New Hope for Multiple Sclerosis (MS) with Epidermal (Skin) Stem Cells

http://www.em.mpg.de/index.php?id=230&no_cache=1

Multiple Sclerosis treatment with stem cells derived from the epidermis (skin)

To follow-up on medical breakthroughs via stem cell treatment from the previous post, Stanford University researchers have created cells from ordinary skin cells that could “rewrap” and protect nerve cells damaged in multiple sclerosis (MS), spinal cord injuries and other conditions.  The popular article was posted today, April 15th in the San Francisco Business Times.  The scientific research article can be found in the journal Nature Biotechnology.

This is monumental for those that are sufferers or have loved ones that suffer from MS.  I am an “empath” since my father suffered from a primary progressive form of MS.  Up until recently, the only available cutting edge techniques involved a combination of chemotherapy (see the many effects of chemo here:  effects of chemo) in junction with MS pharmaceuticals.  This was not an agreeable option for my father since MS left him with subpartial functionality of his limbs.   The magnitude of muscular functionality loss is dependent on the progression of the disease state in each individual.

The published research is ground-breaking for several reasons.  It will allow patients to use their own skin stem cells  to treat the demyelinated oligodendrocytes (see explanation below).  The treatment by one’s own skin stem cells will by-pass the need for immunosuppression and this research could produce cell therapy in as little as three weeks.  Dr. Marius Wernig, offers encouraging words when asked about the abundant amount of research focused on myelin:  “I think that these myelinating cells — or oligodendrocyte precursor cells, or OPCs — have a high chance of working after transplantation.”

Figure: Confocal visualization of central protein in myelin (PLP) in cultivated oligodendrocytes with an EGFP-tag (in yello-green) and an intracellular marker (in red).
Figure: Confocal visualization of central protein in myelin in cultivated oligodendrocytes with an EGFP-tag (in yello-green) and an intracellular marker (in red).

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation (rapid increase in numbers), migration, differentiation, and myelination to finally produce the insulating sheath of axons.  This insulating sheath (myelin) is important for the rapid conduction of electrical nerve impulses, which allows the neural signals to be efficiently sent and received.

Demyelinating disease is any condition that results in damage to the protective covering (myelin sheath) that surrounds nerve fibers in your brain and spinal cord. When the myelin sheath is damaged, nerve impulses slow or even stop, causing neurological problems.  As you can guess, the effects of this are devastating.

References: 

Bradl, M. & Lassmann, H. 2009. Oligodendrocytes: biology and pathology. Acta Neuropathol. 2010 January; 119(1): 37-53  Published online 2009 October 22. doi:  10.1007/s00401-009-0601-5

The Biotech Frontier in Texas; Birdbrains & Adult Stem Cell Therapy

Over a decade ago the polarizing topic of stem cell therapy came to the forefront of the media and stirred the sociopolitical undercurrents of the country.  The policies in question involved the use of embryonic stem cells for the purpose of research and eventually medical treatment of some of the most arduous diseases.

Fast-forward to 2013, currently the debate regarding the usage of  stem cells has been somewhat diffused by increased usage of autologous (cells or tissues obtained from the same individual) adult stem cells.  The usage of adult stem cells is less controversial because it does not require the destruction of an embryo.  The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found.  Adult stem cell treatments have been successfully used for more than 50 years to treat leukemia and related bone/blood cancers through bone marrow transplants.  (See timeline below for the history of stem cells)

New Legislation in Texas

Figure 1 - photo illustration by: Todd Wiseman
Figure 1 – photo illustration by: Todd Wiseman

In April 2012, the Texas Medical Board passed new rules regarding the use of adult stem cell therapy. The new rules allow doctors to bypass FDA approval after they meet specific requirements set forth by the Texas Medical Board, which is also responsible for the licensing and disciplining of doctors.

How will the new rules affect you and me?  The new rules allow doctors to perform stem cell procedures as long as they are done for research and receive approval from an institutional review board selected by the governor of Texas.  The rules also require that patients sign informed consent forms.

