by Ellen Mintz
It's early Friday morning, and still dark and cold, the time of morning when only some animals are active and humans are all still sleeping. I have my gear loaded in the car, and am ready to get to work. I am not going out into the field to catch kangaroo rats, catch fish, or track rattlesnakes (although those all sound like fun projects!). My gear is a pen, notebook, and collection of research abstracts, and I am headed down to a meeting in the sunny beach town of La Jolla, CA, where some of the most innovative and cutting edge research in stem cell biology is taking place at research institutions like The Salk Institute, The Scripps Research Institute, and UC San Diego. The amazing applications of this research could improve the lives of many and result in hundreds of applications in science and medicine.
|The Salk Institute in La Jolla|
Stem Cell Basics
Stem cells are unique cells located in special places around the body that can differentiate into specialized cells or self renew and become more stem cells. They are influenced to change by their environment, which includes other cells and factors released by those cells and by the stem cells themselves. The ultimate stem cells of the body, eggs and sperm, are referred to as totipotent, meaning they can differentiate into any tissue type in the body. Pluripotent stem cells have the ability to differentiate into any of the three tissue types in the body: mesoderm, endoderm, or ectoderm. A neural progenitor cell is an example of a multipotent stem cell; it has the ability to differentiate into neurons or glial cells. Stem cells can also be unipotent, meaning they are the direct precursors to a specific cell type.
|Stem Cell Differentiation|
The gold standard of stem cells are human embryonic stem cells (ESCs), obtained from the inner cell mass of a four day old blastocyst (post fertilization ball of cells). These totipotent cells can be induced to become any tissue type, and are easily obtained from IVF clinics. However, some people have ethical concerns over their use. In 2006, a method was developed to reprogram mature adult cells back into a pluripotent state, similar to embryonic stem cells! This technique won Shinya Yamanaka and Sir John Gurdon the Nobel Prize in Science and Medicine this year, something that definitely has huge prospects for regenerative medicine, cell therapies, and studying how different diseases develop.
Stem cells are cultured, or grown, flat in dishes or allowed to form spheres, mimicking the environment that they are naturally found in the body and surrounded by growth and differentiation factors. These cells can then be used in cell therapies to treat many different diseases and conditions, a really exciting prospect for regenerative medicine! Let’s look at some of the diseases that have the potential to be treated or cured eventually using stem cells.
|Sir John Gurdon, 2012 Nobel Prize Winner|
|Shinya Yamanka, 2012 Nobel Prize Winner|
Parkinson’s disease is a neurodegenerative disorder caused by a loss of dopaminergic neurons (neurons that release dopamine as a neurotransmitter) in the brain, in an area called the substantia nigra. It is one of the most common nervous system disorders in the elderly, and exhibits symptoms such as muscle rigidity and tremors, stooped posture, movement problems, and issues with balance and walking.
|The brain affected by PD|
Takagi et al. (2005) used primate ESCs and differentiated them into progenitors of dopaminergic neurons, then treated them with factors that would allow them to remain differentiated. These neurons were then transplanted into cynomolgus monkeys that were treated with 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (Try saying that five times fast! We’ll just call it MPTP), which is used to induce PD in animal models. Following transplantation, these neurons were still functional in their dopaminergic activity by releasing dopamine, and were actually able to diminish PD symptoms in the monkeys!
Heart Attack and Cardiac Function
In 2012, a clinical trial called CADUCEUS (full name: CArdiosphere-Derived aUtologous stem Cells to reverse ventricular dysfunction) treated patients who had suffered a myocardial infarction, or heart attack, with stem cells and looked to see how it affected the damaged heart tissue.
|Naming clinical trials|
|Damaged heart tissue following myocardial infarction|
Type II Diabetes is a disease that is characterized by high blood glucose levels, usually resulting from a resistance to insulin or a lack of insulin production. Insulin is a hormone produced by special cells (the islet cells) in the pancreas that causes an uptake of glucose by tissues such fat, liver, and muscles. When cells do not respond to insulin, glucose from the meal you just consumed continues to circulate in your blood, leading to problems such as slowly healing infections, blurred vision, fatigue, pain and numbness in the extremities, and eventual eye, kidney, and cardiovascular disease. Family history and genetic factors play a role in the development of Type II Diabetes, and unhealthy lifestyle choices involving poor diet and lack of exercise only exacerbate the problem. The best cell therapy to treat Type II Diabetes is islet cell transplantation, however there is a high cost associated with this as well as probable negative immune reactions.
|Insulin producing islet cells in the pancreas|
Jiang et al (2011) transplanted placental MSCs into ten patients with Type II Diabetes who had insulin dysfunction and poorly controlled blood glucose levels, as well as coronary artery disease, kidney disease, atherosclerosis, and large limb neuropathy. The patients received the transplant and continued to inject insulin as well, however this was controlled for in the results by measuring the presence of c-peptide, a molecule cleaved from the insulin precursor proinsulin to make insulin. There were no obvious negative side effects to the transplantation, and C-peptide levels were significantly elevated, meaning the islets were working and creating insulin! The MSCs were able to differentiate and function as islet cells!
Current Challenges and Future Directions
|Cool fluorescent stem cell|
Keep an ear out for stem cells in the news, and an eye on these blogs for more stem cell biology from one of my CIRM Bridges program peers…
For more information…
The California Institute for Regenerative Medicine funds stem cell research involving hESCs in particular.
To see how stem cells are being studied at Cal Poly, check out the link for the CIRM Bridges MS Specialization in Stem Cell Research at Cal Poly!
Special thanks to the half of the CIRM Bridges program students in my car for all their feedback!
Jiang, R., Z. Han, G. Zhuo, X. Qu, et al. 2011. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Frontiers of Medicine 5(1): 94-100.
Makkar, R., R. Smith, K. Cheng, K. Malliaras, L. Thomson, et al. 2012. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomized phase 1 trial. The Lancet 379:895-904.
"Parkinson's Disease." PubMed Health. PubMed, 26 Sept 2011. Web. 15 Feb 2013. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001762/>.
Stem Cell Basics. In Stem Cell Information. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009 [cited Friday, February 15, 2013. http://stemcells.nih.gov/info/basics/Pages/Default.aspx
Takagi, Y., J. Takahashi, H. Saiki, A. Morizane, et al. 2005. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. The Journal of Clinical Investigation 115(1):102-109.
"The 2012 Nobel Prize in Physiology or Medicine - Press Release". Nobelprize.org. 15 Feb 2013 http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html
"Type II Diabetes." PubMed Health. PubMed, 28 June 2011. Web. 15 Feb 2013. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001356/