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.
- Reprogrammed Mouse Skin Cells Cure Mouse Sickle Cell Anemia
Individuals with sickle cell anemia inherit a defective hemoglobin gene that causes their red blood cells (RBCs) to assume a sickle shape. The sickled RBCs clump together and block blood flow, causing pain and organ damage. NIH-funded scientists used a published method (see Human Skin Cells Reprogrammed) to reprogram mouse skin cells derived from a mouse carrying the defective hemoglobin gene, producing induced pluripotent stem cells (iPS cells). They then used homologous recombination to repair the defective hemoglobin gene and directed the iPS cells to become blood-forming (hematopoietic) stem cells. Hematopoietic stem cells are found in bone marrow and produce all the blood cells in the body. Finally, the scientists transplanted the repaired hematopoietic stem cells into the bone marrow of sickle cell mice whose own marrow was destroyed in order to eliminate the defective hematopoietic cells. The transplanted cells were able to regenerate the mice's blood systems, including production of normal rather than sickled red blood cells. This research advance demonstrates that reprogrammed adult mouse cells (iPS cells) are capable of producing cells that can treat disease in mice. However, the methods used in this study include use of a cancer-promoting gene and inactivated viruses, and are not likely to be used to treat humans. If scientists can develop safer methods to reprogram adult cells, iPS cells could one day generate cells and tissues to treat human diseases. Science 318:1920–23, laboratory of R. Jaenisch. 2007 Dec 6.
- Human Skin Cells Reprogrammed
In 2006, Japanese scientists were able to reprogram adult mouse skin cells to behave like mouse embryonic stem cells, although the reprogrammed cells could not produce eggs or sperm (gametes). The scientists named the cells iPS cells, for induced pluripotent stem cells. In 2007, the Japanese researchers successfully generated gametes from iPS cells, and their results were verified and extended by another independent laboratory. Now, simultaneous publications from the Japanese scientists and a team of NIH-supported scientists report that they have each succeeded at reprogramming adult human skin cells to behave like human embryonic stem cells (hESCs). The Japanese team forced adult skin cells to express Oct3/4, Sox2, Klf4, and c-Myc, while the NIH-supported team forced adult skin cells to express OCT4, SOX2, NANOG, and LIN28. The genes were all chosen for their known importance in maintaining the so-called "stemness" properties of stem cells. In both reports, the adult skin cells are thus reprogrammed into human iPS cells that demonstrate important characteristics of pluripotency, including the ability to differentiate into cells characteristic of each embryonic germ layer. The techniques reported by these research teams will enable scientists to generate patient-specific and disease-specific human stem cell lines for laboratory study, and to test potential drugs on human cells in culture. However, these human iPS cells are not yet suitable for use in transplantation medicine. The current techniques use viruses that could generate tumors or other undesirable mutations in cells derived from iPS cells. Scientists are now working to accomplish reprogramming in adult human cells without using potentially dangerous viruses. Cell 131:861–72, laboratory of S. Yamanaka, 2007 Nov 30; Science 318:1917–1920, laboratory of J. Thomson, 2007 Dec 21.
- Monkey Embryonic Stem Cells Produced following SCNT
One possible way to produce patient-specific tissues for therapies is to generate them from stem cells produced by somatic cell nuclear transfer, or SCNT. However, the standard protocol for SCNT in other species has not been successful in primates, such as monkeys and humans. Now scientists using a modified SCNT protocol have successfully generated stem cell lines from rhesus macaque embryos (see the NIH Research Matters article Embryonic Stem Cell Milestone Achieved in Primates). The scientists eliminated the use of a stain (Hoechst) to visualize the egg's chromosomes, opting instead to use a specialized imaging system that enables visualization of the chromosomes without use of a stain. The scientists also removed calcium and magnesium from the medium bathing the eggs, in an attempt to keep the eggs from spontaneously "activating," or releasing internal stores of calcium ions. The monkey embryonic stem cells thus produced demonstrated key characteristics of pluripotency, including the ability to form tissues from all of the embryonic germ layers. Since monkeys are close to humans in evolution, scientists may be able to study these monkey stem cells and learn how to generate similar cells in humans. Nature 450:497–502, laboratory of S.M. Mitalipov. 2007 Nov 22.
