Highlights of Stem Cell Research
Due to copyright restrictions, the full text of articles linked below is available only to the NIH community. Those outside the NIH community can access citations and abstracts.
Other Years
2009 Articles
-
Human Corneal Stem Cells Repair Defective Corneas in Mice
The cornea helps to protect the eye from environmental irritants and serves as the eye's outermost lens, contributing between 65—75 percent of the eye's total focusing power. In most cases, scratches on the cornea caused by irritants or trauma can be repaired by the cornea's own stem cells. However, deeper scratches can cause corneal scarring, resulting in a haze on the cornea that can greatly impair vision. In this case, the cornea is unable to repair itself, and a corneal transplant may be needed. As with most transplant organs, corneas are in low supply. NIH-supported scientists transplanted stem cells from the adult human corneal stroma (cells that make up the transparent cornea) into the eyes of mice that exhibit corneal cloudiness. These mice's eyes lack the ability to produce a protein called lumican, which organizes the cornea's collagen in order to make it transparent. After injection of the human cornea stromal stem cells, the transparency of the treated corneas was comparable to those in mice with normal corneas. Treated mice did not reject the transplanted human cells. The scientists will now try to reproduce this result in animals with cornea scarring. If successful, the scientists may be able to develop a potential stem cell therapy for cornea scarring in humans. Stem Cells epub 2009, laboratory of J. Funderburgh.
-
Another Safety Improvement for Generating Induced Pluripotent Stem Cells (iPSCs)
Scientists funded by the Juvenile Diabetes Research Foundation, the United Kingdom, and Canada reprogrammed mouse and human fibroblasts without using potentially dangerous viruses. For both types of fibroblasts, the reprogramming genes and an inducible transcription factor (can be used to turn expression on and off) were carried into the cells by naked DNA sequences. The naked DNA carriers also contained marking sequences that are targeted and "cut out" by specific enzymes. Using these special carriers, the scientists were able to insert reprogramming genes, turn them on for a specific period of time, and then remove the reprogramming genes and the transcription factor by adding the specific enzyme that zeroes in on and cuts out its targets. This method has several benefits: temporary expression of the reprogramming genes, the ability to remove inserted DNA after reprogramming is accomplished, use of a single carrier for all four reprogramming genes, and carriers' seeming increased resistantance to "silencing," or being inactivated (which could explain the higher efficiency as compared to other non-viral carriers).
This method has some potential drawbacks. Insertion of the reprogramming factors is random and could still temporarily interfere with an important gene. Part of the carrier DNA is often left behind even after removal. The DNA cuts made at the DNA removal site are not always repaired correctly. The PiggyBac method used for some of the experiments employs a transposon, or "jumping gene." Jumping genes are known to cause human diseases such as muscular dystrophy or hemophilia, as well as increase susceptibility to cancer. The bottom line: These methods are another step toward improving our ability to reprogram cells and increasing our understanding of reprogramming. However, these methods could still pose a danger to human health if derivatives of these cells are used to treat humans. The cells generated by this method are a valuable research tool and provide useful means to screen drugs and establish human disease models in culture. Nature advance online publication, laboratory of A. Nagy; Nature advance online publication, laboratory of K. Woltjen. 2009 Mar 6.
- Induced Pluripotent Stem Cell–Derived Working Heart Muscle Cells
Heart transplants are done as a life-saving measure for end-stage heart failure when medical treatment and less drastic surgery have failed. Fortunately, most heart transplant recipients (about 90 percent) can come close to resuming their normal daily activities; however, donor hearts are in short supply. NIH-supported scientists have been able to grow heart muscle cells (cardiomyocytes) from induced pluripotent stem cells (iPSCs). They compared cardiomyocytes derived from iPSCs with cardiomyocytes derived from human embryonic stem cells (hESCs). All cardiomyocytes in the study were derived using an embryoid body (EB) method. Both iPSC- and hESC-derived cardiomyocytes showed a reduction in gene expression for OCT4 and NANOG (known to regulate pluripotency) as they differentiated. However, pluripotency gene expression was more variable in iPSC-derived cardiomyocytes. Both types of cardiomyocytes demonstrated heart muscle–specific characteristics, such as organized bands of contraction proteins, and electrical activity that causes them to spontaneously contract. Overall, the iPSC-derived cardiomyocytes are very similar to hESC-derived cardiomyocytes. Due to the short supply of donor hearts for transplantation, these iPSC-derived cardiomyocytes may one day provide an important treatment for the substantial number of people with heart disease. By reprogramming their own skin cells into cardiomyocytes for repairing their heart muscle, patients can avoid the immune-suppressing drugs that accompany traditional heart transplant. Scientists also hope that the derived cardiomyocytes will be useful for testing potential drugs and for understanding the underlying cause of heart disease. Circulation Research advance online publication, laboratory of T. Kamp. 2009 Feb 12.