2004 Articles
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.
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- New Method for Obtaining Human Embryonic Stem Cells
Privately funded scientists have developed a new method for obtaining human embryonic stem cells (hESCs.) Unlike the established method, which uses 5-day-old (blastocyst stage) embryos, the new method uses 4-day-old (morula stage) embryos. The authors report that the morula-derived hESCs appear to be similar to blastocyst-derived hESCs in their shape, marker expression, and in their ability to spontaneously differentiate into the variety of cell types that make up embryoid bodies. (Reproductive Biomedicine Online 9:623–629, Reproductive Genetics Institute)
- Stem Cell Nucleus Vital for Reprogramming Differentiated Cells after Fusion
As cells in the developing embryo divide, some of the resulting daughter cells begin to express genes characteristic of a specific cell type, such as a nerve cell or liver cell. As part of this process, cells gradually "turn off" or inactivate, genes not needed to function as their specific cell type. This process is referred to as differentiation. The gradual gene inactivation results in a corresponding gradual loss of the ability to become any type of cell. Put another way, the differentiated cells are no longer pluripotent. Scientists have been able to reprogram differentiated cells by fusing them with embryonic stem cells (ESCs). However, the location and identity of the ESC factors that enable reprogramming are still unknown. Recently, NIH-supported scientists compared the ability of ESC nuclei versus ESC cytoplasm to reprogram differentiated cells. They found that ESC nuclei could reprogram the differentiated cells after fusion but ESC cytoplasm could not do so. This research suggests that scientists may now focus their search for reprogramming factors on the ESC nucleus. (Stem Cells 22:941–949, laboratory of H.R. Schöler)
- Adult Stem Cells Could Help Regenerate Skin and Hair
Adult stem cells are usually difficult to isolate. Once isolated, the cells tend to differentiate in culture. These two difficulties present a barrier to the use of adult stem cells for treating human disease. NIH-supported scientists may have found a way to overcome these barriers, at least for skin and hair. The scientists used skin-specific stem cell surface markers to isolate two distinct populations of mouse hair follicle stem cells - neatly packaged into a structure called the bulge. Under normal conditions, the two stem cell populations play different roles in hair development and growth. In laboratory cultures, stem cells isolated using this novel method grew readily and maintained their undifferentiated characteristics. When grafted onto the wounded skin of hairless mice, both populations of stem cells produced both skin and hairs. Researchers may now use this technique to search for similar skin and hair stem cells in humans. If identified, human adult skin and hair stem cells could lead to treatments for burns and other skin conditions, and may also treat hair loss. (Cell 118:635–48, laboratory of E. Fuchs)
- Injected Stem Cells Prevent Heart Birth Defect in Mice
Id proteins (Id1–Id4) regulate cell differentiation in many different organs, including the heart, in mice and humans. NIH-supported scientists studying mice that lack several copies of the Id1, Id2, and Id3 genes noted severe heart defects that caused the embryos to die before birth. However, the hearts of Id knockout mice injected at approximately 5 days with labeled mouse embryonic stem cells appeared similar to those of their wild-type littermates. The label allowed the scientists to observe where the stem cells went and what they became. Regions of the heart that did not contain stem cells (no label) still appeared to be rescued after stem cell injection. This suggests that the injected stem cells secrete something that diffuses throughout the heart and rescues its development. The scientists present evidence that the stem cells secrete Insulin-like Growth Factor 1 (IGF-1), which interacts with another protein called WNT5a to rescue the heart defects and restore normal gene expression in stem cell-injected knockout mouse hearts. If researchers determine that human embryonic stem cells also release IGF-1–like factors and they work the same way in humans, doctors may one day be able to inject stem cells or the factors that they secrete to correct developmental defects in human embryos before birth. Science 306:247–252, laboratory of R. Benezra)
- Heart Muscle Cells Produced from Human Embryonic Stem Cells Can Replace Biological Pacemaker
A heart attack occurs when the supply of blood and oxygen to an area of heart muscle is blocked. Often, this blockage leads to arrhythmias (irregular heartbeat or rhythm) that cause a severe decrease in the pumping function of the heart and may bring about sudden death. If the blockage is not treated within a few hours, the affected heart muscle will die and be replaced by scar tissue. Transplantation of heart muscle cells is one possible therapy, but supplies of such cells are very limited. Scientists supported by the Israeli government and private funds produced heart muscle cells from human embryonic stem cells (hESCs) listed on the NIH Stem Cell Registry. The hESC-derived heart muscle cells beat in synchrony with newborn rat heart muscle cells after being cultured together for 24 hours. Transplanted hESC-derived heart muscle cells were also able to restore heart rhythm in 11 out of 13 pigs whose biological pacemaker had been damaged. If this work can be repeated in human beings, scientists may be able to use these cells to replace human heart pacemakers rather than the current implanted electronic devices. (Nature Biotechnology 22:1282–1289, laboratory of L. Gepstein)