- Heart Cells Derived from Human Embryonic Stem Cells Help Restore Rat Heart Function
Heart disease impairs the heart's ability to pump blood and sustain the body's organs and tissues. Scientists hope to one day repair or replace damaged heart muscle cells with stem cells, but they face many critical challenges. These include generating enough new heart cells, making sure transplanted heart cells are not contaminated with immature or other cell types, and ensuring the heart cells' survival after transplantation. NIH-funded investigators developed a new technique to generate large numbers of pure cardiomyocytes (heart muscle cells) from human embryonic stem cells (hESCs). They also formulated a "prosurvival" cocktail (PSC) of factors designed to overcome several known causes of transplanted cell death. The scientists then induced heart attacks in rats and injected the rat hearts with either hESC-derived human cardiomyocytes plus PSC (treatment group) or one of several control preparations. Four weeks later, the scientists identified human cardiomyocytes being supported by rat blood vessels in treated rat hearts. The treated rat hearts also demonstrated an improved ability to pump blood. The scientists did not identify any surviving human cells in the control animals, and they saw no improvement in heart function. This work demonstrates that hESC-derived cardiomyocytes can survive and improve function in damaged rat hearts. Scientists now hope to learn how the human cells improved the rat hearts, and eventually to test this method to treat human heart disease. Nature Biotechnology 25(9):1015–1024, laboratory of CE Murry. 2007 Sept.
- Researchers Isolate Adult Stem Cells for First Time in Tendon
This research advance was featured in a press release from the National Institute of Dental and Craniofacial Research (NIDCR). Nature Medicine (10):1219–27, laboratory of M. Young. 2007 Oct.
- Scientists Uncover the Origin of the Korean Stem Cell Line SCNT-hES1
In 2004, scientists led by Woo-Suk Hwang at the Seoul National University in South Korea reported that they had succeeded in using somatic cell nuclear transfer (SCNT) to establish a human embryonic stem cell (hESC) line (see original report here). They claimed to have combined the DNA of a woman's mature cell with her donated egg (nucleus removed) and stimulated the newly combined cell to divide. They named their new hESC line SCNT-hES1. In January 2006, the editors of the journal Science retracted this and a subsequent paper from the Hwang research laboratory, citing Seoul National University's investigative report (PDF; get Adobe Reader), which determined that "a significant amount of the data presented in both papers is fabricated." A multinational group of NIH-funded investigators developed extensive experience identifying the origin of stem cell lines based upon their patterns of genetic recombination. Recently, this group examined the genetic recombination patterns of SCNT-hES1 and determined that it was likely derived via parthenogenesis instead of SCNT. The authors speculate that the Hwang lab's cell line was the result of unsuccessful enucleation (removal of the nucleus), or that it fused with its own polar body after enucleation. Cell Stem Cell doi:10,1016/j.stem.2007.07.001 (PDF; get Adobe Reader), laboratory of G.Q. Daley. 2007 Sep.
- Human Embryonic Stem Cells (hESC) Prefer to Become Different Types of Neurons
Possible successful treatment for individuals with neurodegenerative diseases may be achieved by adequately replacing their damaged or missing nerve cells with new nerve cells created from human embryonic stem cells (hESCs). Scientists have shown that hESCs can differentiate into nerve, heart, and other cells that can be implanted to restored damaged tissue. However, it has been difficult to determine the correct conditions to grow the hESCs to produce a specific cell type. Now, NIH- and privately supported scientists have compared mature neurons grown from two hESCs on the NIH Stem Cell Registry. They developed procedures to differentiate the two stem cell lines first into neural progenitor cells, and then into mature neurons. The scientists studied the neurons in a new culture technique to observe the biology, genetics, and development of synapses, which are the critical junctions between neurons where much of the signaling and communication occurs. They also compared the genetic microRNAs, small snippets of genetic material that are believed to be significant regulators of stem cell differentiation, produced by the two types of neurons. This study also showed that the two different hESC lines had the tendency to produce different types of neurons. Determining why different hESC lines grow and differentiate differently will help scientists start with any hESC line to produce particular cell types that can be used to help repair or regenerate damaged tissues. Proceedings of the National Academy of Sciences of the USA 104(34):13821–13826, laboratory of Y. Sun. 2007 Aug 21.
