Monthly Archives: December 2012

Ontario man’s sight restored with help of stem cells

Image When Taylor Binns slowly began going blind because of complications with his contact lenses, he started to prepare for living the rest of his life without vision. But an innovative treatment using stem cells has changed all that, and returned to him the gift of sight.

Four years ago, while on a humanitarian work mission to Haiti, Binns developed intense eye pain and increasingly blurry vision. Doctors at home couldn’t figure out what was wrong and, over the next two years, Binns slowly went legally blind, no longer able to drive or read from his textbooks at Queens University, where he was studying commerce.

“Everything you could do before was being taken away, day by day, and it got worse and worse,” he recalls.

Doctors finally diagnosed him with a rare eye disease called corneal limbal stem cell deficiency, which was causing the normal cells on Binns’ corneas to be replaced with scar tissue, leading to painful eye ulcers that clouded over his corneas.

A variety of things can cause the condition, including chemical and thermal burns to the corneas, which are the glass “domes” over the coloured part of our eyes. But it’s also thought that microbial infections and wearing daily wear contact lenses for too long without properly disinfecting them can lead to the disease, too.

Since a corneal transplant was not an option for Binns, hisdoctors at Toronto Western Hospital proposed something new: a limbal stem cell transplant.

The limbus is the border area between the cornea and the whites of the eye where the eye normally creates new epithelial cells. Since Binns’ limbus was damaged, doctors hoped that giving him healthy limbal cells from a donor would cause healthy new cells to grow over the surface.

While the treatment is available in certain centres around the U.S., Binns became the first patient to try the treatment at a new program at Toronto WesternHospital.

Though Binns knew he’d need to take anti-rejection drugs, he decided the procedure was worth a try.

“The alternative was to live in constant pain all my life,” he says. “So there really wasn’t anything to lose.”

Just like with an organ transplant, Binns’ doctors had to find a healthy match. It turned out his younger sister, Victoria, was the ideal candidate for the job.

In the operating room, doctors removed the scar tissue on Taylor’s eyes, then took some healthy stem cells from Victoria’s eyes and stitched them to the surface of Binns’ eyes. 

“Within a month he could see 20/40,” says ophthalmologist Dr. Allan Slomovic. “His last visit he was 20/20 and 20/40.”

Slomovic says “it’s extremely exciting” that the procedure was a success, “especially when you realize there is really nothing else that would have worked for him.”

Binns is now living pain-free, returning to doing everything he used to before his three-year sight loss.

“Being able to see my computer, being able to go for a walk or a drive — I am so happy for that,” he says.

The Toronto team hopes to do many more of these procedures in the future, says Dr. Sherif El Defrawy from the Canadian Ophthalmological Society and University of Toronto’s ophthalmology department.

“We are already seeing this in a number of centres across the country and you will see it more and more as we understand how to improve the success rate,” he says.

Researchers are also working on using stem cells from deceased donors and even using limbal stem cells from a patient’s own eyes. While that would require growing the cells in a lab to force them to multiply, it would also mean that patients might be able to skip anti-rejection drugs.

For Binns, the experience has been life-changing in one more important way: He has now decided to switch his studies from commerce to medicine, and hopes to go to school to become an ophthalmologist.

Toronto Western Hospital has done 6 similar procedures since Binns was treated and all were successful. Most of those patients had suffered burns to their eyes from chemical injuries and some people had been living with birth defects of the surface of the eye.

All stem cell transplants came from a living related donor.

Read more: http://www.ctvnews.ca/health/ontario-man-s-sight-restored-with-help-of-stem-cells-1.1088888#ixzz2FmwHals4

 

Source: CTV News, Avis Favaro, Elizabeth St. Philip

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Pre-Transplant Umbilical Cord Blood Expansion in Lab Speeds Establishment of New Blood Supply in Patients, Reducing High-Risk Time to Recovery

UmbilicalCordBlood Donated umbilical cord blood establishes a new blood supply in patients more quickly after transplantation when it is first expanded in the lab on a bed of cells that mimics conditions in the bone marrow, researchers report in the Dec. 13 edition of the New England Journal of Medicine.

