Bone marrow stem cells may help control inflammatory bowel disease

August 21, 2008

Cell transplants protect intestinal tissue from autoimmune attack in animal model

Massachusetts General Hospital (MGH) investigators have found that infusions of a particular bone marrow stem cell appeared to protect gastrointestinal tissue from autoimmune attack in a mouse model. In their report published in the journal Stem Cells, the team from the MGH Center for Engineering in Medicine report that mesenchymal stem cells (MSCs), known to control several immune system activities, allowed the regeneration of the gastrointestinal lining in mice with a genetic mutation leading to multiorgan autoimmune disease.

"Our findings suggest that MSC therapy could become a useful treatment for inflammatory bowel disease," says Biju Parekkadan, PhD, of the Center for Engineering in Medicine, the paper's lead author. "Several previous studies have observed these cells' ability to inhibit specific subsets of T cells and relieve symptoms in particular autoimmune disorders. But this is the first demonstration of their ability to suppress a broad-based autoimmune reaction and protect gastrointestinal tissue."

Autoimmune disease occurs when the immune system loses control over lymphocytes (white blood cells) that attack an individual's own tissues. Treatments for these diseases - more than 80 conditions, ranging from type 1 diabetes to rheumatoid arthritis to gastrointestinal disorders like Crohn's disease - are primarily directed against symptoms; and even those that target the immune system do not completely suppress the out-of-control response. Found in the bone marrow, MSCs give rise to tissues supporting blood cell development and secrete factors that can modulate several immune system activities. Their use has recently received FDA approval to treat severe graft-versus-host disease in children.

The current study was designed to investigate MSCs' therapeutic potential in a model of multiorgan autoimmune disease. The researchers used a strain of mice in which a genetic mutation leads to deficiency in regulatory T cells, which suppress the activity of self-reactive immune cells, resulting in overwhelming autoimmune disease. The mice were treated with infusions of either MSCs or regulatory T cells, and a week later the researchers examined the effects on tissues from the pancreas, the liver and the distal ileum - the lower end of the small intestine - which are usually attacked by autoimmune reactions.

While little improvement was seen in the pancreatic or liver tissue, in four of the six MSC-treated mice, intestinal tissues appeared almost identical to those of normal mice. Structural defects seen in the intestinal lining of untreated autoimmune mice had disappeared in the MSC-treated mice, an improvement seen in only one of six mice treated with regulatory T cells.

Analysis of the animal's lymph nodes revealed that MSC treatment produced a significant reduction in inflammation. Surprisingly, cell-tracking studies indicated that the MSCs - which were administered by infusion into the peritoneum, the membrane lining the abdominal cavity - moved into abdominal lymph nodes rather than to the intestine itself. The presence of MSCs was associated with a reduction of activated T cells and changes in other indicators of immune system activity, indicating suppression of the out-of-control immune reaction.

"The intestine may be an ideal site for MSC therapy, given its rapid ability to regrow tissue and its extensive local supply of lymph nodes; and the route by which the cells were administered may have ensured a greater amount of engraftment in gut-associated lymph nodes," explains Martin Yarmush, MD, PhD, director of the MGH Center for Engineering in Medicine and senior author of the study. "Before we can think about testing this approach in patients, we need to know more about long-term effects of MSC infusion - including immunosuppressive effects - and gain more understanding of how MSCs modulate immune cell activity in more realistic models of inflammatory bowel disease."

