Part 1

The Promise of Adult Stem Cells

J. C. Willke, M.D.

Adult stem cells have actually been used since 1968, when the first bone marrow transplants were done to help cure leukemia. At the time, those doing these transfusions had not isolated the active cells. It took two more decades before a scientist in Wisconsin isolated the active cells from bone marrow and called them adult stem cells. Since that time, there has been an amazing cascade of continuing new developments in this field.[1]

There are three types of stem cells: embryonic, adult, and those obtained from umbilical cord, placenta, and Wharton’s jelly, which surrounds the three umbilical cord blood vessels connecting the fetus to the mother.[2] Stem cells are the basic primitive beginnings of all the different cell types in the organs of our body. This ability to develop into different cell types is characterized as omnipotent and pleuripotent.

Before we get into their function and uses, we must first review the known physiological facts. It is a simple scientific fact that each of you reading these words once was a single cell, a fertilized egg, a zygote, and that all you have done since that time is to grow up. As a single cell, you were already human (not a rabbit). You were already sexed (X and Y chromosomes), you were already alive (not dead—you were growing), and you were complete, for nothing has been added to the single cell each of you once were but nutrition and oxygen. Therefore, from a biological, scientific standpoint, it is impossible to draw a line in time from that first cell until the old man dies and say that before this “it,” the entity was not human life, but after “it” he was. Even so, in the face of this obvious fact, many people do disagree and decry the “five-day-old ball of a hundred cells,” stating that these do not look human. But of course, this is exactly what a five-day-old human, which you once were, looks like.

Where did these cells come from? In order to get embryonic stem cells, one must take a five-day-old living human embryo, cut him or her open, and remove embryonic stem cells from the inside. This of course kills this living human and is the basis for the ethical objection to this procedure.

Stem Cells and Conventional Wisdom

Adult stem cells are present in every organ of our body. It is these cells that produce the new growth that repairs injury and replaces dying cells. Umbilical cord cells are usually grouped with adult stem cells, as are stem cells taken from the placenta. The difference from embryonic ones is that adult stem cells are taken from the patient, cultured, and returned to the same individual. Umbilical cord stem cells come from another individual, the newborn infant, but are so primitive that they can often successfully be used in another human.

Just a few years ago, conventional wisdom held that adult stem cells are not as “plastic” as embryonic stem cells—that is, they cannot turn into as many different cell types and organs—and that adult stem cells are much more difficult to obtain and grow, whereas embryonic stem cells can be obtained in some quantities from “spare” frozen embryos. But this conventional wisdom has been completely replaced by recent advances. Adult stem cells are being discovered in one new organ after another. They are very plentiful in fat, skin, and multiple other organs.

Adult stem cells culture just as easily as embryonic ones, so this original objection no longer holds. Adult stem cells, perhaps to the surprise of most researchers, are being shown to be just as “plastic” and just as versatile as embryonic stem cells. New information and research in the last few years has been consistently showing that in one cell type after another, adult stem cells are capable of turning into (probably) all types of human cells, including those in the central nervous system.

Over the last two or three years, hardly a week has gone by but that I do not receive another report of a research advance using adult and umbilical cord stem cells.

There are currently over 1,100 clinical trials approved by the Food and Drug Administration going on in the United States alone using adult stem cells. These are being used to treat over seventy different human diseases and injuries. To date, embryonic stem cells are being used in animal experimentations, but nothing yet has been done with embryonic stem cells in humans.

Adult Stem Cell Breakthroughs

Let us itemize very briefly these breakthroughs.

