Research on Stem Cells

• What are stem cells?
• Sources of stem cells
• Types of stem cells
• Names of stem cells
  
• What does pluripotent mean?
• What does plasticity mean?
• What are the politics of stem cells?
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• 17. Are there more primitive types of stem cells hidden among blood stem cells, awaiting discovery?
• 19. Can cord blood stem cells repair damage to the Central Nervous System?
• 20. Can cord blood stem cells correct inherited metabolic disorders?
• 21. Can cord blood stem cells be used for organ regeneration?

To look up additional research articles, we recommend:

• PubMed - National Library of Medicine search engine,                         returns abstracts only
• Google Scholar - Google search of scholarly literature,                       sometimes returns entire article
  

Stem cells are defined as cells which meet 3 criteria:

1. They keep renewing themselves by dividing to make more stem cells.
2. Stem cells are not specialized: they don't have a specific task in the body.
3. Under the right conditions, stem cells will differentiate:  They will divide to make one stem cell plus one cell which is more specialized.  In this manner an initial collection of stem cells can evolve into many different types of specialized cells.

The US National Institute of Health (NIH) has an excellent website devoted to explaining Stem Cell Information.

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Anybody who follows news reports knows that stem cells have been found in many parts of the human body, including discarded baby teeth.  However, the concentration of stem cells in most body parts is a few cells per milliliter.  There are only 3 sources of stem cells which are used for stem cell transplants: 

1. bone marrow
2. peripheral blood (circulating in the body)
3. umbilical cord blood

For example, in cord blood the concentration of nucleated cells is millions per milliliter.  It has been said that "adipose tissue", or fat, is also a fairly rich source of stem cells, but not everybody is a candidate for harvesting stem cells from fat (although jokes many jokes can be made about the prevalence of obesity in the US).

If you try to read research articles about stem cells, you will need to know some basic nomenclature:

Embryonic stem cells are found in newly fertilized eggs, they are the foundation for building life.  They have the ability to divide almost endlessly to make more embryonic cells, which is called proliferation.

Once an embryo is a few days old, it has formed a ball of cells called a blastocyst, and the layers of this ball start to differentiate into more specialized types of stem cells.  There are 3 germ layers in the blastocyst which give rise to these 3 more specialized stem cell branches:

1. ectoderm - gives rise to the central nervous system, neurons
2. endoderm - gives rise to the lungs, gastrointestinal tract
3. mesoderm - gives rise to muscles, bone, and blood

This website is devoted to parent education about cord blood, and therefore the research sections are strictly about studies using stem cells from cord blood.  However, to talk about stem cells without mentioning politics is like avoiding the elephant in the middle of the room.

Many people object to research on embryonic stem cells.  Those people are eager to believe that research with cord blood stem cells are a viable alternative.  The people who make money from banking cord blood are also eager to believe that stem cells from cord blood can do anything.  These two groups acting together, either intentionally or by accident, have formed somewhat of an alliance to aggressively promote claims that cord blood stem cells are "pluripotent" and all research funding should go to cord blood stem cells.

Answer: Almost certainly. Examples:

Press Release 1 Nov 2000 from StemCells, Inc. (Nasdaq: STEM) "First Identification of Purified Blood Stem Cells as a Source of Mature Liver Cells; Published in Nature Medicine

Nature 20 June 2002 vol.417. Catherine Verfaillie of the U. Minnesota Medical School and her team claim to have extracted "multipotent adult progenitor cells" from adult bone marrow which can turn into every type of tissue in the body, just like embryonic stem cells.

Press release 19 July 2004 from Viacell and NETCORD announces the first demonstration that neonatal "unrestricted somatic stem cells" (USSCs) can be robustly expanded in vitro (in the lab) to very large numbers and can differentiate, in vivo (in living humans), into a number of tissue types and take on the properties and specific functions of the cells in those tissues: blood, bone, cartilage, heart, liver, and nerve cells.

Reference:

• "A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential"; published in the peer-reviewed article by Kogler et al., Journal of Experimental Medicine (JEM) 2004 Jul 19;200(2):123-35.

In May 2005, the biotechnology company BioE, based in St. Paul, MN, becomes the first company to commercially market multi-potent stem cells extracted from cord blood. Their "Multi-Lineage Progenitor Cells™ (MLPCs™)" have differentiated into tissues representative of neural stem cells, nerve cells, liver/pancreas precursors, skeletal muscle, fat cells, bone cells and blood vessels.

