Stem Cell Report – Summer 2002

Date: 07/02/2002

Adult Skin Cells Reprogrammed Without Cloning

A team of scientists from Norway has succeeded in coaxing one type of adult cell to start behaving like a completely different type of adult cell. The scientists have made human skin cells in a test tube behave as if they were immune system cells, by bathing the skin cells in extracts of the immune cells. In other work, they have been able to get skin cells to behave as if they were nerve cells.

“We can take a skin cell from your body and turn it directly into a cell type that you need to treat a particular disease,” said Dr. Philippe Collas, the leader of the team, whose work was published 5/1/02 in the respected journal Nature Biotechnology.

The technique being developed would allow skin cells from a patient to be turned directly into other types of cells without having to revert first to an embryonic state and without needing women’s eggs. They told Reuters, “That’s the beauty of our system — we are not working with embryos or dealing with stem cells at all. You get around all these issues.” “It would be a one-day procedure, in principal. The patient would come in and give a skin biopsy to the lab to reprogram and the day after you could put the cells back into the patient.” The technique would have immediate applications in cancer. The group is also looking at making insulin-secreting pancreatic cells.

The approach will aid investigation of the mechanisms by which adult stem cells revert to cells capable of differentiating into other types of cells with potential use in therapies for conditions like diabetes, Parkinson’s disease, and heart disease. From a clinical perspective, approaches based on this technology would allow replacement cells to be generated that are compatible with a patient’s immune system, without the ethical problems of generating or destroying embryos.1

Adult Liver Stem Cells Make Pancreatic Cells, Reverse Hyperglycemia in Diabetic Mice

Researchers at the University of Florida have transformed highly purified adult liver stem cells into pancreatic cells. The cells self-assemble in culture to form 3-dimensional islet structures, express pancreatic genes, produce pancreatic hormones, and secrete insulin. When implanted into diabetic mice, the transformed cells reversed their hyperglycemia in 10 days. Dr. Ammon Peck, one of the team leaders, said “Adult stem cells appear to offer great promise for the production of an almost unlimited supply of insulin-producing cells and islets of Langerhans… The ability to grow insulin-producing cells from liver stem cells shows the remarkable potential of adult stem cells for future cell therapy.”2

Adult Bone Marrow Stem Cells Transformed Into Functional Liver Cells

Dr. Catherine Verfaillie’s group at Minnesota continues to show more and more uses for the multipotent adult progenitor cells (MAPC) from bone marrow. The team has now shown that these adult stem cells can transform into functional liver cells. The adult stem cells also were grown in culture for over 100 generations, twice the length of time previously thought possible with adult cells.3

Adult Bone Marrow Stem Cells Can Form Blood Vessels

Scientists at the University of Florida have shown that bone marrow stem cells can form blood vessels in organs very distant from the marrow. Mice received transplants of purified, genetically-engineered bone marrow stem cells, which glowed green. The scientists could track the origin of new blood vessels in the retina of the animals because the new vessels glowed green. “We were able to show that, essentially, the majority of the vessels being repaired in the eye were green,” said Edward Scott, one of the researchers. In some experiments a single adult stem cell was transplanted. “Everything that glowed green in those animals, therefore, came from a single cell,” Scott said. “That was our formal proof that it was indeed a blood stem cell that was making these blood vessels.” The findings have implications for diseases such as diabetes, cancer, heart disease, sight-robbing retinal disorders and a multitude of other medical conditions. “We’re hoping we’ll someday learn how to get your own stem cells to respond on their own and repair vascular damage, whether it’s caused by a heart attack or the circulatory problems associated with diabetes,” Scott said.4

 

Adult Muscle Stem Cells Form Multiple Tissues; Regenerate Dystrophic Muscle

Scientists at the University of Pittsburgh and in Germany have isolated adult muscle stem cells that can grow for long periods in culture, and can transform into muscle, neural tissue, and blood vessels. The transformations could be accomplished both in the lab dish as well as in experimental mice, without immune rejection. The cells improved muscle regeneration in mice that are models of muscular dystrophy.5

  1. A.M. Hakelien et al.; “Reprogramming fibroblasts to express T-cell functions using cell extracts;” Nature Biotechnology 20, 460-466; May 2002.
  2. L. Yang et al.; “In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells;” Proceedings of the National Academy of Sciences USA, Online Early Edition; 10.1073/pnas.122210699; June 4, 2002
  3. R. E. Schwartz et al.; “Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells;” J. Clin. Invest. 109,1291–1302; May 2002
  4. M. B. Grant et al.; “Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization;” Nature Medicine 8, 607-612; June 2002.
  5. Z. Qu-Petersen et al.; “Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration”; Journal of Cell Biology (on-line publication) www.jcb.org/cgi/doi/10.1083/jcb.200108150; May 2002.
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