Stem cells may enhance capability of heart cells to regenerate
By Corydon Ireland

Harvard News Office

During a fatal heart attack, at least 1 billion heart cells are killed in the left ventricle, one of the heart’s two big lower pumping chambers that move blood into the body.

In less severe coronaries, dead cardiac cells are replaced by connective tissue cells that form scar tissue in the damaged heart. But the result is never very satisfactory. Scarred ventricular walls are thin, and don’t contract very well — a problem in a workhorse organ designed for sustained pumping.

Inadequate heart repair concerns British-trained developmental biologist Christine Mummery, who has made cardiac cells her specialty. She’s the Harvard Stem Cell Institute Radcliffe Fellow, and will be in residence at Harvard for a semester. (Most Radcliffe Fellows — who number about 50 a year — stay through May.)

Mummery is group leader at the Hubrecht Laboratory of the Netherlands Institute for Developmental Biology, and a specialist in converting stems cells to heart and vascular cells that act like new ones. Heart cells, Mummery believes, have an untapped regenerative capacity that can be enhanced by transplanting stem cells that grow into efficient heart muscle.

Mummery is interested in using laboratory heart cells as a model for cardiac activity — which someday might help scientists identify novel genes, or screen new drugs inexpensively.

To explain her ideas last week (Sept. 26), Mummery led about 100 listeners through the ABCs of stem cell research. The lecture, in a crowded second-floor colloquium room at 34 Concord Ave., near Radcliffe Yard, was the second in a series of public talks by 2007-08 Radcliffe Fellows.

“I’m going to tell you about stem cells, warts and all,” said Mummery. She also hoped that some scientific grounding in the issue would give her lay audience critical perspective on promising therapies — including medical “breakthroughs” that are nothing of the kind.

A lot of conditions are already popularly associated with stem cell therapy, including Parkinson’s disease and diabetes, said Mummery. But many of them don’t belong in that arena, she said, because too many cells or kinds of cells are affected. Among the conditions unlikely to be mitigated by stem cell therapies are Alzheimer’s, stroke, and multiple sclerosis (MS).

Stem cells are different from other cells in the human body because they can change — “differentiate” — into other cell types. This variability makes stem cells exciting, since they could in theory replace damaged or defective cells.

There are two basic types, explained Mummery, whose Radcliffe talk was illustrated with slides of pictures, graphs, and text.

Adult stem cells, from bone marrow and elsewhere, do not present ethical problems. They can be used — though with difficulty — in conditions affecting the skin, hair, pancreas, bone, and perhaps the brain and heart. But there are too few adult stem cells to do much good, she said. They also change unreliably, and only into a limited number of other cell types.

On the other hand, embryonic stem cells “are ethically very sensitive,” said Mummery, because the embryo has to be destroyed to harvest them. But these versatile cells can transform into all of the human body’s 200 cell types.

Adult stem cells are close to being used in human clinical applications for brittle (unstable) diabetes, for making bone and cartilage, and for skin cell transplantation. But for heart disease, so far, adult stem cells have been a bust.

Skeletal muscle stem cells transplanted into the heart sometimes cause cardiac rhythms to go haywire. And injecting bone marrow cells into the heart carries the risk of creating bone matter there. After four clinical trials on humans, said Mummery, “we haven’t solved the problem of where we’re going to get contractile heart cells from.”

Cord blood — blood that remains in the umbilical cord and placenta after birth — is talked about in the press as a source of embryonic-like blood cells, said Mummery. For a price, some European firms will even store cord blood in hopes of medical advances.

But there is never enough to “treat more than a child,” said a skeptical Mummery. Cord blood — likely storable for up to 15 years — is also impractical for adult conditions, like heart disease, which occur much later in life. Still, bogus stem cell “treatments” are still out there, said Mummery — for MS (in Turkey, using untested cord blood) and amyotrophic lateral sclerosis (in China, using fetal olfactory neurons).

In the Netherlands, Mummery has induced heart attacks in mice, then injected human cardiac cells into the affected area. Grafts developed, and new cells survived for more than six months — “but we still cannot cure a mouse,” said Mummery. “Why? That’s one of the reasons I’m here [at Harvard],” she said.

Twice a week she works with researchers at Massachusetts General Hospital. This month, they’ll start a series of experiments transplanting cells into mouse hearts. They’ll use human adult cardiac progenitor cells, which are undifferentiated and have some capacity for self-renewal. And endothelial cells from the lining of blood vessels, which form pavement-like layers of tissue and are thought to be strongly adaptive.