Texas Gov. Rick Perry has been a long-time advocate for passing new legislation.  Perry has reported relief from very painful back problems after receiving injections of his own stem cells isolated from adipose (fat) tissue. Before treatment he found it difficult to walk up and down the stairs, but after two separate treatments (one was an injection of his own adult stem cells during surgery to fuse vertebrae in the governor’s spine, and the other was intravenously) he was able to run up and down the stairs.

This post will not try to address the multifaceted layers of government policy on treatment with stem cells, although they are very important and play an emotional part in the lives of many faced with pain and degeneration, but I hope to lay a foundation to understand the nature of adult stem cells and how they can be used for medical breakthroughs.

Need to Know Basics of Adult Stem Cells

Stem cells are the foundation for every organ, tissue and cell in the human body.  Stem cells may be able to repair or replace damaged tissue, thereby reversing diseases and injuries such as cancer, diabetes, cardiovascular disease and blood diseases, just to name a few.  Adult Stem Cells are non-embryonic cells that by definition, are unspecialized or undifferentiated cells that not only retain their ability to divide mitotically while still maintaining their undifferentiated state but also, given the right conditions, have the ability to differentiate into different types of cells including cells of different germ-origin – an ability referred to as transdifferentiation or plasticity (the quality of being easily shaped or molded).

Figure 2 - Known sources for Adult Stem Cells Image via docstoc.com
Figure 2 – Known sources for Adult Stem Cells
Image via docstoc.com

Birdsong and Hope for the Future 

We don’t commonly think about how amazing the logistics are in the development of birdsong, but one Argentinean man with a life-long passion for the study of birdsong revolutionized the understanding of stem cells and neurogenesis (the ability to produce new viable nervous tissue).

Canary

Fernando Nottebohm has long been fascinated with the similarities between human vocalizations and birdsong and in the 1960’s he began conducting research that revealed that male canaries experienced new neuronal growth in the song nuclei region of the brain prior to mating periods.  Surprisingly enough these findings were staunchly rejected, since the implication of similar neurogenesis in humans usurped long held beliefs about the brain’s inability to regenerate cells.

Nottebohm used a radio-actively labeled marker (thymidine) to show new neuronal cell growth.  Thymidine is an enzyme that has a key function in new DNA synthesis and cell division.   After injection, any new cells produced in the birdbrains would express radioactivity. Nottebohm and his team discovered large numbers of radioactive cells, many of which were nerve cells – new nerve cells were being made at an astonishing rate. The team wondered, could this regeneration be directed to heal damaged brain tissue?

Finally in 1998, inspired by Nottebohm’s work, Fred Gage and his team (using a technique very similar to Nottebohm’s radio-active marker) at the Salk Institute found that adult human brains were also able to make new nerve cells.

The Field of Stem Cell Research was Opened Wide

Suddenly, scientists could see the potential for using newly dividing brain cells to treat neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, Stroke, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, etc. If these stem cells could be delivered to the damaged part of the brain, maybe they would divide and specialize, replenishing the damaged tissue and restoring people to good health.

Figure 1 - A cluster of neural cells derived from stem cells in the lab of UW-Madison stem cell researcher and neuro-developmental biologist Su-Chun Zhang. The motor neurons are shown in red; neural fibers appear green and the blue specks indicate DNA in cell nuclei.
Figure 3 – A cluster of neural cells derived from stem cells in the lab of UW-Madison stem cell researcher and neuro-developmental biologist Su-Chun Zhang. The motor neurons are shown in red; neural fibers appear green and the blue specks indicate DNA in cell nuclei.

