Methods of Generating Induced Pluripotent Stem Cells

There are a few primary methods used for generating iPS cells. The most common approach involves introducing genes that code for transcription factors associated with maintaining pluripotency. The four factors originally used were Oct4, Sox2, Klf4, and c-Myc. These factors are often delivered into the fibroblasts using retroviruses or lentiviruses. Viruses integrate their DNA into the host cell genome which allows for sustained expression of pluripotency genes. More recently, non-integrating methods have been developed using episomal vectors, Sendai virus, proteins, mRNAs, and small molecules to reduce genetic modification. This helps avoid potential tumor formation from insertional mutagenesis.

Properties and Potency of Induced Pluripotent Stem Cells

Once generated, Global Induced Pluripotent Stem Cells demonstrate key features that are almost identical to embryonic stem cells. They have the ability to self-renew indefinitely in their pluripotent state and differentiate into various cell types of the three primary germ layers - endoderm, mesoderm, and ectoderm. This multipotency means iPS cells can differentiate into over 200 cell types like neurons, heart, pancreatic, and liver cells. Studies have also shown that mouse and human iPS cells form teratomas containing these three germ layers when transplanted into mice, demonstrating their developmental potential and clinical applicability.

Applications and Advantages of iPS Cell Technology

Due to their ability to generate any cell type in the human body, iPS cells offer tremendous promise for novel regenerative therapies. Some key applications include:

1. Disease modeling - Generating iPS cells from patients enables the study of diseases in a dish. This helps uncover disease mechanisms and potential drug therapies.

2. Drug discovery and toxicology testing - iPS cell-derived cells can be used as more accurate human models for high-throughput screening of new drugs and toxicological assessment without animal testing.

3. Tissue engineering and transplantation medicine - Differentiated cells derived from a patient's own iPS cells could be transplanted to replace damaged cells/tissues without immunosuppression. This represents a major advance for conditions like Parkinson's disease, diabetes, heart disease, and retinal degeneration.

4. Personalized medicine - A patient's individual iPS cells could help develop customized treatments based on their specific genetic background and disease state.

5. Avoiding ethical issues - Since induced pluripotent stem cells can be generated without embryonic stem cells, they avoid the ethical controversies surrounding human embryo research.

Global Advances in iPS Cell Research

Since the initial discovery, iPS cell research has advanced significantly around the world. Here are some key highlights:

- Japan has emerged as a global leader, with large investments from government and industry. Foundational studies on generating safe clinical-grade iPS cells were done here.

- Researchers in the UK and other European countries are studying disease modeling and screening applications. Clinical trials are underway for macular degeneration using iPSC-derived retinal pigment epithelial cells.

- In the US, the FDA approved the first clinical trial using induced pluripotent stem cells to treat vision loss in 2014. Advances continue across East Coast institutions like MIT, Harvard, and Johns Hopkins.

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