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Answer: Probably. In the lab, stem cells from umbilical cord blood can be induced to develop into nerve cells. When neural cells derived from blood stem cells are transplanted into lab mice, the cells have been shown to survive and function. The hope is that, eventually, there will be established procedures to infuse cord blood into human beings, get the stem cells to turn into nerve cells, and have those nerve cells function in the body to fix the patient's problem.

Disorders of the Central Nervous System (CNS) which might be treated with stem cells:

• degenerative diseases: Parkinson's, Alzheimer's, Multiple Sclerosis
• traumatic damage: post-stroke, spinal cord injuries
• hereditary diseases: Huntington's, Leukodystrophies

The page on Diseases Treated by Blood Stem Cells sorts CNS diseases according to whether they are in a very experimental stage of research or are undergoing clinical trials with human patients. Also, the News Page chronicles some miraculous cures claimed with cord blood infusions (for example, see the entries for Dec 2004).

Research Report: Multiple Sclerosis
Stem cell transplants as a therapy for Multiple Sclerosis have been in clinical trial for several years. These trials are using autologous stem cells from the patient, not cord blood. The transplants seem to have slowed the progression of MS in some patients. But the transplant itself carries a significant risk of mortality, about 10%, and thus was only tested in patients with severe MS who were not responding to other treatments.

References:

• press release 4/16/2002 from the American Academy of Neurology annual meeting.
• Nash RA, et al. 5/22/2003 Blood. A team led by George Kraft of the Fred Hutchinson Cancer Research Center, Seattle, WA, tried autologous stem cell transplants on 26 MS patients, followed over a period of three years.
• Fassas A, et al. 8/2002, J Neurol. 249(8):1088-97. Researchers in Italy and Greece performed a retrospective study of stem cell transplants in 85 MS patients.

Research Report: Amyotrophic Lateral Sclerosis (ALS; or "Lou Gehrig's Disease")
Cord blood transplants as a therapy for ALS are currently in clinical trial. The ALS Therapy Development Foundation issued a review of "Human Umbilical Cord Blood Therapies in ALS" in Dec. 2002, followed by an update on cord blood; subsequently the Muscular Dystrophy Association opened a clinical trial of cord blood transplant for ALS in 2003.

Research Report: Alzheimer's Disease
In July 2003, the NIH granted $1.4 million over 5 years for research on the conversion of stem cells into neurons. The grant went to the CSO of NewNeural, a privately-held biotech company founded by Dr. Kiminobu Sugaya and two other colleagues; their research works with stem cells from adult bone marrow. In Feb 2005, the University of Central Florida issued a press release that Sugaya's lab, together with colleagues the University of Illinois at Chicago, are the first to demonstrate improved memory in adult animals after transplanting neural stem cells into their brains. The NewNeural team achieved the results by treating bone marrow cells in laboratory cultures with bromodeoxyuridine, a compound that becomes part of DNA, and made adult human stem cells more likely to develop as brain cells after they were implanted in adult rat brains.

Research Report: Stroke
While the news media are reporting miraculous cures that supposedly occured in far-away lands, in the published medical literature the use of stem cells to treat stroke has not advanced beyond mice.

Reference:

• Borlongan CV, Hadman M, Sanberg CD, Sanberg PR 2004: Stroke. 35(10):2385-9
  "Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke." In this study, cord blood stem cells were given intravenously to mice after stroke, together with a drug to help the cells permeate the blood-brain-barrier. Stroke size was dramatically reduced by 40%, and long-term disability was also significantly reduced.

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Answer: Probably. Some hereditary disorders cause the metabolism to gradually destroy the nervous system, as well as damage other organs. One class of hereditary disorders is leukodystrophies, in which the cells sheathing nerves are improperly developed or maintained, and gradually break down. Another class of hereditary disorders is storage disorders, in which cells are damaged by the abnormal accumulation of waste products. There are different types of storage disorders: Mucopolysaccharidoses (MPS) Storage Diseases (includes Hurler's Syndrome, Sanfilippo Syndrome) and Lysosomal Storage Diseases (includes Gaucher Disease, Tay-Sachs).

The team lead by Joanne Kurtzberg, M.D., at Duke University, is conducting trials of cord blood transplants in very young children with various inherited disorders. So far, they have presented successful results with Sanfilippo Syndrome, Hurler's Syndrome, and Krabbe Disease.