• Spinal cord: Dr. Carlos Lima in Lisbon, Portugal, recently published his treatment of a number of patients who are paraplegic or tetraplegic following spinal cord injury. He took stem cells from the patient’s own olfactory (nasal) mucosal lining, cultured them, and then grafted them onto the site of the injury.[3] MRI scans later showed that the grafts had taken. All of the patients within a year and a half have shown definite improvement of motor function.
• Parkinson’s disease: Using the patient’s own stem cells, University of Kentucky scientists successfully treated ten Parkinson’s patients.[4] Two earlier studies in 2002 in England reported improvement in five patients.[5]
• Heart tissue regeneration: Adult stem cells have been shown to be capable of repairing cardiac tissue after heart attacks, even some length of time later. These studies involved obtaining adult stem cells from that patient’s body, culturing them, and then transplanting them into the coronary artery feeding the location of the heart attack or being injected into the heart muscle. Results of three recent studies all show heart function substantially improved.[6] Using the amniotic fluid that cushions a baby in the womb, fetal stem cells have been isolated, cultured, and then placed on a mold of biodegradable plastic. In one month, valves have been created.[7] Adult human cells from bone marrow were able to regenerate and self-repair damaged heart muscle.[8] Baxter International is using adult stem cells to treat 150 patients to create new blood vessels in their cardiovascular system. Small earlier studies showed substantial improvement of function.
• Bone repair: Adult stem cells derived from the fat cells of a seven-year-old girl were used to successfully regrow a skull bone defect. Skull bones normally do not regenerate; therefore metal plates are used to cover defects. This girl had a defect totaling nineteen square inches. Bits of her own bone mixed with her own fat-derived stem cells were applied to the surface of the brain, resulting in the regeneration of a bony skullcap.[9] In addition, a number of studies have used the patient’s own adult stem cells to successfully stimulate repair of non-healing fractures.[10]
• Eyes: Limbal adult stem cells, transplanted onto corneas damaged from disease or chemical accidents, showed recovery of sight in the majority of patients.[11]
• Urinary tract: Female patients suffering from stress urinary incontinence were successfully treated with their own muscle-derived adult stem cells.[12] Doctors at Children’s Hospital in Harvard Medical School have succeeded in using a patient’s own adult stem cells to grow a fully functioning bladder.[13]
• Diabetes: Adult stem cells have successfully increased insulin production in mice with type II diabetes.[14] Human trials will begin shortly. Researchers in the United Kingdom have created insulin-producing cells for diabetic patients from adult stem cells in umbilical cord blood.[15] In Argentina, stem cells from a diabetic patient’s own bone marrow was fed into his pancreas through an artery. Glucose levels returned to normal without medication.[16]
• Lupus Erythematosus: Autologous non-myeloablative hematopoietic stem cell transplantation was done using the affected patient’s own adult stem cells. This life-threatening autoimmune disease was essentially cured in 50 percent of the patients who received such adult stem cells transplants.[17]
• Sickle cell anemia: Patients suffering from sickle cell anemia are being successfully treated with cord blood transplants. This was first done in 1998. The adult stem cells from the donated cord blood successfully replenished the patient’s blood with healthy cells.[18]
• Crohn’s disease: Patients with Crohn’s disease have apparently been cured after treatment with stem cells from their own blood.[19]
• Muscular dystrophy: Out of Milan, Italy, at the San Raffaele Institute, has come research in dogs on muscular dystrophy. Published in the journal Nature, the study used adult stem cells in the treatment with substantial alleviation of weakness and other symptoms.[20]
• ALS (Lou Gehrig’s disease): Amyotrophic lateral sclerosis (ALS) has been treated in rats at Johns Hopkins by transplanting adult stem cells into their spinal cords.[21]
• Cystic fibrosis: Adult stem cells from umbilical cord blood have just been used at the Clinical Cell Therapy Lab at the University of Minnesota Medical Center. These have been differentiated into type 2 alveolar cells, which line the lung air pockets. This is a first step in developing the use of these cells for treating cystic fibrosis.[22]
• Cartilage: Researchers at Children’s Hospital in Pittsburgh have successfully coaxed adult muscle stem cells to change into cartilage. Although it was done in rats, the next step will be human trials, again using adult muscle stem cells.[23]
• Multiple sclerosis: In one study, injection of adult stem cells into patients with malignant multiple sclerosis gave significant improvement.[24]
• Rheumatoid arthritis: A fifty-two-year-old woman with rheumatoid arthritis in twenty-eight joints was treated with adult stem cells. Within a year, her morning stiffness ceased. The study concluded, “This may be performed safely without the development of graft vs. host disease or serious infection.”[25]
• Stroke: Very small embryonic-like stem cells mobilize into the blood stream to help repair damaged tissue from a stroke.[26]
• Skin therapy: Adult stem cells hold a promise to treating baldness in humans. A study at the University of Pennsylvania reports using them to grow hair on bald mice.[27]
• Reconstructive surgery: Chicago researchers are looking at a new adult stem cell technique that will replace implants for reconstructive surgery and body augmentation. This could have profound commercial implications for cosmetic surgery.[28]
• Autoimmune disorders: Ninety percent of nineteen patients with various autoimmune disorders are in remission or have improved after treatment with their own blood stem cells.[29]
• Teeth: New York scientists are exploring the possibility of using adult stem cells to regenerate teeth that have been removed.[30] The pulp of baby teeth contains up to two dozen adult stem cells that appear to be more versatile and longer-lived than many other adult stem cells.[31]

Summary

Only a few years ago, embryonic stem cells were thought to be far superior to adult stem cells. The only major problem voiced was the fact that they could be obtained only by “harvesting” (direct killing) five-day-old human embryos to obtain these cells. For those unconcerned about such destruction of human life, this offered a social problem, not a medical one.