Massachusetts General Hospital

---

---

	Autoimmune: The Cause and The Cure (This book identifies the cause & the cure for: Chronic Fatigue Syndrome, Fibromyalgia, Lupus, Rheumatoid Arthritis, Raynaud's, Rosacea, Myasthenia Gravis, Hashimoto's, Type 2 Diabetes, Multiple Sclerosis, Sjogren's, and more) by Annesse Brockley (Author), Kristin Urdiales (Author) This Book Identifies The Cause And The Cure For: Chronic Fatigue Syndrome, Fibromyalgia, Lupus, Sjogren's, Rheumatoid Arthritis, Raynaud's, Rosacea, Myathenia Gravis, Hashimoto's, Type 2 Diabetes, Multiple Sclerosis, and more.
	The Autoimmune Epidemic by Donna Jackson Nakazawa (Author), Dr. Douglas Kerr (Foreword) From the foreword by Dr. Douglas Kerr, Director, Johns Hopkins Transverse Myelitis Center "The Autoimmune Epidemic by Donna Jackson Nakazawa is an astounding book....It is the kind of book that will rivet you and scare you. It will make you angry. It will amaze you with the courage of some of the people described in the book...The Autoimmune Epidemic is every bit as compelling as Upton Sinclair's The Jungle...It is also every bit as necessary as An Inconvenient Truth.... You will leave this book with no reservations about the veracity of the conclusions: put simply, there is no doubt that autoimmune diseases are on the rise and increasing environmental exposures of toxins and chemicals is fueling this rise. The research is sound. The conclusions unassailable.... Reading The...
	Living Well with Autoimmune Disease: What Your Doctor Doesn't Tell You...That You Need to Know by Mary J. Shomon (Author) A complete guide to understanding the mysterious and often difficult-to-pinpoint disorders of the immune system--and finding the keys to diagnosis, treatment, and recovery. An estimated fifty million people suffer from symptoms including fatigue, joint pains, depression, or heart palpitations — signs that the immune system has turned on itself, causing conditions such as thyroid disease, hepatitis, or multiple sclerosis. And while doctors may prescribe treatments to relieve these surface ailments, when asked about the life-long health implications of an autoimmune condition, they often just shrug their shoulders. Yet much like cancer, having one autoimmune disease puts you at high risk for developing another, and understanding the underlying immune process can reverse a patients...
	The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life by Rita Baron-Faust (Author), Jill Buyon (Author) As featured in the New York Times and recommended by the National Women's Health Resource Center and the Society for Women's Health Research, The Autoimmune Connection discusses the links between autoimmune diseases and offers up-to-date information on diagnosis, treatments, and risks for women with one or more autoimmune disease, such as lupus, rheumatoid arthritis, or Crohn's disease.
	The Bible Cure For Auto-immune Diseases: Ancient truths, natural remedies and the latest findings for your health. (New Bible Cure (Siloam)) by Donald Colbert (Author) You can have a normal, healthy immune system! Having an autoimmune disease, a condition in which the immune system becomes confused and turns the body's attack against itself, is not a life sentence. In this practical, informative book, Dr. Don Colbert offers a natural, scriptural plan for your complete recovery from autoimmune diseases, which afflict about 40 million Americans. Autoimmune diseases such as rheumatoid arthritis, lupus, chronic fatigue syndrome and multiple sclerosis do not have to rob you of the vital health God intended for you to enjoy. You will learn how to: Restore gastrointestinal health Reduce stress Break the link between autoimmune diseases and hormonal imbalances Combat toxic overload Strengthen your immune system You want to be healthy....
	If You Have to Wear an Ugly Dress, Learn to Accessorize: Guidance, Inspiration, and Hope for Women with Lupus, Scleroderma, and Other Autoimmune Illnesses by Linda McNamara (Author), Karen Kemper (Author) "Lupus and scleroderma are our shadows but they do not define us. We may have to wear the ugly dresses of chronic illness but we don't have to be the ugly dresses." -- Linda and Karen If you are experiencing a long-term illness or disability, this book is for you -- as well as your family and friends. The authors share a collection of deeply personal stories and poetry to describe their journey from illness to health, well-being, and fruitful living. Their creative life management strategies provide a road map to help you: overcome overwhelming feelings of loss, grief, anger, fear, and powerlessness; navigate a healthcare system filled with individuals who can be patronizing or dismissive; field well-intentioned but hurtful remarks such as, "But you look so good!" walk the...
	Help, My Body Is Killing Me: Solving The Connections Of Autoimmune Disease To Thyroid Problems, Fibromyalgia, Infertility, Anxiety, Depression, Add/Adhd And More by Dr. Kevin Conners (Author) “Why do I feel so lousy even after my doctor said my labs are normal? “ “I’m exhausted all the time.” “Ever since ______, my life has never been the same.” “My doctor and even my family just think I’m crazy.” “We’ve tried everything to get pregnant and are ready to give up hope.” “I’m on 4 different meds and nothing seems to work.” “My son’s teacher wants him on Ritalin but I know that’s not the solution, but I’m at the end of my rope!”These are just a few questions our patients have that sparked me to write this simple, easy-to-read book that has become an “ah-ha moment” to its readers. It is comforting to know there is a REASON for your symptoms and downright inspiring to find out there is a SOLUTION. My heart breaks to hear the stories of...
	What Your Doctor May Not Tell You About Autoimmune Disorders: The Revolutionary, Drug-Free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic Fatigue; Rheumatoid Arthritis, and Other Diseases by Stephen B. Edelson (Author), Deborah Mitchell (Author) Dr. Edelson discusses the most common types of autoimmune diseases, outlining their symptoms, causes, and risk factors. He describes his own revolutionary program for treating the root of all autoimmune disorders--without drugs--providing readers with new hope for getting back on the road to better health.
	Women and Autoimmune Disease : The Mysterious Ways Your Body Betrays Itself by Robert G. Lahita (Author) Autoimmune diseases -- including chronic fatigue syndrome, vasculitis, juvenile diabetes, alopecia, Graves' disease, Sj#246;gren's syndrome, lupus, rheumatoid arthritis, and multiple sclerosis -- are among the hottest topics in the medical community. Although these diseases express themselves in different ways, in all of them, the body's immune system begins to attack normally functioning, healthy cells. Despite the recent surge in interest and research, these fascinating diseases are highly mysterious, frequently misdiagnosed, and controversial in cause and treatment. They are often interconnected in ways that are both misunderstood and life-threatening. And one of the biggest puzzles is why 80 percent of autoimmune disease sufferers are women. In this authoritative yet thoroughly...
	Women, Work, and Autoimmune Disease: Keep Working, Girlfriend! by Rosalind Joffe (Author), Joan Friedlander (Author), L.G. Mansfield (Editor) When a woman receives a life-changing diagnosis of a serious, chronic illness, her first instinct may be to quit the workforce. This may bring a strong sense of relief initially, but as her disease becomes manageable, work is again desirable. Women, Work, and Autoimmune Disease urges women so affected to stay employed in order to preserve their independence and sense of self. Filled with tips, tricks, and first-person accounts, this book is a resounding call for self-reliance and resilience. Authors Rosalind Joffe and Joan Friedlander identity the factors that make working particularly difficult for women with autoimmune disease, and then offer practical suggestions to address them. Exploring such issues as the complexities of autoimmune diseases and the correlation between disease,...