References:

• Duke University press release Jan 2004, also presented at American Society of Hematology Dec 2003 meeting
• Medscape CME on Hurler's Syndrome, based on
• Staba, SL, et al., N Engl J Med. 2004; 350:1960-1969. "Cord-blood transplants from unrelated donors in patients with Hurler's syndrome."
• Escolar ML, et al., N Engl J Med. 2005; 352(20):2124-6. "Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease."

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Answers: There are so many YES/MAYBE answers that they have to be enumerated.

Cellular Cardiomyoplasty
This is a new field of medicine in which stem cell transplantation is used to repair or regenerate damaged heart muscle. Animal studies have shown that stem cells from bone marrow can survive in dead heart muscle and improve its ability to contract. As of late 2002, this technique has entered phase I clinical trials with human beings.

In the trials, the stem cells are injected into the perimeter of the dead muscle. Most studies have harvested the stem cells from bone marrow, although blood stem cells have also been harvested by apheresis of the circulating bloodstream. The bone marrow is sometimes injected fresh, or sometimes filtered to increase the percentage of stem cells. So far, many different approachs are being attempted because this field is still in its infancy.

The first molecular evidence that stem cells from cord blood can repair heart damage in transplant patients was announced by researchers at Duke University in Feb 2004.

References:

• Stamm, C. et al. (4Jan2003) The Lancet 361:45-46
• Tse, H.-F. et al. (4Jan2003) The Lancet 361:47-49
• News reports about study results presented at the American Heart Association meeting: CNN 10Nov2003
• Press releases from the American Heart Association: AHA 11Nov2003
• Press release from Duke University, to be presented at the International Association of Bone Marrow Transplantation Research meeting 12-17Feb2004 in Orlando, FL: IBMTR Feb2004
• Web page from the FDA’s BRMAC (Biological Response Modifiers Advisory Committee), dated 15Mar2004, on the clinical development of cellular products to be used in the treatment of heart diseases.
• Wollert, KC et al. (10Jul2004) The Lancet 364(9429):141-8.
  "Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial"
• Botta, R. et al. (Sep2004) FASEB J. 18(12):1392-4.
  "Heart infarct in NOD-SCID mice: therapeutic vasculogenesis by transplantation of human CD34+ cells and low dose CD34+KDR+ cells."

Vascular regeneration
Several research groups are experimenting with cord blood as a raw material for tissue engineering, particularly the development of vascular grafts. There are also reports that diabetic patients with severe damage to peripheral blood vessels (this is called "lower limb ischemia") have been saved from amputation by the infusion of blood stem cells from their own bone marrow.

References:

• Schmidt D et al. (Dec.2004) Ann Thorac Surg. 78(6):2094-8. "Umbilical cord blood derived endothelial progenitor cells for tissue engineering of vascular grafts."
• Press release 6Oct2003 from Aastrom Biosciences announcing SBIR grant from NIH for Phase I Clinical Trial to develop stem cell treatment for in vivo animal model of limb ischemia.
• Yamamoto et al. (Dec2004) Arterioscler Thromb Vasc Biol. 24(12):192-196. "Molecular evaluation of endothelial progenitor cells in patients with ischemic limbs: therapeutic effect by stem cell transplantation."

Skin growth for wound repair
References:

• Valbonesi M, et al. (2004) Transfusion and Apheresis Science. 30:153-156. "Cord blood (CB) stem cells for wound repair. Preliminary report of 2 cases."

Kidney repair
Several research groups (example: U. of Queensland, Australia) are working to take stem cells from bone marrow and elicit them to grow into renal cells. Moreover, donor stem cells are being infused in combination with kidney transplants to reduce patient need for immunosuppressive drugs that prevent organ rejection.

Liver repair
References:

• Kakinuma S, et al., Stem Cells. 2003;21(2):217-27. "Human umbilical cord blood as a source of transplantable hepatic progenitor cells."

Diabetes / Pancreas
References:

• Ende N, Chen R, Reddi AS. (Aug2004) Biochemical and Biophysical Research Communications. 321(1):168-71. "Transplantation of human umbilical cord blood cells improves glycemia and glomerular hypertrophy in type 2 diabetic mice."
• Ende N, Chen R, Reddi AS. (Dec2004) Biochemical and Biophysical Research Communications. 325(3):665-9. "Effect of human umbilical cord blood cells on glycemia and insulitis in type 1 diabetic mice."

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