- Human Embryonic Stem Cells May Help Treat Vision Loss
Retinal pigment epithelium (RPE) cells within the eye play a vital role in the survival and maintenance of the rods and cones that detect light and color. Death of RPE cells may lead to age-related macular degeneration (AMD)(PDF file; get Adobe Reader), a major cause of vision loss in persons aged 60 and older. Privately funded investigators derived RPEs from human embryonic stem cells (hESCs) listed on the NIH Stem Cell Registry and from hESCs derived using private funds. They compared gene expression in these cells to isolated fetal RPE cells and existing fetal RPE cell lines. The gene expression pattern suggests that RPEs derived from hESCs are more like normal RPEs than existing fetal RPE lines. If these cells can successfully restore vision to animal models of AMD, they may be tested as a treatment for human AMD. (Cloning and Stem Cells 6:217–245 (PDF file; get Adobe Reader), laboratory of R. Lanza)
- Researchers Identify Multipotent Cells in Pancreas of Adult Mice
Beta (β) islet cells within the pancreas make the insulin that is critical to regulate blood sugar. Earlier this year, scientists reported that most β islet cells found in an adult mouse were produced by division of β islet cells already present in its early life and did not originate from adult stem cells. (see New Insulin-Secreting Cells Produced by Self-Duplication and Not Adult Stem Cells.) Although this suggests that normal pancreas maintenance involves self-duplication, it does not rule out the possibility that the adult pancreas contains stem cells. New research by Canadian-funded scientists suggests that there may indeed by stem cells in the adult mouse pancreas. The scientists isolated single adult pancreatic cells and grew them under conditions that encouraged colony formation. As cells of the colonies differentiated, they expressed genes characteristic of many different cell types, including pancreatic β islet cells. The putative β islet cells secreted insulin, and when sugar was added to the medium, the cells increased their production of insulin. If these results can be repeated with human pancreatic cells, scientists may have a promising new source of replacement cells for treating diabetes. (Nature Biotechnology 22:1115–1124, laboratory of D. van der Kooy)
- A Step Closer to Stem Cell-Derived Treatment for Parkinson's Disease
Scientists are getting closer to their goal of replacing the human dopamine-producing nerve cells (dopaminergic neurons) lost in Parkinson's disease. In an earlier highlight (Stem Cells Improve Motor Function in Rat Model of Parkinson's Disease), scientists reported that they had successfully derived dopaminergic neurons from mouse embryonic stem cells. Now, scientists report that they have developed a culture technique to produce dopaminergic nerve cells from human embryonic stem cells. By mimicking conditions inside the developing human midbrain, they produced neurons that behaved and looked similar to those lost in Parkinson's disease. Because these neurons were created using human cells, they offer scientists a unique opportunity to test preclinical therapies for Parkinson's disease and to gain a better understanding of how the human midbrain develops. (Proceedings of the National Academy of Sciences of the USA 101:12543–8, laboratory of L. Studer)
- Skin Cancer Cell's Nucleus Can Be Used to Produce Normal Stem Cells
Cancer cells are abnormal and divide without control. The disease begins when a cell's genes suffer a mutation, or when a previously silent inherited mutant gene is somehow "turned on." Melanoma is a form of skin cancer that arises in melanocytes, the cells that produce pigment. NIH-supported scientists transferred a mouse melanoma cell nucleus into a mouse egg whose nucleus was removed, thus creating an embryo using somatic cell nuclear transfer (SCNT). They then used the SCNT embryo to derive mouse embryonic stem cells (mESCs). When the scientists injected these mESCs into developing mouse embryos, the mESCs contributed to different tissues in the mice's bodies. This suggests that cancer is not the inevitable fate of a cancerous cell. However, the mice that were generated using these processes were more likely to develop tumors than normal mice. Scientists may now use this technique to study how the damaged or mutated genes present in the nucleus of cancer cells actually cause the disease. (Genes and Development 18:1875–1885, laboratory of R. Jaenisch)
- Mouse Neural Stem Cells Capable of Becoming Blood Vessel Cells
Researchers are actively investigating the differentiation potential of adult brain stem cells. While some studies suggest that these cells can become many different cell types, other studies suggest that they may instead be fusing with existing cells when transplanted. A group of NIH-supported researchers grew mouse brain stem cells in culture dishes along with human endothelial (blood vessel lining) cells. The researchers used mouse brain stem cells that expressed a green fluorescent protein for easy identification. After 2-5 days, approximately 6% of the green mouse brain stem cells expressed endothelial cell markers. A fused mouse/human cell would contain two nuclei and both mouse and human chromosomes. The researchers observed that each green cell expressing endothelial markers contained only one nucleus that, in turn, contained only mouse chromosomes. These observations suggest that the mouse brain stem cells became mouse endothelial cells rather than fusing with existing human endothelial cells. When transferred to culture conditions that promote blood vessel growth, the green mouse endothelial cell candidates were able to aggregate and elongate to form blood-vessel like structures. This work provides evidence that adult brain stem cells may have greater potential than was previously believed. (Nature 430:350–356, laboratory of F.H. Gage)
