Major Points and Findings:
- Introduction to Stem Cells:
- Human embryonic stem cells (hESCs) are a valuable resource for studying human development and diseases. However, their use is limited due to ethical concerns related to their procurement.
- Recent advances have led to the creation of induced pluripotent stem cells (iPSCs) from skin fibroblasts, which don't involve the use of embryos. These cells can help in understanding molecular mechanisms underlying neuron dysfunction and death in various diseases. They also serve as a platform for drug development.
- Pluripotent Stem Cells:
- hESCs can transform into various cell types, including neural subtypes like dopaminergic neurons, motor neurons, and others.
- Ethical concerns arise from the fact that embryos are destroyed during the procurement of hESCs.
- A significant breakthrough was the discovery that fibroblasts (cells found in connective tissues) can be reverted to an embryonic stem cell state through reprogramming. These reprogrammed cells, termed iPSCs, have similar properties to hESCs but don't involve the use of embryos.
- Spinal Muscular Atrophy (SMA):
- SMA is a genetic disease that leads to the loss of motor neurons in the spinal cord and is a leading cause of infant mortality.
- The disease is caused by a mutation in the survival motor neuron (SMN) gene, resulting in a loss of SMN1 protein.
- Humans have two versions of SMN: SMN1 and SMN2. While SMN1 produces a full-length protein, SMN2 produces a truncated version due to a genetic mutation. The severity of SMA is influenced by the amount of full-length SMN protein produced by SMN2.
- SMA Model Systems:
- Various models, including mice, have been used to study SMA. However, mice models might not adequately represent the human condition due to physiological and anatomical differences.
- Fibroblasts from SMA patients have been studied extensively. These cells are easy to obtain and grow but don't naturally produce motor neurons or related cells.
- iPSCs derived from patients can be used to produce human cells with the genetic mutation, making them valuable for studying the disease.
- Findings from the Study:
- The researchers generated iPSCs from fibroblast samples taken from a three-year-old boy with Type I SMA and his unaffected mother. These iPSCs were shown to be pluripotent and retained the genetic characteristics of SMA.
- The iPSCs were able to produce neural cells with markers typical of motor neurons.
- While both affected and non-affected iPSCs initially produced similar numbers of motor neurons, over time, there was a reduction in the number and size of motor neurons derived from the affected iPSCs. This suggests that an intrinsic property of the SMA derived motor neuron leads to damaged or dying neurons.