- International Stem Cell Initiative Compares Embryonic Stem Cells Throughout the World
The International Stem Cell Initiative (ISCI) was established to compare a large and diverse set of human embryonic stem cell (hESC) lines derived and maintained in different research laboratories throughout the world. The ISCI has published its comparison of 59 hESC lines from 17 individual laboratories. Overall, the lines were remarkably similar. However, the ISCI identified differences in expression of imprinted genes and in X-chromosome inactivation. Nature Biotechnology 25(7):803–16. 2007 Jul.
- Tissue-Matched Human Stem Cells Created without Cloning
Scientists have proposed the use of somatic cell nuclear transfer, or SCNT, to create stem cells that are tissue-matched to an individual. This process is also known as therapeutic cloning. However, due to exchange of genetic information between pairs of like chromosomes (homologous recombination) during the egg's meiosis, the stem cells created using this method may still not be a precise match for the nucleus donor. Previously, scientists derived stem cells from a mouse embryo that was created using a process known as parthenogenesis (see Tissue-Matched Stem cells Created in Mice without Cloning). Parthenogenesis describes an embryo created without fertilization of the egg by a sperm, thus omitting the sperm's genetic contributions. Now, privately funded scientists have used parthenogenesis to derive human embryonic stem cell lines (hESCs). These identified stem cell lines retained the identical "self" (genetic information of the egg donor) and were shown to be pluripotent. These hESC lines were also derived and grown on a human feeder layer. This technique may lead to the ability to generate tissue-matched cells for transplantation to treat women who are willing to provide their own egg cells. This technique could also offer an alternative method for deriving tissue-matched hESCs that do not require destruction of a fertilized embryo. Cloning Stem Cells advance online publication, laboratory of J.D. Janus. 2007 Dec 19.
- Counterparts: Rodent Embryonic Stem Cell and Human Embryonic Stem Cell
Typically, embryonic stem cell (ESC) lines have been derived from the inner cell mass of a blastocyst-stage pre-implanted embryo. However, scientists have now reported that ESC lines can be derived from the epiblast, a derivative of the inner cell mass in an embryo at a later stage of development. It has also been known that rodent ESCs are similar to human ESCs (hESC), but they differ in how they maintain pluripotency, the ability to develop into virtually any cell type in the body. Now, two independent teams of British, U.S., and Swedish scientists supported by the NIH, the British government, and other UK sources have reported these mouse and rat epiblast-derived stem cell (EpiSC) lines are even more similar to hESCs. Unlike mouse ESCs, which require culture conditions different from hESCs to grow, EpiSCs grow better in culture conditions similar to those for hESCs. The EpiSCs also share other molecular characteristics and cell surface markers with hESCs. Because of the similarities between EpiSCs and hESCs, these studies suggest an additional method for creating pluripotent stem cells that may offer a new animal model for understanding how human stem cells grow and differentiate. Nature advance online publication and Nature advance online publication, laboratories of R. McKay and R. Pedersen. 2007 June 27.
- New Therapeutic Cloning Technique Does Not Require Unfertilized Eggs
A new technique developed by NIH-funded scientists at Harvard University may expand scientists' options when trying to "reprogram" an adult cell's DNA. Previously, successful somatic cell nuclear transfers (SCNT, or cloning) relied upon the use of an unfertilized egg. Now, the Harvard scientists have demonstrated that by using a drug to stop cell division in a fertilized mouse egg (zygote) at mitosis, they can successfully reprogram an adult mouse skin cell by taking advantage of the "reprogramming factors" that are active in the zygote at mitosis. They removed the chromosomes from the single-celled zygote's nucleus and replaced them with the adult donor cell's chromosomes. The active reprogramming factors turned genes on and off in the adult donor chromosomes, to make them behave like the chromosomes of a normally fertilized zygote. After the zygote was stimulated to divide, the cloned mouse embryo developed to the blastocyst stage, and the scientists were able to harvest embryonic stem cells from it. When the scientists applied their new method to abnormal mouse zygotes, they succeeded at reprogramming adult mouse skin cells and harvesting stem cells. If this technique can be repeated with abnormal human zygotes created in excess after in vitro fertilization (IVF) procedures, scientists could use them for research instead of discarding them as medical waste. Human embryonic stem cells generated in this way would be a genetic match for the chromosome donor (see therapeutic cloning), helping to avoid the problem of transplant rejection. In addition, use of excess IVF zygotes for SCNT would eliminate the need for human egg donations. This technique may overcome some ethical objections to deriving stem cells from 5-day-old human embryos, since the abnormal zygotes that would be used for this technique are not believed capable of surviving until birth. Nature 447:679–686, laboratory of K. Eggan. 2007 Jun 7.