- Scientists Isolate Adult Stem Cells That May Help Treat Gum Disease
The National Institute of Dental and Craniofacial Research (NIDCR) estimates that up to 80% of adults in the U.S. have some form of gum disease. Untreated gum disease is a major cause of tooth loss. Although scientists have long suspected that the gums contain stem cells responsible for gum repair and maintenance, they had difficulty finding gum stem cells. A group of NIH-supported scientists recently isolated adult gum stem cells from a fragment of the tissue that remains on extracted wisdom teeth. The tissue fragment is part of the periodontal ligament, a fibrous tendon that holds teeth in their sockets. When transplanted into rodents, the human gum stem cells were able to generate cementum, a hard tissue layer that covers tooth roots, and helped repair gum damage. These easily obtainable adult stem cells may one day be used as a treatment for human gum disease. (Lancet 364:149–155, laboratory of S. Shi)
- Large-Scale Culture Method to Produce Blood Cells from Human Embryonic Stem Cells
Ideally, researchers would like to grow large quantities of human embryonic stem cells (hESCs) and coax them into becoming specific cell types, but such cultures are difficult to maintain. The best method for generating specific cell types from hESCs is to allow them to aggregate into rounded structures called embryoid bodies (EBs.) The 3-D structure of EBs imitates early embryonic development and promotes the cell-cell and cell-environment interactions necessary for producing different cell types. However, when EBs are added to the rotating stirred canisters used for large-scale culture, they clump together into even larger masses, resulting in poor cell growth and low production rates of specific cell types. Non-NIH supported investigators developed a method for enclosing individual EBs in gelatin capsules. After encapsulation, EBs no longer mass together and can successfully be added to large-scale stirred cultures. Stirred cell culture permits tight control and precise measurement of media conditions. The researchers efficiently generated blood-forming stem cells by manipulating the amount of oxygen within each canister. Other researchers may now be able to adapt this method to produce large numbers of specific cell types from hESCs. (Stem Cells 22:275–282, laboratory of P. Zandstra.)
- New Insulin-Secreting Cells Produced by Self-Duplication and Not Adult Stem Cells
As part of the normal aging process, the human body replaces damaged or aging cells. Scientists studying this process are trying to determine the source of replacement cells in the adult pancreas, whose β islet cells produce the insulin that regulates blood sugar. Privately funded scientists labeled β islet cells of young mice in order to determine if these cells were the source of replacement β islet cells in the adult mouse. Their analyses suggested that most β islet cells found in an old or middle-aged mouse were produced by division of β islet cells already present in its early life and did not originate from adult stem cells. A mouse whose pancreas was partially removed also regenerated it using existing β islet cells and not stem cells. These results demonstrate that adult β islet cells are still capable of self-duplication and cast doubt on the idea that adults have a supply of stem cells that help replace old or damaged pancreatic β islet cells. If human β islet cells also remain capable of self-duplication, scientists may be able to boost this process in individuals with diabetes to restore their ability to regulate blood sugar. (Nature 429:41–6, 2004, laboratory of D. Melton)
- Growing Human Embryonic Stem Cells without Animal Products
Ideally, stem cells used to treat human beings will be grown without exposure to animal products such as the mouse embryonic fibroblasts (MEFs) or MEF extracts used in standard human embryonic stem cell (hESC) cultures. NIH-supported researchers tested the ability of several combinations of growth factors, combined with serum replacement and fibronectin matrix, to support and maintain cultured hESCs in the undifferentiated state. (For more information about growth factors, see Scientists Identify Factors Critical to Growth of Embryonic Stem Cells.) The cell lines used are all listed on the Stem Cell Registry and were first cultured on MEFs, then transferred to the medium being tested. The researchers identified two combinations of growth factors that enabled continued hESC division while retaining normal hESC features. The two combinations included either transforming growth factor beta (TGFB) and basic fibroblast growth factor (bFGF), or TGFB and bFGF with the addition of leukemia inhibitory factor (LIF). This work brings stem cell research closer to the use of animal-free culture systems and may one day help researchers develop standardized animal-free human stem cell therapies. (Biology of Reproduction 70:837–845, 2004, laboratory of J. Itskovitz-Eldor)
- What Can We Learn from Stem Cells in Fruit Flies?