The History of Stem Cell Research 

1956 First successful bone marrow transplant between a related donor and recipient is performed by Dr E. Donnall Thomas in New York. The patient, who has leukemia, is given radiotherapy and then treated with healthy bone marrow from an identical twin.
1960 Researchers discover bone marrow contains at least two kinds of stem cells — blood or hematopoietic stem cells that form all the types of blood cells in the body and stromal stem cells that form bone, cartilage, fat, and connective tissue.
1960 First research report to indicate that the brain may generate new nerve cells is published, but not widely accepted.
Studies done by Fernando Nottebohm on birdbrain and song nuclei led to discovery of neural stem cells.
1968 British scientist Robert Edwards and his student, Barry Bavister, became the first to fertilize a human egg in the test tube. This is the beginning of in vitro fertilisation (IVF) technologies.
1968 First bone marrow transplant for non-cancer treatment. Dr Robert Good uses a bone marrow transplant to treat an eight year old boy with severe combined immunodeficiency syndrome (SCID). The donor is an HLA-matched sister.
1973 First bone marrow transplant between unrelated patients. A five-year old patient in New York with SCID is treated with multiple infusions of bone marrow from a donor in Denmark.
1978 The first IVF baby is born in England.
1978 Blood stem cells are discovered in human umbilical cord blood.
1981 Mouse embryonic stem cells are derived for the first time from the inner cell mass of a mouse blastocyst and grown in vitro.
1984-1998 Pluripotent stem cells are isolated. When exposed to retinoic acid, these cells differentiate into neuron-like cells and other cell types.
1989 Preimplantation genetic diagnosis (PGD) is developed — a method where a single stem cell can be removed from an IVF embryo and tested for inherited diseases.
1990 Bone marrow donor program initiated.
1990 Dr Thomas receives the Nobel Prize in Physiology or Medicine for his pioneering work on bone marrow transplants.
1995 Scientists at the University of Wisconsin derive the first embryonic stem cells from non-human primates.
1998
Timeline for stem cell research

Stem cells from IVF

Scientists at the University of Wisconsin, led by James Thompson, isolate and grow the first stem cells from human embryos. The embryos used in these studies were created by IVF.

1999 Researchers discover that stem cells can be made to differentiate into different cell types.
2001 President George W. Bush permits federal funding of embryonic stem cell research, but only on the 64 existing stem cell lines.
2004 Researchers in South Korea claim to be the first to clone a human embryo and then harvest the stem cells for research. The research is later found to have been fabricated.
2004 California becomes the first state in the USA to provide its own fund for embryonic stem cell research.
2005 George W. Bush’s restrictions on embryonic stem cell research are loosened.

References:

Filip S, Mokrý J, Hruška I (2003) Adult stem cells and their importance in cell therapy. Folia Biol.(Prague) 49: 9-14.

http://www.biotechlearn.org.nz/themes/biotech_therapies/timeline_for_stem_cell_research

http://www.inquisitr.com/219258/stem-cells-treatment-law-in-texas-will-allow-doctors-to-offer-experimental-treatments/

http://www.ipscell.com/2012/04/the-real-but-oft-ignored-dangers-of-adult-stem-cell-treatments/

http://www.nature.com/news/stem-cells-in-texas-cowboy-culture-1.12404

http://news.bbc.co.uk/2/hi/science/nature/4544777.stm

http://www.nytimes.com/2012/04/14/us/new-rules-on-adult-stem-cells-approved-in-texas.html?_r=0

http://www.tellmeaboutstemcells.org/stem-cell-basics/the-difference.php

http://www.texastribune.org/2012/04/13/medical-board-adopts-controversial-stem-cell-rules/

Birdbrain Breathrough. In Smithonian: Science and Nature [World Wide Web].  Kiester, Edwin Jr., and Kiester, William Smithsonian magazine, June 2002 [cited Sunday, April 14, 2013] Available at http://www.smithsonianmag.com/science-nature/birdbrain.html?c=y&page=2

What are adult stem cells?. In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2012 [cited Wednesday, April 10, 2013] Available at <http://stemcells.nih.gov/info/basics/pages/basics4.aspx>

2 Men in China Die of Lesser-Known Strain of Bird Flu

https://www.osc.edu/press/researchers-take-virus-tracking-software-worldwide

2 Men in China Die of Lesser-Known Strain of Bird Flu

The H7N9 Strain of Avian Influenza Virus (AIV) is Rare but Deadly

The three reported cases of H7N9 AIV are not linked and no other close contacts, such as family members have shown any symptoms as of March 31, 2013 but doctors are carefully monitoring the family.  Currently there does not appear to be any threat to the community.

