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IN HUMAN PATIENTS:

Patient’s Own Cells Aid Spinal Cord Repair

Eighteen-year old Melissa Holley, a paraplegic patient with a severed spinal cord, has been treated with her own immune cells, and has regained movement of her toes and bladder control.

Reference: Globe and Mail (Toronto), June 15, 2001.

Symptoms of Parkinson's disease in a San Clemente, Calif., man have "largely disappeared" after doctors removed stem cells from his brain, grew them into neurons and transplanted the neurons back into his brain, the Washington Post reports.  The procedure, described April 8, 2002 at a meeting of the American Association of Neurological Surgeons, marks the first in which doctors transplanted "adult neural stem cells" -- stem cells that can "morph into every kind of brain cell" -- to a human.  The neural stem cells may allow patients with Parkinson's to  "essentially grow their own cures," the Post reports.  As part of the procedure, Michel Levesque, a neurosurgeon at Cedars-Sinai Medical Center in Los Angeles, removed 50 to 100 cells from the brain of the San Clemente patient and grew them in the lab for a few months. Levesque injected about six million of the cells, 35% of which were neurons, back into the man's brain. …After a year, the man's symptoms were relieved by 83% …

Reference: American Health Line, April 10, 2002.

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Adult Stem Cells Treat Multiple Sclerosis

Researchers have developed a combined therapy using a patient’s own stem cells for treatment of severe cases of multiple sclerosis. Treatment decreased tissue damage in the patients, and had the capacity to completely suppress further tissue damage, an effect that appears to be sustained with time.

Reference: G.L. Mancardi et al., "Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS," Neurology 57, 62-68; July 10, 2000.

Scientists reported April 16 that transplantation of stem cells from a patient’s own blood could provide a new treatment for people with severe cases of multiple sclerosis. In research presented at the American Academy of Neurology’s annual meeting, researchers at the University of Washington Medical Center in Seattle reported treating 26 patients with severe MS with their own adult stem cells. Conventional treatments had previously been unsuccessful for all of the patients. After the transplant of their own adult stem cells, 20 patients were stabilized, and 6 patients showed improvement in their condition. "This is good news," said Dr. George Kraft. "These patients had all been rapidly deteriorating over the past year, so to get them to a point where they are stabilized is great progress."

Reference: Liz Kay, "Stem Cell Therapy May Help Multiple Sclerosis", Los Angeles Times, April 17, 2002.

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Adult Stem Cells Successfully Treat Heart Disease

The first reports of successful treatment for heart disease using the patient’s own adult muscle stem cells after heart attack are encouraging news. French physicians implanted skeletal muscle stem cells back into the patient; the encouraging result after eight months’ follow-up underlines the potential of this new approach. Further clinical trials are now underway in Europe and the U.S. for other patients with heart disease. No human trials using embryonic stem cells have ever been reported.

A review of potential heart treatments notes that cell transplantation is a potential therapeutic approach for patients with chronic heart failure. Experimental transplantation of muscle cells showed that the grafted cells can functionally integrate with and augment the function of the recipient heart. The scientists note that skeletal muscle stem cells are abundant and can be grafted successfully into the patient’s own heart even after genetic manipulation in vitro.

References: P. Menasché et al., ["Autologous skeletal myoblast transplantation for cardiac insufficiency. First clinical case" (article in French)], Arch Mal Coeur Vaiss 94(3), 180-182, March 2001.

"Doctor Puts Arm Muscle Cells Into Patient's Heart," Associated Press, May 30, 2001.

"First Percutaneous Endovascular Case of Heart Muscle Regeneration Completed with Bioheart's MyoCell(TM) Product," PRNewswire, May 30, 2001.

R.M. El Oakley et al., "Myocyte transplantation for cardiac repair: A few good cells can mend a broken heart," Annals of Thoracic Surgery 71, 1724 –1733, 2001.

Doctors in Germany report the successful use of a patient’s own adult stem cells from bone marrow to regenerate tissue damaged after a heart attack. They injected the man’s own bone marrow stem cells into his damaged heart muscle. Ten weeks later, the damaged area of heart tissue had been reduced, replaced by new cells, and heart function had increased by 20-30 %. The authors conclude "transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after… infarction." They also point out that the therapeutic benefits can be ascribed to the adult stem cells. They plan to perform the same operation on 20 more patients in the coming months. The use of the patient’s own adult stem cells from bone marrow or muscle to treat damage from heart attack is also in clinical trials in France and the U.S. (Reuters Health, July 23, 2001).

