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DRI Answers Stem Cell Question - Part 1

by Diabetes Research Institute on Thursday, July 28, 2011 at 9:45 am on T1 Diabetes Cure - Global Headquarters and Diabetes Research Institute Facebook pages.

This DRI Thursday we’re responding to a question posed by one of our Facebook friends.  The answer comes from DRI’s Director of Stem Cell Development for Translational Research Dr. Juan Dominguez-Bendala, who you’ve heard from previously.  A fun tidbit of info about him is that prior to joining the DRI faculty he worked at the Roslin Institute (Scotland, UK), known for the cloning of Dolly the sheep!

We’ll share one half of his answer today and the other half next week.

Question: “What sort of research, if any, is being done at the DRI with stem cells? I underwent Adipose stem cell treatment in February and I have had some remarkable results. I have also been a type 1 since 1972 being diagnosed at age 9. Any info would be much appreciated. “

Answer from Juan Dominguez-Bendala, Ph.D.:

At the DRI, we are pursuing several strategies to develop an unlimited cell supply. A major focus is the use of stem cells, including adipose derived cells.  Stem cells are “naïve” cells and proliferate at a remarkable rate, which makes them ideal candidates to alleviate the shortage of insulin-producing cells.

When given the required “instructions,” stem cells have the potential to become any cell type of the body including insulin-producing cells. Much of our research is focusing on doing just that – developing safe, efficient protocols to provide stem cells with the instructions they need to develop into insulin-producing cells and this work is made possible through the generosity of private donors.

Combining technical expertise in molecular and cell biology, immunology and tissue engineering, our team is working in the following areas to achieve this goal:

Improving Protocols
In order for a stem cell to become an insulin-producing cell, it must go through a series of developmental stages where "switches" are turned on, in a particular sequence, to signal the cell to develop along an intended path.

We have been using protein therapy to deliver these sequential signals, which is believed to be safer and more efficient than gene therapy. While we have successfully inserted these signals, the rate of efficiency has been limited. Only a small percentage of cells actually received the messages and were able to move toward the desired function.

We are now using a more effective approach by instructing the cells to make their own proteins. Molecules called "messenger RNAs" are being used to relay the developmental signals.

While this approach has been theoretically feasible for years, recently-discovered technologies make it practical.  Initial study results are promising.  By using messenger RNAs, more cells are receiving the developmental signals compared to previous approaches. We are now testing the order, timing and duration of the signals to achieve maximum efficiency.

Stem Cell Safety

A key factor that makes stem cells such an attractive option to overcome the shortage of insulin-producing cells is their ability to reproduce at a rapid rate.  However, this same ability can pose a potential threat.  If one cell remains “undifferentiated” and keeps dividing, it can result in the formation of tumors.  We are working to eliminate that risk by developing safer, more efficient protocols for the use of these cells.

To accomplish this, we are developing two "suicide genes" that will be incorporated into the differentiation protocol and activated only if a cell continues to divide or if it becomes something other than an insulin-producing cell.  Therefore, these suicide genes will selectively destroy only the cells that pose a threat of becoming tumors while those that do not divide will be spared. This chemical product can be either added to the cells in culture or given orally to the patient and when silent, will not affect the cell in any way.

Using specific regulatory elements, we can control, at will, the types of cells in which these suicide genes will become activated. In our experimental design, we will introduce two of these suicide genes into embryonic stem cells by means of a method termed electroporation. In short, an electric shock opens pores in the membrane of the cell, allowing the penetration of the genes. Once inside the cell, these genes will find their way to the nucleus and the genome of the host.

To be continued…next DRI Thursday!


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