all of us do not have the opportunity to actively partake in research endeavors, we can still help in the fight. It is up to us to educate ourselves on these topics. Stem cells have been a point of heated contention for years now. However, the vast majority of the public group all stem cells into only one narrowly defined category. By educating those around us, we are able to break down the walls of stigma that have for so long blocked the eyes of the public to the truth.
At its very core, medicine is simply a means to help those who cannot help themselves. Stem cells are but another tool in the repertoire of modern medicine. However, their full utilization has not yet come to fruition. Stem cells hold the potential to meet the most intractable demands plaguing the human condition. The wealth of research focusing in on these cells is now occurring at an ever-rapid pace. In order for it to proceed to heights unknown, it will need a collective endorsement the world over.
Krishna S. Vyas
University of Kentucky College of Medicine
Rahul Annabathula
University of Kentucky
See Also: Adipose: Existing or Potential Regenerative Medicine Strategies; Alzheimer’s Disease; Blood Adult Stem Cell: Existing or Potential Regenerative Medicine Strategies; Cartilage, Tendons, and Ligaments: Existing or Potential Regenerative Medicine Strategies; Clinical Trials, Ethics of; Heart: Existing or Potential Regenerative Medicine Strategies; Heart Disease; Neural: Existing or Potential Regenerative Medicine Strategies; Parkinson’s Disease.
Further Readings
Koh, Y. G., et al. “Mesenchymal Stem Cell Injections Improve Symptoms of Knee Osteoarthritis.” Arthroscopy, v.29/4 (2013).
Lie, D. C., et al. “The Adult Substantia Nigra Contains Progenitor Cells With Neurogenic Potential.” Journal of Neuroscience, v.22 (2002).
Lumelsky, N., et al. “Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similar to Pancreatic Islets.” Science, v.292 (2001).
Makkar, R. R., et al. “Intracoronary Cardiosphere-Derived Cells for Heart Regeneration After Myocardial Infarction.” Lancet, v.379 (March 10, 2012).
Soria, B., et al. “Insulin-Secreting Cells From Embryonic Stem Cells Normalize Glycemia in Streptozotocin-Induced Diabetic Mice.” Diabetes, v.49 (2000).
Clinical Trials Outside the United States: Amyotrophic Lateral Sclerosis
Clinical Trials Outside the United States: Amyotrophic Lateral Sclerosis
287
289
Clinical Trials Outside the United States: Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a devastating neurodegenerative disorder characterized by rapidly progressive weakness due to degeneration of motor neurons in the brain cortex, brain stem, and spinal cord. Treatments for ALS have been limited due to the diverse nature and unknown etiology of the disease. Riluzole (Rilutek) is the only FDA-approved treatment known to improve survival in ALS patients, but only by a span of several months. Much of this difficulty in finding treatment relates to the various etiologies and heterogeneity that exist within ALS. In recent years, much interest has been divested into the use of human pluripotent stem cells for the treatment of ALS. While the initial idea was to use the pluripotent stem cells to replace lost motor neurons in ALS, this idea proved impractical given the long-distance projections and complicated functional connections that these new stem cell motor neurons would need to make in order to replace their predecessors.
Another more feasible option would be to use the pluripotent stem cells to re-create support cells in the neuronal environment, nourishing already existing motor neurons to thrive and possibly detoxifying the environment to prevent further cell death. Support cell types in the nervous system can be generated from other tissues such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs). Mesenchymal stem cells can be derived from existing connective tissue such as bone marrow, cartilage cells, and fat cells, as well as from umbilical cord tissue. Neural stem cells can be derived from the fetal brain. Preclinical studies have shown the ability to use MSCs and NSCs to generate functional support cells to improve motor neuron survival in ALS models. The hope is to determine the safety and efficacy of using mesenchymal and neural stem cell transplantation into patients with ALS and maximize the therapeutic benefit achievable with such treatment.
Most of the current clinical research using an MSC or NSC model for the treatment of ALS is done outside the United States, in countries like Italy, Iran, Israel, and Mexico. The majority of these countries focus on the use of MSC therapies for the treatment of ALS, most likely due to the fact that mesenchymal stem cells avoid the ethical and practical issues of embryonic and fetal-derived stem cells by being easily derived stem cells from adult connective tissues.
Italy
The first of such clinical trials utilizing MSC therapy to treat ALS was done by the Mazzini group at the San Giovanni Bosco Hospital in Torino, Italy, in 2003. Letizia Mazzini et al. isolated MSCs from allogeneic ALS patient bone marrow aspirates, and in their initial clinical study, seven ALS patients received transplantation with these MSCs into their thoracic spinal cord with varying numbers of injection sites and cell numbers. Patients were observed more than four years after their surgeries, and while there was no observed clinical or functional improvement in these patients, no serious side effects or detriment to neurological function was reported over the entire follow-up period. However, due to the small number of patients tested and inconsistency in the number of MSCs administered per patient, there was no definitive conclusion as to whether implantation of MSCs into ALS patients was undeniably safe and well tolerated.
To address these issues, Mazzini et al. performed a second Phase I clinical trial with a group of 19 ALS patients and observed these patients for up to 9 years after surgery using the same procedure and same cell line. Again, while no significant functional improvement or slowed progression of disease was observed in these groups, there were still no major side effects after receiving the transplantation, and the treatment was deemed to be overall safe and well tolerated with no immediate or long-term harmful consequences. The only international group to study neural stem cell transplantation in ALS patients is the Vescovi group in Terni, Italy. Their study aims to deliver human neural stem cells into the spinal cord of 18 ALS patients in a Phase I clinical trial (NCT01640067). The study is currently ongoing with no results published.
Israel
BrainStorm Cellular Therapeutics in recent years developed human bone marrow stromal-derived MSCs that are differentiated into specialized neuron-supporting cells to secrete neurotrophic factors, named MSC-NTF and trademarked as NurOwnTM. These cells are known to express the markers of neural support cells such as glial fibrillary acidic protein (GFAP) and glutamine synthase, as well as to secrete neurotrophic factors such as brain-derived neurotrophic factor (BDNF), glial cell line–derived neurotrophic factor (GDNF), and insulin-like growth factor-1.
Hadassah Medical Organizations in Israel in 2010 collaborated with BrainStorm Therapeutics to start a Phase I/II open-safety clinical trial using the intrathecal and intravenous administration of NurOwn cells into patients with ALS. The study ultimately showed that the intravenous and intrathecal injection of these cells was safe via lumbar
