Direct Cellular Reprogramming Produces Pancreatic Beta Cells
Ann Carroll, PhD*

A key aim of regenerative medicine is to use adult cells from an individual to generate a different cell type that is missing in that individual, due to illness or injury. Recent success in the laboratory using induced pluripotent stem (iPS) cells -- taking adult cells and engineering them to become embryonic-like stem cells, a potential source to then generate other cell types – holds promise for this approach (1, See Briefing).

Now, a new study using mice provides evidence that this reprogramming approach may work at a simpler level, taking one type of adult cell, the pancreatic exocrine cell, and converting it directly to another type of pancreatic cell, the insulin-producing beta cell, which is characteristically missing in individuals with Type 1 diabetes.

This approach, direct cellular reprogramming, was taken by the Harvard research team led by Doug Melton (2). The researchers knew that these two types of pancreatic cells with different functions are derived from a common progenitor cell during embryonic development (3). They reasoned that, by using a method similar to that used to generate iPS cells, they could convert or reprogram pancreatic exocrine cells to beta cells.

The researchers delivered various combinations of factors important for development of pancreatic beta cells to pancreatic exocrine cells in young mice using viral vectors. The team found a combination of three specific factors which could convert exocrine cells to insulin-producing beta cells.

Also, the viral vectors used in this study, unlike those of initial iPS studies, do not become a permanent part of the target cell’s DNA, an important step forwards when considering safety for future clinical applications.

This study provides proof that direct cellular conversion of one adult cell type into another adult cell type is possible. In some tissues, it might be possible to bypass the multi-step process of reverting adult cells to an embryonic-like state and then directing them back to adult cells.

*Author Affiliation
Ann Carroll, PhD
Freelance Consultant

Notes 
1. Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.

2. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J., and Melton, D. A. (2008). In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455, 627-632

3. More on understanding progenitor cells: see Briefing.

Posted October 15, 2008