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Stem Cell Consortium Uses Induced Adult Stem Cells to Study Complex Diseases

Stem Cell Consortium Uses Induced Adult Stem Cells to Study Complex Diseases

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  • The Stem Cell Consortium is studying polygenic diseases using induced pluripotent stem cells.
  • Induced pluripotent stem cells are adult stem cells which are re-programmed by scientists which have the capability to grow into any cell type of the body.
  • The effects of various genes in a polygenic disease are understood using these induced pluripotent stem cells.

The US National Heart, Lung, and Blood Institute's (NHLBI) Next Generation Genetic Association Studies Consortium conducted studies that utilized induced pluripotent stem (iPS) cells to study polygenetic diseases.


Stem Cell Consortium Uses Induced Adult Stem Cells to Study Complex Diseases

Stem cells have revolutionized medical research, with most of the research conducted using these stem cells being associated with diseases caused by a single gene mutation following a Mendelian pattern of inheritance. Examples of such monogenic disorders are muscular dystrophy, Huntington's disease and cystic fibrosis. However, genome wide association studies have shown that many of the diseases are multi-gene disorders where there are numerous genes that contribute to the progress of a single disease. The inheritance pattern of these diseases, which is influenced by the effects of multiple genes like in diabetes and hypertension, require a deeper understanding of the effect of these genes on the cellular level.

Induced Pluripotent Stem Cells

Dr. Shinya Yamanaka in 2006 developed a method by which adult cells could be converted into pluripotent stem cells or cells that have the capability to develop into any cell type present in the body. Dr. Yamanaka was awarded the Nobel Prize for this ground breaking discovery 6 years later.

Dr. Shinya identified a method by which adult cells could be reprogrammed to become induced pluripotent stem cells (iPS). Until then it was believed that only embryonic stem cells could be pluripotent.

Four genes were added to mice skin cells which started a process that led to the skin cells getting converted into induced pluripotent stem cells. Scientists have now devised a method by which fewer genes can be used to induce pluripotent adult cells.

Apart from The US National Heart, Lung, and Blood Institute, other research projects with similar goals are being conducted by
  • The HipSci Initiative (UK)
  • The EU project Stem BANCC.
Harvard Stem Cell Institute's Dr. Chad Cowan said that at the juncture where a mass scale up of the iPS cells to be generated for thousands of individuals had just begun, the NHLBI had the vision to use these cells as a next step in genome wide association studies to integrate the molecular mechanisms of certain genes within the iPS cells.

Induced Pluripotent Stem Cells in Polygenic Diseases

The major challenge faced by scientists in understanding the mechanism of action of polygenic diseases like cardiovascular disease, was the difficulty to ascertain the effect of individual genes. Animal studies also prove inconclusive as the influence of individual genes is too subtle to be identified. Moreover, the responses exhibited in animal studies might be different in studies with humans. The research team that performed the studies on polygenic diseases generated the iPS cell lines, which required
  • 4-6 months of labor
  • $20,000 for each iPS cell line
  • Cell samples which were obtained from thousands of people
While designing drugs for specific diseases, the targets for the drug are clearly identified. The use of gene based studies like genome wide association studies have resulted in identifying the genes that are involved in the development of the disease. Scientists have faced a challenge in determining how the genetic variants could instigate the development of disease. Induced pluripotent stem cells will aid in understanding the systematic process by which gene variations lead to the development of disease, allowing translation of the gene studies into drug targets.

Use of Induced Pluripotent Stem Cells for Insight into Cellular Function

When iPS cells are derived from patients with Rett syndrome, it was found that the neurons had
  • Lower number of synapses
  • Fewer dendritic spines
  • Smaller cell bodies
  • Defects in electrophysiological and calcium signaling when compared to control neurons
When these cells were treated with gentamicin, it was found to block ribosomes and increased the translation of the gene MeCP2, the gene that is implicated in Rett syndrome, ameliorating the disease symptoms. Thus induced pluripotent stem cells can be used to gain an insight into the molecular changes that occur due to gene mutations and can also be used to understand the effects of drugs at the molecular level.

Findings of the Study Using iPS

The study conducted by the consortium showed that
  • The cell lines that were needed to understand the mechanism of polygenic traits do not need hundreds of samples.
  • The studies showed that fewer stem cell lines were required to analyze abnormalities in liver metabolism.
  • Small changes that occurred in gene expression were found to be associated with significant changes in a cell.
  • The effect of the gene alterations that occur may become apparent even before the differentiation of the stem cells.
  • The studies that were carried out could be used to ascertain the fundamental building blocks that are involved in the development of polygenetic diseases.

Complement to the Genome Wide Association Studies

Induced pluripotent stem cells show potential in identifying the functional aspects of gene variations by being a complement to genome wide association studies. However, Ms. Deborah Sweet, Stem Cell Editor, said that the technique required standardization of protocol for use as an effective research tool. She further added that the potential of this technique is an exciting prospect.

The technique could soon be used for personalized medicine where these stem cells can be used to identify targeted therapeutics.

References :

Source: Medindia

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