As is obvious from the above litany, in the last few years, there has been an explosion of research on adult stem cells. We now know that there is no problem obtaining large numbers of these cells and that it can be done in a totally ethical fashion. We now know that adult stem cells have been obtained from most major body organs, and if progress continues, we may someday find them in every cell type. Furthermore, we are becoming more skilled at isolating these cells. The use of adult stem cells, as has been shown, offers no problem with host immunity as the cells come from a particular human being and are returned to that same individual. The use in this fashion of adult stem cells also obviates the risk of transmitting infection from host to recipient, as one cannot give oneself an infection.

As for plasticity, the above demonstrates very clearly that adult and cord blood stem cells are now being teased into creating a broad array of various cell types. If such progress continues, it holds promise of being able to use adult stem cells to possibly create all of the cell types in the human body.

It should be obvious to any observer that significant research advances in this field are being reported literally every few weeks. This is a frontier that is only now being opened up, and it is fair to assume that far greater progress will be made in the next few years.

In the face of the success of adult stem cells and the fact that embryonic stem cells have not made any breakthroughs, it is interesting that increasingly large amounts of government money are being funneled into embryonic stem cell research with very little going into adult stem cell research. In contrast, almost all of the above adult research has been done with private funding. Does private venture capital know something that our elected officials do not?

[2] The Toronto Star reported that University of Toronto scientists found a “jackpot” of stem cells in Wharton’s jelly (Joseph Hall, “U of T team discovers stem cell jackpot,” Toronto Star, Feb. 9, 2005, A01).

[3] Laurance Johnston and Sara Sa, “Olfactory Tissue Transplantation for SCI: Portugal Clinical Trials”; C. Lima et al., “Olfactory Mucosa Autografts in Human Spinal Cord Injury: A Pilot Clinical Study,” Journal of Spinal Cord Medicine 29 (2006): 191–203.

[4] John T.Slevin et al., “Improvement of bilateral motor functions on patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor,” Journal of Neurosurgery 102 (Feb. 2005): 216–222.

[5] Steven S. Gill et al., “Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease,” Nature Medicine 9 (May 2003): 589–595.

[6] Amit N. Patel et al., “Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study,” Journal of Thoracic and Cardiovascular Surgery 130 (Dec. 2005): 1631–1638; J. Joseph et al, “Safety and effectiveness of granulocyte-colony stimulating factor in mobilizing stem cells and improving cytokine profile in advanced chronic heart failure,” American Journal of Cardiology 97 (Mar. 1, 2006): 681–684; Bodo E. Strauer et al, “Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study,” Journal of the American College of Cardiology 46, no. 9 (Nov. 1, 2005): 1651–1658.

[7] This was reported at the American Heart Association Conference in Chicago on November 11, 2006.

[8] Young-sup Yoon et al, “Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction,” Journal of Clinical Investigation 115, no. 2 (Feb. 1, 2005): 326–338.

[9] “Stem cells from fat used to repair girl’s skull,” Associated Press, Dec. 20, 2004.

[10] Celia Hall, “Stem Cells Help Broken Bones Heal,” London Daily Telegraph, July 29, 2006; P. H. Warnke et al., “Growth and Transplantation of a Custom Vascularised Bone Graft in a Man,” Lancet 364 (Aug. 28, 2004): 766–770.

[11] T. Inatomi et al., “Midterm Results on Ocular Surface Reconstruction Using Cultivated Autologous Oral Mucosal Epithelial Transplantation,” American Journal of Ophthalmology 141, no. 2 (Feb. 2006): 267–275; E. J. Holland et al., “Management of Aniridic Keratopathy With Keratolimbal Allograft: a Limbal Stem Cell Transplantation Technique,” Ophthalmology 110, no. 1 (Jan. 2003): 125–130.

[12] Carr, L., et al., “Muscle Derived Cell Injection Technique to Optimize the Treatment of Stress Urinary Incontinence,” American Urological Association annual meeting, Abstract #1185, May 23, 2006.