- New Advances in Reprogramming Adult Mouse Cells
In 2006, Japanese scientists reported that they could use a virus to introduce four important stem cell factors into adult mouse cells and reprogram them to behave like embryonic stem (ES) cells (see Scientists Reprogram Adult Mouse Skin Cells by Adding Defined Factors). They called the reprogrammed cells iPS, for induced pluripotent stem cells. However, iPS produced using the original technique cannot do everything that ES cells can do. Notably, the original iPS cells do not make sperm and egg cells when injected into an early mouse blastocyst, and they do not make some changes to their DNA that help silence genes. Now the same scientists have modified their original technique, and they report that they can select for iPS that can make sperm and eggs. Their report is accompanied by another from an NIH-funded laboratory, which successfully reproduced the Japanese group's results. In addition, the NIH-funded scientists determined that iPS DNA is modified in a manner similar to ES cells, and important stem cell genes are expressed at similar levels. They also demonstrated that iPS injected into an early mouse blastocyst can produce all cell types within the developing embryo, and such embryos can complete gestation and are born alive. These research advances were made in mice, and scientists must still determine if the same techniques can reprogram cells of adult humans. If this can be accomplished, scientists should be able to develop stem cell lines from patients who suffer from genetic diseases, such as Huntington's Disease, spinal muscular atrophy, muscular dystrophy, and thalessemia. Such lines would be invaluable research tools for understanding specific diseases and testing potential drugs to treat them. A second use of reprogrammed cells would be to repair damaged tissues in the human body. The Japanese scientists noted that the virus used to introduce the stem cell factors sometimes caused cancers in the mice. This represents a significant obstacle that must be overcome before the technique can lead to useful treatments for humans. This work suggests an additional method for creating pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help scientists learn how to reprogram cells to repair damaged tissues in the human body. Nature advance online publications, 6 June 2007. Laboratories of R. Jaenisch and S. Yamanaka.
- Scientists Identify Olfactory Stem Cells in Mammals
The odor-detecting tissue lining the nose (olfactory epithelium, or OE) is exposed to a wide variety of environmental insults—dirt, chemicals, other pollutants, viruses, and bacteria. These insults frequently kill cells in the OE—yet most humans can still detect odors. This is possible because the OE can regenerate itself. Although scientists presumed that the regenerative capability was due to division of resident stem cells, there were two possible candidates for the stem cell: globose basal cells (GBCs) or horizontal basal cells (HBCs). Scientists supported by the NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) used a genetic tag to label early mouse HBCs and all of their cellular offspring, or daughter cells. Under normal circumstances the HBCs divided only rarely, and GBCs replaced any lost cells. Yet after severe damage that destroyed even the GBCs, the HBCs divided to produce GBCs—which subsequently produced all cell types in the OE (except HBCs). Scientists can now study how damaged OE stimulates division of its HBC stem cell population. This type of investigation may also help scientists figure out how to "jump start" stem cell division to help repair other organs, such as damaged nerves or insulin-producing cells. Nature Neuroscience 10(6):720–6, laboratory of R.R. Reed. 2007 Jun.
- Mice Regenerate Hair Follicles
This research article was featured in NIH Research Matters, a review of NIH research from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health. Nature 447(17):316–320, laboratory of G. Cotsarelis. 2007 May.
- Human Embryonic Stem Cells Give Rise to Lung Tissue
If scientists treating disease or injury by transplanting cells that were derived from human embryonic stem cells (hESCs) accidentally transplanted some undifferentiated cells, the undifferentiated cells might keep dividing, resulting in a tumor. Thus, before using hESCs to treat humans, scientists must first be able to generate a pure population of a specific cell type. NIH-funded scientists have developed a method to coax hESCs into becoming cells that resemble lung epithelial cells. The scientists engineered a virus (modified to eliminate its disease-transmitting function) to infect cells with two genes simultaneously, one that drives them into becoming a specialized type of lung cell and another that enables them to resist being killed by a drug (neomycin). Only those cells that express the two genes survived when the scientists treated the culture dish with neomycin. In this way, they were able to generate a pure population of lung-like cells, with no contaminating cells. The surviving cells had the appearance and shape of lung-lining cells called alveolar type 2 cells. These cells help maximize air exchange, remove fluid from the lungs, serve as a pool of repair cells, and fight airborne diseases. The hESC-derived alveolar type 2–like cells also made proteins characteristic of that cell type. This research represents an important step toward developing hESCs for use in treating humans. In addition to its usefulness for creating lung cells, this technique may also be used to generate pure populations of other types of desired human cells. Proceedings of the National Academy of Sciences of the USA 104(11):4449–4454, laboratory of R.A. Wetsel. 2007 March.