Reference: B.E. Strauer et al., "Myocardial regeneration after intracoronary transplantation of human autologous stem cells following acute myocardial infarction," Dtsch Med Wochenschr 126, 932-938; Aug. 24, 2001.

Surgeons at Newcastle's John Hunter Hospital north of Sydney extracted stem cells from patient Jim Nichol's bone marrow then injected them back into his heart wall to stimulate blood vessel growth in areas which lacked sufficient blood supply. Nichol was discharged from hospital on Tuesday and his condition will be monitored over the next six months by researchers who undertook the trial as part of an international experiment also being carried out in Hong Kong and China.

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Adult Stem Cells Used In Stroke Treatment
In a follow-up study, stroke patients who had received a transplant of human neuronal cells showed improved brain cellular function and engraftment of the implanted adult stem cell line.  The cultured cell line was originally derived from an adult tumor (a "teratocarcinoma", sometimes called an "embryonal carcinoma" because it mimics some characteristics of embryonic cells;  the tumor had been "tamed" and grown in culture a number of years.)

References:  C.C. Meltzer et al., "Serial [18F]Fluorodeoxyglucose Positron Emission Tomography after Human Neuronal Implantation for Stroke,"  Neurosurgery 49, 586-592;  2001.

D. Kondziolka  et al., "Transplantation of cultured human neuronal cells for patients with stroke, Neurology 55, 565-569;  Aug.  2000.

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Adult Stem Cells Help Restore Sight

Corneal stem cells have been used by doctors in Japan to restore useful vision to patients who were legally blind. Transplants of adult corneal stem cells were used for conditions in which normal cornea transplants were unsuitable. One year after treatment, over half of patients had marked improvements in vision.

Reference: K. Tsubota, et al,"Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation," New England Journal of Medicine 340, 1697-1703, June 3, 1999

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Umbilical Cord Blood Stem Cells Treat Sickle Cell Anemia
Umbilical cord blood stem cells have been used successfully to treat sickle cell anemia.  The cord blood came from a matched sibling of the patient.  The researchers note that routine collection of umbilical cord blood from siblings should be considered for sickle cell disease cases.

Reference: L. Gore et al.,  "Successful cord blood transplantation for sickle cell anemia from a sibling who is human leukocyte antigen-identical: implications for comprehensive care," Journal of Pediatric Hematology and Oncology 22, 437-440; Sept-Oct 2000.

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Adult Stem Cells Treat Potentially Fatal Skin Disorder
A man with scleromyxedema, a rare and potentially fatal skin disease, is reported free of symptoms after receiving a transplant of adult stem cells taken from his own bone marrow. Like scleroderma, scleromyxedema causes the skin to thicken and become hard. Prior to the adult stem cell treatment, the patient could not completely close his eyes, and had lost the ability to eat. Three months after treatment the patient could once again close his eyes and open his mouth to eat. The results are reported in the August issue of Archives of Dermatology

References: A.M. Feasel et al., "Complete remission of scleromyxedema following autologous stem cell transplantation," Archives of Dermatology 137, 1071-1072; Aug. 2001.

"Stem Cell Transplant Treats Rare Skin Disorder," Reuters Health, August 17, 2001.

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Adult Stem Cells Used to Treat Children with Cartilage Defect 

Bone marrow-derived stem cells have been used clinically to treat children with osteogenesis imperfecta, a condition that leads to multiple fractures, severe bony deformities, and considerably shortened stature. Three months after treatment, the three children showed changes indicating new dense bone formation. The report by researchers at St. Jude Children’s Hospital in Memphis indicates the promising possibility for treatment of this as well as similar stem cell disorders. 

Reference: E. M. Horwitz, et al, "Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta," Nature Medicine 5, 309-313, March 1999 

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Adult Stem Cells Successfully Treat SCIDS

As reported in April 2000 in the journal Science, French scientists restored the immune systems of 3 infants with severe combined immunodeficiency syndrome (SIDS, the "bubble boy syndrome") using gene therapy with the patients’ own bone marrow stem cells. Researchers removed stem cells from the infants' bone marrow, added a working copy of the gene to the cells' DNA, and injected the repaired stem cells back into the infants. Since the procedure used the patients' own cells, there was no problem of transplant rejection. After treatment, the numbers and function of the patients' immune cells were restored to normal levels, and the children were living at home and developing normally with no further treatment

Reference: M. Cavazzana-Calvo, et al., "Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease," Science 288, 669-672, April 28, 2000).