[13] Hilary White, “Complete Bladders Grown from Patients’ Own Cells,” Lifesite.net, Apr. 4, 2006.

[14] “Stem cell cure hope for diabetes,” BBC, Nov. 12, 2006.

[15] Steven Ertelt, “Adult Stem Cell Research Breakthrough Produces Insulin for Diabetics,” LifeNews.com, July 10, 2006.

[16] “Stem cells implanted into pancreas of diabetic patient through an artery, Argentina,” Stem Cell Research Medical and Health News, Feb. 9, 2005.

[17] Richard K. Burt “Nonmyeloablative Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus,” Journal of the American Medical Association 295, no. 5 (Feb. 1, 2006): 559–560.

[18] Christiane Vermylen, “Hematopoietic Stem Cell Transplantation in Sickle Cell Disease,” Blood 17, no. 3 (Sept. 17, 2003): 163–166; “60 Minutes II: Holy Grail,” CBS News, June 5, 2002.

[19] “Crohn’s Disease: Hematopoietic Stem Cell Transplantation is Option for Patients with Severe CD,” Blood Weekly, 23, Nov. 31, 2003.

[20] Maurilio Sampaolesi et al., “Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs,” Nature 444, no. 7117 (Nov. 16, 2006): 574–579.

[21] Leyan Xu et al., “Human Neural Stem Cell Grafts Ameliorate Motor Neuron Disease in SOD-1 Transgenic Rats,” Transplantation 82, no. 7 (Oct. 15, 2006): 865–875.

[22] “U of M Researchers Turn Cord Blood Into Lung Cells,” University of Minnesota, Nov. 1, 2006; Byron Spice, “Stem Cell Therapy for Cystic Fibrosis?” Pittsburgh Post-Gazette, Dec. 21, 2004.

[23] Ryosuke Kuroda et al., “Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells,” Journal of Arthritis and Rheumatism 54, no. 2 (Feb. 2006): 433–442.

[24] G. L. Mancardi et al., “Autologous Stem Cell Transplantation as Rescue Therapy in Malignant Forms of Multiple Sclerosis,” Multiple Sclerosis 11, no. 3 (June 2005): 367–371.

[25] Richard K. Burt et al., “Introduction of Remission of Severe and Refractory Rheumatoid Arthritis by Allogeneic Mixed Chimerism,” Journal of Arthritis and Rheumatism 50, no. 8 (Aug. 2004): 2466–2470.

[26] M. Z. Ratajczak et al., “New Directions in Stem Cell Research,” Leukemia 20 (2006): 18–28; Woei-Cherng Shyu et al., “Granulocyte Colony-stimulating Factor for Acute Ischemic Stroke: A Randomized Controlled Trial,” Canadian Medical Association Journal 174, no. 7 (Mar. 28, 2006): 927-933; C. S. Stilley et al., “Changes in Cognitive Function after Neuronal Cell Transplantation for Basal Ganglia Stroke,” Neurology 63, no. 7 (Oct. 2004): 1320–1322; M. Y. Gordon et al., “Characterization and Clinical Application of Human CD34+ Stem/Progenitor Cell Populations Mobilized into the Blood by G-CSF,” Stem Cells 24, no. 7 (July 2006): 1822–1830.

[27] Rebecca Morris et al., “Capturing and Profiling Adult Hair Follicle Stem Cells,” Nature Biotechnology 22, no. 4 (Apr. 2004): 411–417.

[28] Steven Reinberg, “Stem Cells Promise Better Plastic Surgery,” Forbes.com, Feb. 17, 2005.

[29] Oliver Rosen et al., “Autologous Stem-Cell Transplantation in Refractory Autoimmune Diseases After in Vivo Immunoablation and Ex Vivo Depletion of Mononuclear Cells,” Arthritis Research 2, no. 4 (Feb. 2000): 327–336.

[30] M. T. Duailibi et al., “Bioengineered Teeth from Cultured Rat Tooth Bud Cells,” Journal of Dental Research 83, no. 7 (2004): 523–528.

[31] Brian Vastag, “Baby Teeth Pulp Stem Cells,” Journal of the American Medical Association 289, no. 19 (May 21, 2003): 2491; Masako Miura et al., “SHED: Stem Cells From Human Exfoliated Deciduous Teeth,” Proceeding of the National Academy of Sciences 100, no. 10 (May 13, 2003): 5807–5812.

NEXT: Shane G. Smith responds to J. C. Willke.