- Adult Stem Cells Derived from Blood Vessels Can Regenerate into Skeletal Muscle
Blood vessels in skeletal muscle are composed of two cell types, endothelial and perivascular (also known as pericytes, vascular smooth muscle cells, or mural cells). Recently, scientists funded by the Muscular Dystrophy Association (MDA), Italian government, and other sources have discovered that "pericyte-derived" stem cells are located around small blood vessels in muscle tissue and have the potential to regenerate skeletal muscle in individuals with muscular dystrophy. The scientists injected the pericyte-derived cells taken from healthy human muscle tissue into immune-deficient mice missing the dystrophin protein (the cause of human Duchenne muscular dystrophy). The mice showed functional improvement in walking and holding onto a moving rod. Unlike satellite cells in the muscle that can also regenerate skeletal muscle but need to be injected directly into the affected muscle, the new pericyte-derived cells could repair the muscle and reconstitute the muscle cell population by crossing the blood vessel wall into the muscle. Therefore, if these new pericyte-derived stem cells taken from a individual's own muscle could be easily injected into the bloodstream, this would be an ideal treatment for muscular dystrophy. Nature Cell Biology 9(3):255–267, laboratories of G. Cossu and P. Bianco. 2007 March.
- Stem Cells Improve Symptoms of Neurodegenerative Disease
In humans, Sandhoff Disease kills nerve cells (neurons) throughout the body because faulty enzymes cause a toxic buildup of debris inside the neurons. Individuals with the disease usually die by age 3, and there is currently no effective treatment. NIH-funded scientists tested whether stem cells from different sources could improve disease symptoms in a mouse model of human Sandhoff Disease. They transplanted either adult mouse neural stem cells, fetal human neural stem cells, or neural stem cells derived from human embryonic stem cells into brains of mice with the disease. All types of transplanted neural stem cells prolonged the lifespan and delayed loss of motor function in treated mice. However, the number of transplanted cells that replaced dead neurons was not sufficient to account for all aspects of the mice's improvement. Examination of treated mouse brains showed the scientists that the majority of transplanted cells did not replace dead neurons. Instead, most remained as neural stem cells or became supporting cells. These cells stayed near damaged neurons and supplied them with a non-faulty version of the enzyme, which corrects the deficiency that causes debris buildup and cell death. Rescuing dying neurons, in turn, helped reduce inflammation and further loss of neurons. This research demonstrates that transplanted neural stem cells can improve disease symptoms not only by replacing lost or damaged cells, but also by rescuing defective nerve cells and helping reverse disease symptoms such as inflammation. Scientists can take advantage of all of these therapeutic benefits of transplanted cells to develop treatments for Sandhoff Disease and other neurodegenerative diseases that are currently untreatable, including Alzheimer's Disease and Lou Gehrig's Disease (Amyotrophic Lateral Sclerosis, or ALS). Nature Medicine doi: 10.1038/nm1548, laboratory of E.Y. Snyder. 2007 Mar.
- Further Evidence that Mice Can Be Cloned from Adult Stem Cell Types
Scientists have proposed the use of somatic cell nuclear transfer (SCNT) to examine how adult cell nuclei could be reprogrammed and then potentially used to create embryonic stem cells. A group of NIH-supported scientists used SCNT to clone mice by using the nuclei from the sensory neurons found in the nose. These adult stem cells are known for their ability to regenerate themselves. In addition, this finding shows that it is possible to reprogram an adult nucleus by using SCNT. Now, another group of NIH-supported scientists have used the same technique to clone robust and healthy mice using the nucleus from keratinocyte adult stem cells found in a part of the hair follicle called the bulge. These stem cells are involved in hair growth and in repairing skin wounds. In addition, because they reside in the skin, the cells are easily accessible. The oldest of these cloned mice is now nearly two years, which is old age for a mouse. If scientists are able to determine how the adult nucleus is reprogrammed in the egg during SCNT, then they could learn how to reprogram adult stem cells without using SCNT (the egg) to produce pluripotent stem cells that could be used to repair or regenerate certain tissues in the body without the destruction of an embryo. Proceedings of the National Academy of Sciences of the USA 104:2738–2743, laboratory of E. Fuchs. 2007 Feb 20.
