Stem Cell Research has Unlocked a Potential Cure to Type 1 Diabetes

Science is a beautiful process, a quasi-passing-of-the-intellectual-torch from researcher to researcher, often decades apart, ultimately yielding new translational medicine for a provider's repertoire.  

In the 1920s, diabetes mellitus was a real, pathologic beast and the development of a recombinant DNA protocol to produce synthetic insulin occurred in1978, but did not yield a cure to the disease.  In 2012, Schulz et. al fine-tuned a promising protocol in differentiating human embryonic stem cells (hESC) into glucose-stimulated, insulin-secreting tissue, having the potential for transplantation into Type-1 diabetic patients (2012). A stem cell researcher named Doug Melton has modified and expanded on Schulz's et. al work and has found a way to coax hESC into becoming functional beta cells. 

             

Figure 1 Figure 1a shows the extraction and grow processes of hESC (ES).
Figure 1b illustrates the various protein factors needed to differentiate hESC
(ES) to the subsequent pancreatic endodermal precursor cells (PE).

After 17 years of collaboration, researchers have defined a controlled differentiation process.  hESC are extracted from the inner cell mass of a blastula and implanted on top of a layer of treated embryonic skin cells.  The cells adhere to this layer, divide, and spread over the entirety of the dish producing a pluripotent embryonic cell line (NIH Stem Cell Information, 2014). Melton then subjected these embryonic stem cells to rounds of various transcription and growth factors, which activated differentiation genes that served to demarcate these cells into pancreatic endodermal precursor cells (PE) and later functional beta cells (Schulz et. al, 2014 and Pagliuca, F et. al, 2014). 

The potential for hESCs is undeniable. Significant bioethical debate surrounds the use of hESC in medicine which has postponed the development of this cure.  Many people object to the use of hESC because they are derived from the embryoblast cells of a blastula that may be inculcated with the same rights and dignities of a fully developed fetus (Stein, 2014).  As the future generation of providers, we will have to traverse this morally ambiguous area and decide if stem cell technology is ethically sound.  When do you think life starts?  I would argue that life is defined as any degree of higher cognitive development.

Because Type-1 Diabetes is characterized by autoimmunity of beta cells, Melton made Schulz's work viable by developing a strategy to evade the patient's immune system.  After implantation, the cells are provided a tea-bag-like shield in which they are not degraded, but still activated by intracellular glucose levels, producing insulin that can still diffuse out of the membrane like tea. Now we can push this to clinical trials.

Brilliant!

Figure 2 Figure 2 depicts Beta-like Cells (green) that produce insulin
that form islet clusters reminiscent of the beta islets of the pancreas

 Watch Melton Grow Beta Islet Clusters!


References:

NIH Stem Cell Information. 2014. Stem Cell Basics. NIH Online. [Internet]. Available from: http://stemcells.nih.gov/info/basics/pages/basics5.aspx

Pagliuca, F. Millman, J., Gurtlet, M., Segal, M., Dervort, A., Ryu, J., Peterson, Q., Greiner, D., Melton, D.. 2014. Generation of Functional Human Pancreatic B Cells In Vitro. Cell. [Internet]. Available from: http://hsci.harvard.edu/files/hsci/files/pagliuca_et_al_cell_2014.pdf

Schulz, T., Young, H., Agulnick, A., Babin, J., Baetge, E., Bang, A., Bhoumik, A., Cepa, I., Cesario, R., Haakmeester, C., Kadoya, J., Kell, J., Kerr, J., Robins, A.. 2012. A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells. PLOS One. [Internet]. Available from: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037004#pone.0037004-DAmour1

Stein, R. 09, October, 2014. Scientists Coax Human Embryonic Stem Cells into Making Insulin. NPR Online. [Internet]. Available from: http://www.npr.org/blogs/health/2014/10/09/354708628/scientists-coax-human-embryonic-stem-cells-into-making-insulin