The phase 1/2 study led by scientists at The University of Texas MD Anderson Cancer Center addresses the main difficulty with using umbilical cord blood stem cells to replace the blood supply of patients who have had theirs destroyed by chemotherapy or radiation to treat leukemia, lymphoma and other blood-based diseases.

“You get fewer cells — blood stem cells, immune cells — from two umbilical cords than you do by collecting from a donor’s bone marrow or peripheral blood,” said senior author Elizabeth Shpall, M.D., professor in MD Anderson’s Department of Stem Cell Transplantation and Cellular Therapy.

That lengthens the time between infusion of the cord blood cells and establishment, or engraftment, of the new blood supply. “It’s a high-risk time, patients don’t have white blood cells to fight infection, they don’t have platelets to keep them from bleeding,” Shpall said.

More cells transplanted, faster recovery

By taking blood from one of the two donated umbilical cords and growing it in the laboratory on a bed of mesenchymal precursor cells, the researchers greatly increased the number of cells transplanted, reduced recovery time and increased the proportion of patients whose new blood became established.

“Expansion achieved a median 12-fold increase in total cells transplanted and a 40-fold increase in the number of CD34+ cells, which are crucial for engraftment,” Shpall said. “This led to faster engraftment of white blood cells and platelets, which we believe enhances patient safety.”

“Pre-transplant cord blood expansion on mesenchymal stromal cells could become the new standard of care if our findings are confirmed in a randomized clinical trial,” Shpall said.

Shpall notes that readily available mesenchymal precursor cells provided by Australian regenerative medicine company Mesoblast Limited reduced the time it takes to expand the cord blood cells from more than a month to a few weeks.

Australian scientist and study co-author Paul Simmons, Ph.D., executive vice president for research at Mesoblast, led the research team that originally identified mesenchymal precursor cells and discovered a way to extract mesenchymal cells from the bone marrow for use in other settings.

Only about 25 percent of those needing a blood stem cell transplant have a matching donor — the ideal situation for a transplant. Double-cord blood transplant is one of the main options for the rest, which includes a higher proportion of those with African, Asian or Latino heritage, who are underrepresented among blood stem cell donors.

Patients who receive peripheral blood from a matched donor, the main method used in blood stem cell transplants, on average have their infection-fighting white blood cells (neutrophils) engraft in 11 days and their platelets in 13 days. For a double-cord blood transplant, the same cells engraft in 26 days and 53 days, respectively.

“That isn’t good enough,” Shpall said, who also directs MD Anderson’s Cord Blood Bank . She and other researchers have long sought optimal ways to expand cord blood. The key cells are blood stem cells, which can differentiate into any type blood cell — platelets, white cells or red cells.

Expansion hastens white cell, platelet engraftment

In 31 high-risk patients, the team expanded blood cells from one of the two cords transplanted. They compared outcomes to 80 cases of standard double-cord blood transplant reported to the Center for International Blood and Marrow Transplantation.

The study’s composite endpoint of neutrophil engraftment within 26 days, platelet engraftment within 60 days and survival at 100 days was reached by 63 percent of the expanded cord blood group compared with 24 percent among controls.

Patients with expanded cord blood had:

* Median time to neutrophil engraftment of 15 days, compared to 24 for controls.

* Median time of platelet engraftment of 42 days, compared with 49 for controls.

* Cumulative neutrophil engraftment rate of 88 percent at 26 days, compared with 53 percent in control cases.

* Cumulative platelet engraftment rate of 71 percent at 60 days, compared with 31 percent in controls.

“In addition to the faster engraftment of neutrophils and platelets, the quality of engraftment was better than anything we’ve seen,” said first author Marcos de Lima, M.D., who led the study while on MD Anderson’s faculty and is now professor of medicine at Case Western Reserve University School of Medicine in Cleveland and Section Chief, Hematologic Malignancies and Bone Marrow Transplantation, University Hospitals Case Medical Center Seidman Cancer Center.

Goals: Less bleeding, fewer infections, hospital stays and transfusions

Cord blood transplant patients often need platelet transfusions for months,” de Lima said. “Most of the control group did not start making their own platelets, while in the study group, 70 percent of patients engrafted within 60 days.”