- Nonembryonic Human Stem Cells Survive and Mature in Rat Spinal Cord
Scientists are actively pursuing the use of many types of stem cells to treat spinal cord injuries. In 2006, NIH-supported scientists used mouse embryonic stem cells to restore some movement abilities to paralyzed rats. Now, another group of NIH-supported scientists reports that cultured human fetal spinal cord cells survive and mature when transplanted into normal or injured rat spinal cords. The human cells' mature fate depended on their location: those located near the center of the spinal cord became neurons, while those located near a protective membrane called the pia mater stayed immature or matured into a specific type of supporting cell called an astrocyte. Although the cells survived and differentiated, more research will need to determine if the cells actually function and help treated rats recover mobility. However, these results suggest that, at least in rats, the damaged spinal cord does not prevent stem cells from surviving and differentiating. This study provides more hope that scientists may one day be able to use stem cells to treat spinal cord injury and neurodegenerative diseases. PLoS Medicine 4(2):e39, laboratory of V.E. Koliatsos. 2007 Feb 13.
- Found: Stem Cells Responsible for Pancreatic Cancer
Scientific data has shown that the ability of a tumor to grow and spread is dependent on a small group of rogue cells within the tumor, called cancer stem cells. Finding these stem cells is particularly critical for individuals with pancreatic cancer, which has the worst survival rate of any major cancer type. Fortunately, for the first time, privately supported scientists have identified a small population of human pancreatic cancer stem cells. The scientists examined tissue samples from 10 separate pancreatic cancer tumors. The samples then were implanted into mice and aggressively drove tumor formation. When the tumors were examined, the scientists were able to isolate cells that express the characteristics and cellular markers found in stem cells. These pancreatic cancer stem cells composed 1 percent of the total cell population in the tumors grown in the mice. This discovery will help scientists to develop therapeutic approaches to treat pancreatic cancer. Cancer Research 67(3):1030–7, laboratory of D. Simeone. 2007 Feb 1.
- Mother's Stem Cells Passed to Baby—Suggests Possible Way to Treat Diabetes
In type 1 diabetes, an individual's immune system attacks and destroys their own insulin-producing beta cells in the pancreas. Insulin is necessary to efficiently metabolize sugars in foods, and without it, individuals with diabetes must inject themselves with insulin to survive. Scientists are trying to determine why the body attacks its own beta cells, with the hope of developing treatments to halt or reverse the disease process. Umbilical cord blood specimens from male infants contain female cells, believed to cross the placenta from the mother to the child during pregnancy. NIH-funded scientists designed a study to test the hypothesis that in type 1 diabetes, too many maternal cells cross the placenta, contribute to organs in the developing fetus, and stimulate the child's immune system to attack those organs after the child is born. The scientists developed a method for identifying non-child (maternal) DNA in cells and tissues and used it to examine blood samples from individuals with type 1 diabetes, from their siblings who do not have diabetes, and from unrelated healthy individuals. Blood samples from individuals with type 1 diabetes contained more maternal cells than blood from their siblings without diabetes, and significantly higher numbers of maternal cells than in blood from unrelated healthy individuals. The scientists next examined male pancreatic autopsy specimens of children or infants for evidence of maternal cells. Although they found more maternal cells in one specimen from a child with diabetes, the cells did not seem to be under autoimmune attack. Instead, the evidence suggested that the mother's cells had become functional beta cells, helping the child produce insulin after the loss of his own beta cells. The scientists concluded that rather than initiating an immune system attack in individuals with type 1 diabetes, the maternal stem cells may instead increase in number and migrate to the pancreas to replace lost beta cells. They theorize that the child's body tolerates the maternal cells because the immune system is still developing at the time of maternal cell entry into the child's body. They are now investigating this process, and hope to one day use maternal stem cells to treat children with type 1 diabetes. Proceedings of the National Academy of Sciences of the USA 104(5):1637–42, laboratory of E.A.M. Gale. 2007 Jan 30.
