Brittle-Bone Babies Helped by Fetal Stem Cell Grafts

Dec. 16, 2013 Osteogeneis imperfecta (OI) is a congenital bone disease that causes stunted growth and repeated, painful fracturing. Ultrasound scans can reveal fractures already in the fetus, and now an international team of researchers from Sweden, Singapore and Taiwan have treated two babies in utero by injecting bone-forming stem cells. The longitudinal results of the treatment are published in the journal Stem Cells Translational Medicine. The babies were treated withmesenchymal stem cells, connective tissue cells that can form and improve bone tissue. The stem cells were extracted from the livers of donors and although they were completely unmatched genetically, there was no rejection and the transplanted cells were accepted as self. Back in 2005, a paper was published from Karolinska Institutet in Sweden describing how stem cells were given to a female fetus. The present study describes how the girl suffered a large number of fractures and developed scoliosis up to the age of eight, whereupon the researchers decided to give her a fresh stem cell graft from the same donor. For the next two years the girl suffered no new fractures and improved her growth rate. Today she takes dance lessons and participates more in PE at school. Another unborn baby with OI, a girl from Taiwan, was also givenstem cell transplantation by the Karolinska Institutet team and their colleagues from Singapore. The girl subsequently followed a normal and fracture-free growth trajectory until the age of one, when it levelled off. She was given a fresh stem cell treatment and her growth

resumed. The girl started to walk and has since not suffered any new fractures. Today she is four years old. "We believe that the stem cells have helped to relieve the disease since none of the children broke bones for a period following the grafts, and both increased their growth rate," says study leader Dr Cecilia Gtherstrm, researcher at Karolinska Institutet's Department of Clinical Sciences, Intervention and Technology. "Today, the children are doing much better than if the transplantations had not been given. OI is a very rare disease and lacks effective treatment, and a combined international effort is needed to examine whether stem cell grafts can alleviate the disease." The researchers have also identified a patient, a boy from Canada, who was born with OI caused by exactly the same mutation as the Swedish girl had. The boy was not given stemcell therapy and was born with severe and widespread bone damage, including numerous fractures and kyphosis of the thoracic vertebrae, which causes such overcurvature of the spine that it impairs breathing. The boy died of pneumonia within his first 5 months. Journal Reference: 1. Cecilia Gtherstrm, Magnus Westgren, S W Steven Shaw, Eva strm, Arijit Biswas, Peter H Byers, Citra N Z Mattar, Gail E Graham, Jahan Taslimi, Uwe Ewald, Nicholas M Fisk, Allen E J Yeoh, Ju-Li Lin, Po-Jen Cheng, Mahesh Choolani, Katarina Le Blanc and Jerry K Y Chan. Pre and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience. Stem Cells Translational Medicine, December 2013

Fetal stem cell grafts successfully help brittle-bone babies Marie Ellis
In an international collaboration, researchers from Sweden, Singapore and Taiwan successfully treated two babies with a congenital bone disease that causes stunted growth and repeated fracturing by injecting them in utero with bone-forming stem cells. Results of their longitudinal study have been published in the journal Stem Cells Translational Medicine. Osteogenesis imperfecta (OI) not only stunts the growth of those who suffer from this disease, but the repeated fracturesit causes are painful. However, this condition can be recognized prenatally with anultrasound, so researchers from the Karolinska Institutet in Sweden published a paper in 2005 detailing how mesenchymal stem cells - connective tissue cells that form and improve bone tissue - were given to a female fetus in Sweden. These stem cells were taken from the livers of donors, and the researchers note that though the donors and recipients were not genetically matched, there was no rejection. In this recent study, the team explains how the girl experienced several fractures and had scoliosis by age 8. At this point, the researchers gave her a fresh stem cell graft from the same donor as before. For the following 2 years, the child did not experience any new fractures and her growth rate improved. Today, the researchers say, she participates in dance lessons and gym class at school.

'Internationaleffortneeded'forthisraredisease The team from Karolinska Institutet, along with colleagues in Singapore, detail how they gave another baby girl from Taiwan - who was shown prenatally to have OI - stem cell transplantation in utero.

The girl experienced a normal, fracture-free rate of growth until she was 1-year-old, at which point the team gave her a fresh stem cell treatment.

Her normal growth resumed, the team says, and now, at the age of 4, she is able to walk normally and has not experienced any new fractures. "We believe that the stem cells have helped to relieve the disease since none of the children broke bones for a period following the grafts, and both increased their growth rate," says study leader Dr. Cecilia Gtherstrm, from Karolinska Institutet.

She adds: "Today, the children are doing much better than if the transplantations had not been given. OI is a very rare disease and lacks effective treatment, and a combined international effort is needed to examine whether stem cell grafts can alleviate the disease." Furtherstudiesrequired The team says they identified a male patient from Canada who was born with OI, which was caused by the exact same mutation that the girl from Sweden had.

Born with severe widespread bone damage, this boy was not given stem cell therapy like the girls were, and he experienced numerous fractures and kyphosis of the thoracic vertebrae - a condition that causes an extreme curvature of the spine, impairing breathing.

The untreated boy died within his first 5 months from pneumonia, the investigators say. Although the researchers say their findings suggest the stem cell therapy treatment "appears safe and is of likely clinical benefit," they add that "the limited experience to date means that it is not possible to be conclusive and that further studies are required."

I. II. III.

Summary Reaction Recommendation