“From patients’ perspective, these are things you want to see going forward: less bleeding, less infection, fewer trips to hospital and less dependence on transfusions,” de Lima said.

Mesoblast is sponsoring a prospective, randomized Phase 3 trial led by Shpall in 15 centers that will compare 120 patients who receive one expanded and one regular cord blood transplant to 120 others who get the standard double cord transplant.

Recreating bone marrow environment in lab flasks

Shpall and Ian McNiece, Ph.D., also a professor in Stem Cell Transplantation and Cellular Therapy, have been working on cord blood expansion for 15 years. They thought mesenchymal precursor cells, which form a supportive network in the bone marrow that allows blood cells to grow, would enhance cord blood cell expansion. The stromal cells do not provoke an immune response when donated.

They developed a technique to take mesenchymal stromal cells from a relative of the patient, cultivate those cells, and then expand cord blood on a layer of the cells in the lab. The logistics and time involved in this procedure limited enrollment in the clinical trial. They evaluated Mesoblast’s cells, found them to be superior to donor cells in terms of expansion of blood-forming precursors, and switched to the off-the-shelf cells.

“This really recapitulates what happens in our bone marrow, where mesenchymal stromal cells provide the optimal environment for blood stem cells to proliferate and differentiate,” McNiece said. “We also supplement growth factors to the media the cells are grown in to drive them in a direction of differentiation we think is optimal for patient treatment.”

Source: Science News, University of Texas M.D. Anderson Cancer Center


Five big strides to fight lung disease in our tiniest patients

230px-CXR_-_Bronchopulmonary_dysplasia For Ottawa scientist and neonatologist Dr. Bernard Thébaud, even a major paper that answers five significant questions still doesn’t seem quite enough in his determined path to get his laboratory breakthrough into the neonatal intensive care unit (NICU). Dr. Thébaud’s proposed therapy would use stem cells from umbilical cords to treat a disease previously thought to be untreatable—bronchopulmonary dysplasia, or BPD.

“BPD is a lung disease described 45 years ago in which we have made zero progress. And now, with these cord-derived stem cells there is a true potential for a major breakthrough,” says Dr. Thébaud, a senior scientist at the Ottawa Hospital Research Institute and CHEO Research Institute, a neonatologist at CHEO and The Ottawa Hospital, and a professor in the Faculty of Medicine at the University of Ottawa.

“I am confident that we have the talent and the tools here at CHEO and OHRI to find a treatment for BPD. These findings published today are helping us get there,” continues Thébaud.

BPD affects approximately 10,000 very premature newborns in Canada and the U.S. every year. The lungs of these infants are not developed enough to sustain them, so they must receive oxygen through a breathing machine. However, this combination of mechanical ventilation and oxygen damages the lungs and stops their development. In addition, longer stays in the NICU for these extremely premature babies affect the normal development of other parts of the body, including the retina, the kidneys and the brain.
Today in the journal Thorax, Dr. Thébaud’s team provides significant findings in experiments with newborn rats given oxygen. The lung development of a newborn rat mimics that of a premature baby born at 24 weeks. The five major findings reported in Thorax are:

1. Stem cells called mesenchymal stromal cells (MSCs) from a human umbilical cord (not the blood) have a protective effect on the lungs when injected into the lungs as they were put on oxygen.

2. MSCs had a reparative effect when injected two weeks after being on oxygen.

3. When conditioned media—a cell-free substance produced by MSCs—was administered instead of MSCs, it was found to have the same protective and reparative effects as the stem cells.

4. When examined after six months (the equivalent of 40 human years), treated animals had better exercise performance and persistent benefit in lung structure.

5. MSCs did not adversely affect the long-term health of normal rats. One of the concerns about stem cells is that by promoting cell growth, they may cause cancerous growth. To address this question, Dr. Thébaud gave MSCs to a control group that was not treated with oxygen. When examined after six months, these animals were normal and healthy.

Within two years, Dr. Thébaud wants to be talking about a pilot study with 20 human patients showing that this stem-cell therapy is feasible and safe, and in four years he wants to embark on a randomized control trial. These are all steps in his profound desire to help the babies he sees in the NICU with BPD, and he is confident a treatment will be developed.

Source: medicalxpress.com