Philadelphia, Pa. — Adult human stem cells taken from bone marrow have been induced to develop into a wide range of normal tissues, including bone, cartilage, fat, tendon and muscle, when transplanted into fetal sheep. The transplanted human cells have persisted in various sheep tissues for over one year without rejection by the sheep’s immune system. The study offers promise that in the future these cells may be useful for tissue repair or regeneration and for treatment of degenerative diseases such as muscular dystrophy.
"Although a great deal of work remains to be done, these results suggest great potential for the use of these cells in repair of damaged or degenerating tissues, or for generation of new tissues, a process called tissue engineering," said Alan W. Flake, M.D., director of The Children’s Institute for Surgical Science at The Children’s Hospital of Philadelphia, who led the study reported in the November issue of Nature Medicine. "One possible future application might be the transplantation of normal stem cells into a fetus diagnosed with muscular dystrophy. "These cells could then act as a normal stem cell ‘reservoir’ and replace the abnormal muscle with normal muscle as it degenerates over time."
Stem cells are immature cells that develop into specialized cells throughout the body, and those taken from embryos have the broadest potential for giving rise to all the body’s tissues. However, recent studies have shown that cells with broad stem cell potential can be found in various adult tissues as well, including the bone marrow and nervous system.
In the study at Children’s Hospital, researchers harvested mesenchymal stem cells (MSCs) from adult bone marrow. "The transplanted cells developed in a site-specific fashion," said Dr. Flake. "They migrated to different parts of the sheep’s body and differentiated into types of tissue present at each site."
Because the transplanted cells carried human DNA, it was possible to identify them in different tissue. They became cells in skeletal muscle, heart muscle, bone, cartilage, the thymus gland and stroma, which is supporting structure for bone marrow. Furthermore, transplanted human MSCs were found at the site of clipped tails in the sheep, suggesting that those cells were involved in wound healing.
MSC transplants may have a future role in enhancing wound healing after an injury or surgery. Additionally, said Dr. Flake, because MSCs also develop into supporting cells in bone marrow, they might provide a more favorable environment for the transplanted cells used in bone marrow transplants for leukemias and other blood-based diseases. MSCs might also be used in gene therapy, acting as vehicles to deliver beneficial genes to targeted tissues.
Although many institutions are currently investigating various types of stem cells, this is the first study examining transplantation of human MSCs in the fetal sheep model. In this current study, human MSCs were transplanted into fetal sheep early in gestation, at either 65 days or 85 days, before and after the brief window of time when their immune systems mature and become active.
One surprise of the study, according to Dr. Flake, is the persistence of these transplanted cells even in animals that were capable of rejecting foreign cells at the time of transplantation. "This suggests that these cells may have special immunologic properties that may allow transplantation between individuals or even between species without rejection or the need for toxic immunosuppressive drugs," added Dr. Flake.
Collaborating with Dr. Flake in the study was Kenneth W. Liechty, M.D., of Children’s Hospital. Other co-authors were from Children’s Hospital and from Osiris Therapeutics of Baltimore, Maryland, a biotechnology company.
Founded in 1855 as the nation’s first pediatric hospital, The Children’s Hospital of Philadelphia is recognized today as one of the leading treatment and research facilities in the world. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children’s Hospital has fostered discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique outreach and public service programs have brought the 381-bed hospital recognition as a leading advocate for children from before birth through age 19.
Journal
Nature Medicine