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Adult Stem Cells Show Success Treating Autoimmune Diseases

Physicians at Chicago's Northwestern Memorial Hospital report initial success in using adult stem cells to treat two patients with Crohn's disease, a potentially disabling inflammatory bowel disease. One patient was said to be doing "phenomenally well" 2 ½ months after undergoing the procedure using the adult stem cells, which were extracted from her blood, leading doctors to try it on a second patient. Results in both patients were very encouraging, according to Dr. Richard Burt, who performed the procedures. Burt noted that results of similar procedures on multiple sclerosis patients have also shown progress, and that adult stem cell therapy on patients with lupus had repaired damage to their organs. According to Burt: " 'If you're able to use your own stem cells,' the embryonic stem cell issue is 'not just ethically moot, it's practically moot.' "

Reference:  "Adult Stem Cells Hold Hope for Autoimmune Patients," Reuters Health, Aug. 13, 2001.

In Animal Studies:

Adult Stem Cells Repair Spinal Cord Damage

Several labs have shown adult stem cells capable of re-growth and reconnection in spinal cord injury, allowing functional recovery. Adult stem cell transplants "promote functional recovery of paraplegic adult rats and long-distance motor axon regeneration in their completely transected [severed] spinal cords," and showed "dramatic functional improvement and anatomical repair" (Ramon-Cueto et al; 2000).

Others, using transplanted adult stem cells or injection of growth proteins to stimulate existing adult stem cells, achieved re-growth of neurons and re-myelination (sheathing) of neurons.

References: M. Sasaki et al., "Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons," Glia 35, 26-34; July 2001

Ramon-Cueto et al., "Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia," Neuron 25, 425-435; February 2000.

M.S. Ramer et al.; "Functional regeneration of sensory axons into the adult spinal cord," Nature 403, 312-316; January 20, 2000.

S. Shihabuddin et al.; "Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus," J Neuroscience 20, 8727-8735; December 2000.

Barnett et al.; "Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons," Brain 123, 1581-1588, August 2000.

Ramon-Cueto et al., "Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glial transplants," J Neuroscience 18, 3803-3815; May 15, 1998.

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Adult Stem Cells Used in Stroke Treatment

Adult bone marrow or umbilical cord blood stem cells, delivered intravenously to brain tissue which has suffered stroke damage in rats, provide therapeutic benefit after stroke. The cells appeared to "home" to sites of damage.

References:  J.Chen et al., "Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats," Stroke 32, 2682-2688; November 2001.

J. Chen et al., "Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats," Stroke 32, 1005-1011; April 2001.

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Adult Stem Cells Treat Heart Disease

Bone marrow stem cells injected into heart or which migrate to site of heart damage can regenerate heart tissue.

References: D.Orlic et al., "Mobilized bone marrow cells repair the infarcted heart, improving function and survival," Proceedings of the National Academy of Sciences USA 98, 10344-10349, August 28, 2001

K.A. Jackson et al., "Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells," Journal of Clinical Investigation 107, 1395-1402; June 2001

D. Orlic et al., "Bone marrow cells regenerate infarcted myocardium," Nature 410, 701-705; April 5, 2001

A.A. Kocher et al., "Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function," Nature Medicine 7, 430-436; April 2001.

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Adult Stem Cells Successfully Treat Diabetes

Scientists "retrained" immune cells to reverse diabetes in mice. The autoimmunity that was previously directed against insulin-secreting cells was reversed, and adult stem cells in the mice formed insulin-secreting cells. The treatment was "…thus able to effect an apparent cure of established Type 1 diabetes in the [diabetic] mouse".

Reference: S. Ryu et al.; "Reversal of established autoimmune diabetes by restoration of endogenous ß cell function," J. Clin. Invest. 108, 63-72; July 2001

Pancreatic adult stem cells grown in culture formed insulin-secreting islets. When injected into diabetic mice, the mice survived without further need of insulin injections.

Reference: V.K. Ramiya et al.; "Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells," Nature Medicine 6, 278-282, March 2000.


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