Mummery will also use her time as a Radcliffe Fellow to work with Kevin Kit Parker, an assistant professor of biomedical engineering at the Harvard School of Engineering and Applied Sciences, where he directs the Disease Biophysics Group.

Their working hypothesis: Cells transplanted to the heart do not exact enough force, and may be too isolated to be effective. Mummery and Parker will investigate how the shape of a transplanted heart cell affects its electrical properties — and therefore the relative force of heart contraction.

“The idea is to exchange materials and ideas,” said Mummery of her dual experiments while at Harvard. She’ll visit again in the spring.

http://www.news.harvard.edu/gazette/...9-mummery.html

Stemcell patient believes he'll walk again
12:00a.m. 6 October 2007
| By Amy Remeikis

For the first time in two years Andrew McGinty’s feet respond to tickling.

The slight downward movement of his toes, which most of us take for granted, is a cause for celebration for the Palmwoods dad and his family.

And it has given him hope that he will walk again.

The 41-year-old has just returned from two-and-a-half months in India, where he underwent stem cell therapy at the Delhi Nu-tech Medicare facility, run by Dr Geeta Shroff.

He learnt about the clinic after seeing Sonya Smith, a Brisbane woman he met in hospital after they were both first paralysed, give a television interview on her return from her first round of treatment claiming she had sensations in her lower body.

Andrew’s spinal cord was damaged between his T6 and T7 vertebrae after a motorcycle accident in Caloundra in October 2005.

After contacting Dr Shroff and speaking with other patients, Andrew and his family made the decision to put their life on hold in June and go to a country they knew next to nothing about in the hopes the former concreter would regain some feeling.

Now, a fitter, more relaxed Andrew is sitting in his Palmwoods home, demonstrating his toes moving.

“I couldn’t do that before,” he said, while his partner of nine years, Sarah-Jayne Matthews runs her nails down the soles of his feet, causing his toes to curl downwards.

“Sarah could run her fingers up and down my feet all day and there would be no response.

“I don’t have the feeling yet, but they are a lot more sensitive.

“And now the ball has started rolling, I’m going to keep it rolling.”

Andrew underwent a series of injections and intense physiotherapy during the two-and-a-half months he spent in India.

He was one of several patients, including six Australians, receiving the treatment, for a series of conditions including blindness, motor neurone disease, Parkinson’s Disease and other spinal injuries.

While he admits that his improvements were not as big as he was hoping for, he has more sensation in his lower limbs, his nerve pain has become more manageable and his bladder has strengthened.

“You don’t know what’ll happen, but in my mind, after the improvements I’ve had I know it is working,” he said.

“I have more good days now, then bad. Some days the nerve pain was so bad and for me, the only thing I found that alleviated it was lying down. Now I am up until 6-7 o’clock at night. I feel happier.

“And with my bladder now, my body is doing most of the work.

“My body is identifying when my bladder is getting full, so it is passing the urine. I haven’t had that since the accident.”

He said he also has more strength in his trunk and to some extent, can also crawl, which he said he couldn’t have done before the treatment.

“They are straight up with you. They tell you it is going to take time. You can’t go there expecting miracles, or a quick fix. So you can’t expect too much. It comes down to your injury and how much damage you have done. It takes time for the body to heal, for the stem cells to regenerate.

“I believe in this procedure. After what I saw with my own eyes over there, I mean I saw people with lower breaks (those with spinal injuries further down their body) move their legs under their own steam. I saw that. I saw them when they came in and couldn’t move to having treatment and moving their legs up.”

The family are hoping to save enough money to buy a physio-table to help with Andrew’s on-going physiotherapy so he can retain the muscle strength he has built ahead of his second treatment planned for next year.

He hopes to be able to return to India for the second round, which lasts for two to three weeks.

“I’m going to work to keep my body in as good as condition as I can so I am in good physical state for the next round.

“It is hard to explain to people who aren’t in my position, but I know I have improved. It’s given me hope. I know, that one day I will walk again.

In the mean time, he is hoping the Australian government will change its attitude to stem cell therapy.

“Imagine if Johnny Howard or one of his family members ended up in a wheelchair. I bet we’d be looking at having the procedure here then.

“They have closed their eyes and ears to it and they are not even considering it. But I know it helps. It is something they really need to look into, because there are so many people it could be helping. I know. I have seen it.”

http://www.thedaily.com.au/news/2007...ll-walk-again/