Clinical Presentation of H7N9 and Treatment

All three cases of documented H7N9 began with fever, cough, respiratory tract infection, and pneumonia during the early stages of the illness. Five to ten days after the illness beganvere pneumonia with difficulty breathing, and some progressed into respiratory distress and two of the three died.

Treatment for H7N9 is limited to anti-influenza virus drugs; however, further research is needed to determine if this is the most effective treatment option.

The Avian Influenza Virus Becomes a Powerful Pathogen When Crossing the Species Barrier

Influenza A virus originates in ducks and expresses relatively mild symptoms in its ecological niche.  However, when the virus mutates and crosses species barriers it becomes a powerful pathogen.  Other bird species and mammals are more severely affected with symptoms ranging from very mild to very severe and ultimately death.  Figure 1 below shows how the virus can cross species barriers and mutate into different pathogenic strains.

Figure 1 - Influenza A Virus - Dabbling Duck - Illustration of the host range of influenza A virus with the natural reservoir of influenza A virus, accidental hosts, and the subtypes that have been identified in the different groups. Illustration by Rebecca Rönnmark and Eric Gisaeus.
Figure 1 – Influenza A Virus – Dabbling Duck – Illustration of the host range of influenza A virus with the natural reservoir of influenza A virus, accidental hosts, and the subtypes that have been identified in the different groups. Illustration by Rebecca Rönnmark and Eric Gisaeus.

Bioinformatics Provides Us With Tools to Trace The Avian Influenza Family Tree (Phylogenetics)

Phylogenetic analysis can be used to trace viral infection through a human population, and the Comparative Method uses phylogenies to trace the evolution of a specific genetic sequence or trait across different species.  Phylogentics is defined as the study of evolutionary relatedness among various groups of organisms through molecular sequencing data and morphological data matrices. Sequencing of DNA, RNA, and proteins provides us with genomic information that can be stored and used in computer analysis programs.  These programs employ algorithms to predict mutations and construct cladistics or phylogenetic (evolutionary) trees.

http://www.pnas.org/content/102/51/18590/F3.expansion.html
Figure 2 – Example of Phylogenetic Analysis of the viral polymerase that mediates adaptation of an avian influenza virus to a mammalian host

Copyright © 2005, The National Academy of Sciences

Cladistics and the Spread of the Avian Influenza

Cladistics refers to the scientific classification of living organisms, based on common ancestry, into evolutionary trees. Evolutionary trees are used by many researchers studying infectious diseases to understand the geographic and host origins of pathogens and how the pathogens change over time. Supramap puts phylogenies in a geographic context as well.

https://www.osc.edu/press/researchers-take-virus-tracking-software-worldwide
Figure 3 – Cladistics – AIV (H7) in 2012 – Screenshot of the spread of H7 influenza as produced by SUPRAMAP and visualized by Google Earth™. This view illustrates the historical spread of high pathogenic lineages (high-altitude red lines) and the recent local evolution of high pathogenicity (low-altitude red lines). [credit: Janies/OSU]
Resources:

Chinese Center for Disease Control and PreventionQuestions and answers about human infection with H7N9 avian influenza. (2013). Accessed April 1, 2013.

Decoded Science. Bird Flu H7N9: First Human Deaths in China. (2013). Accessed April 1, 2013

Infection Ecology and Epidemiology 2011. © 2011 John Wahlgren. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ohio Super Computer Center. Researchers take virus tracking software worldwide. (2012). Accessed April 1, 2013

New York Times. 2 Men in China die of lesser-known strain of bird flu. (2013). Accessed April 1, 2013.

Gabriel G, Dauber B, Wolf T; et al. (2005) The viral polymerase that mediates adaptation of an avian influenza virus to a mammalian host. Proceedings of the National Academy of Sciences of the United States of America 102 (51 18590-18595) doi:10.1073/pnas.0507415102

World Health OrganizationAvian Influenza Fact Sheet. (2011). Accessed April 1, 2013.