and in rare cases, SMA type IV, patients have four copies of SMN2, since both copies of SMN1 have undergone mutations that reduce their levels of expression to those of SMN2. The symptoms of SMA type IV begin in adulthood, In almost all cases, there is a family history of SMA.

Mouse models of SMA have been particularly useful in the study of this disease, and Dr. Paolo de Coppi, who, which his colleagues at the UCL institute of Child Health showed that intravenous administration of human amniotic fluid stem cells could increase the strength of SMA animals and improve their survival. This study demonstrated the integration of amniotic stem cells into skeletal muscle.

According to Dr. Coppi, “SMA is a genetic disease affecting one in 6,000 births. It is currently incurable and in its most severe form children with the condition may not survive long into childhood. Children with a less severe form face the prospect of progressive muscle wasting, loss of mobility, and motor function. There is an urgent need for improved treatments. We now need to perform more in-depth studies with human AFS (amniotic fluid stem cells) in mouse models to see if it is viable to use cells derived from the amniotic fluid to treat diseases affecting skeletal muscle tissue.”

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).