- Stem Cell Lines Generated from Amniotic Fluid
Amniotic fluid surrounding the developing fetus contains cells shed by the fetus and is regularly collected from pregnant women during amniocentesis. Scientists have previously reported that some of these cells can differentiate into fat, muscle, bone, and nerve cells. Now, privately funded scientists have generated non-embryonic stem cell lines from cells found in both human and rat amniotic fluid. They named the cells amniotic fluid-derived stem cells (AFS). Tests demonstrate that AFS can produce cells that originate from each of the three embryonic germ layers. The cells are self-renewing and maintain the normal number of chromosomes after a long time in culture. However, undifferentiated AFS did not make all of the proteins expected in pluripotent cells, and they were not capable of forming a teratoma. The scientists developed in vitro conditions that enabled them to produce nerve cells, liver cells, and bone-forming cells from AFS. AFS-derived human nerve cells could make proteins typical of specialized nerve cells and were able to integrate into a mouse brain and survive for at least two months. Cultured AFS-derived human liver cells secreted urea and made proteins characteristic of normal human liver cells. Cultured AFS-derived human bone cells made proteins expected of human bone cells and formed bone in mice when seeded onto 3-D scaffolds and implanted under the mouse's skin. Although scientists do not yet know how many different cell types AFS are capable of generating, AFS may one day allow scientists to establish a bank of cells for transplantation into human beings. Nature Biotechnology 25(1):100–6, laboratory of A. Atala. 2007 Jan.
- Tissue-Matched Stem Cells Created in Mice without Cloning
Scientists have proposed the use of somatic cell nuclear transfer (SCNT) to create stem cells that are tissue-matched to an individual. This process is also known as therapeutic cloning. However, due to exchange of genetic information between pairs of like chromosomes (homologous recombination) during the egg's meiosis, the stem cells created using this method may still not be a precise match for the nucleus donor. In an attempt to improve the degree of tissue-matching, scientists recently derived stem cells from a mouse embryo created using a process known as parthenogenesis. Parthenogenesis describes an embryo created without fertilization of the egg by a sperm, thus omitting the sperm's genetic contributions. The scientists identified stem cell lines retaining the identical "self" genetic information of the egg donor and used them to generate tissues for transplantation into the egg donor. These transplanted tissues were not rejected by the egg donor mouse's immune system. If scientists can repeat this technique using human eggs, they may be able to generate tissue-matched cells for transplantation to treat women who are willing to provide their own egg cells for this purpose. This technique could also offer an alternative method for deriving tissue-matched human embryonic stem cells that does not require destruction of a fertilized embryo. Science 315:482–6, laboratory of G.Q. Daley. 2007 Jan 26.
- Multipotent Adult Progenitor Cells (MAPCs) Regenerate Blood in Mice
In 2001, scientists isolated a special type of non-blood stem cells from human bone marrow. They named these cells multipotent adult progenitor cells, or MAPCs. MAPCs are able to generate cells of all three embryonic germ layers. Initially, MAPCs were notoriously difficult to isolate and grow in culture. In 2006, scientists reported improved MAPC isolation and culture conditions. Now a collaborative group of NIH-supported scientists successfully used mouse MAPCs to regenerate the blood-forming system in mice. The scientists speculate that MAPCs may arise earlier in development than blood-forming stem cells, because transplanted MAPCs generated both long-term blood-forming stem cells and all types of early blood cells. Although MAPC-derived cells that did not make blood-specific proteins (i.e., not blood cells) were identified in tissues outside of the blood, they also did not make proteins characteristic of the tissue in which they were found. The scientists have not yet determined the identity of these cells. Transplanted MAPC-derived cells did not appear to form tumors in recipient mice. MAPCs' ability to grow and divide in culture and to regenerate the blood-forming system in mice provides hope that scientists may be able to use human MAPCs to treat diseases of the blood. Doctors may also be able to induce transplant tolerance in human beings by using MAPCs to generate both immune cells and tissues for repair or replacement. The Journal of Experimental Medicine 204(1):129–39, laboratory of C. Verfaillie. 2007 Jan 22.