Scientists eager to identify stem cell development and maintenance genes are studying fruit flies because their speedy reproductive cycle and well-described genetics enable scientists to test the function of a specific gene. During normal development, cells that could initially become almost any cell type become progressively more and more restricted in fate—a process called differentiation. When a differentiated cell changes back into a less differentiated cell, it is called dedifferentiation. Privately funded scientists reported that they could manipulate fruit fly gene expression to force differentiating early egg cells to dedifferentiate into multipotent stem cells. If this feat can be accomplished in higher organisms, it will provide scientists with a non-controversial source of stem cells. In a separate study, NIH-supported scientists identified a fruit fly gene that serves two important roles in egg stem cell differentiation. Experiments using flies that lack the gene, Nanos, suggest that flies must express Nanos if they are to develop a supply of early egg stem cells (called primordial germ cells.) Nanos is also required for the flies to maintain a supply of egg stem cells in adulthood. Scientists may one day be able to use their knowledge of fruit fly stem cell genes to "turn on" stem cell formation in adult organisms. (Nature 428:564–569, laboratory of A. Spradling; Science 303:2016–2019, laboratory of H. Lin)
- Stem Cell Therapy for the Heart: Hope and Controversy
Scientists worldwide are actively pursuing stem cell therapies to treat heart disease. Small clinical trials and anecdotal accounts suggest that stem cells can regenerate heart muscle and restore some of the heart's blood pumping ability. However, these therapies have not been tested in large-scale clinical trials, and the type of stem cells used, stem cell purification methods, and outcome measures of small clinical trials vary widely. Another major concern is scientists' ability to track the fate of injected cells. Work done in animal models is still providing important information about stem cells as heart therapies. Two separate groups of NIH-supported researchers tested the ability of blood-forming (hematopoietic) stem cells to regenerate heart muscle tissue in mice following an induced heart attack. They injected labeled hematopoietic stem cells into the damaged region of the heart muscle. Later examination of the heart demonstrated that injected cells continued to express hematopoietic cell proteins and did not fuse with heart cells or express proteins characteristic of heart cells. These findings contradict previous reports that injected hematopoietic stem cells assume new identities in the heart and add to the continued debate over the use of these cells as therapy for human heart disease. (Nature 428:668–673, laboratory of R. Robbins; Nature 428:664–668, laboratory of L. Field)
Two recent papers published in Lancet described the effects of injecting unlabeled stem cells into the heart's blood vessels. In a clinical trial supported by the South Korean government, scientists used a drug to increase the number of circulating blood stem cells in heart attack patients and then used those cells to treat their damaged hearts. Contrary to previous reports, treated patients did not suffer rapid heartbeat or apparent inflammation after cells were injected. Although treated patients demonstrated increased exercise capacity and heart pumping abilities, they also tended to develop narrowing of a previously widened heart artery, so the trial was stopped prematurely. Using private funds, another group of scientists tested the safety of mesenchymal stromal cells, stem cells found in bone marrow that normally produce cartilage and other connective tissues. They collected mesenchymal cells from bone marrow of healthy dogs, expanded the cells in culture, and then injected them into the heart blood vessels of the same dogs. Electrocardiograms showed that the dogs suffered from short term rapid heart rate and localized blood vessel blockage within the heart as the cells were injected. Blood tests on two dogs suggested that their heart muscles had suffered some tissue death. Post-mortem examination of the dogs' hearts confirmed that they had suffered mini heart attacks, presumably the result of stem cell injection. The researchers propose that the large size of the injected stem cells may have blocked blood vessels and caused the heart attacks. The data from all of these studies should encourage caution in the pursuit of stem cell therapies for treating human heart disease. (Lancet 363:751–756, laboratory of Y.-B. Park; Lancet 363:783–784, laboratory of M. Kittleson)
- A Challenge to Developmental Dogma: Adult Mammals May Yet Produce Eggs
Developmental biology textbooks teach students that most female mammals are born with all of the eggs they will ever produce. Now the research of NIH-supported scientists may change what students learn. Using mouse ovaries, the scientists analyzed how many eggs were degenerating and how fast degenerate eggs were cleared from the ovaries. Based on these data and on the number of eggs developing in the ovaries at any one time, they surmised that the mice must be continuously renewing their egg supply. They tested this idea by blocking cell division and found that treated mice had no eggs remaining by the time they reached adulthood. The scientists identified cells in adolescent and adult mouse ovaries simultaneously expressing both immature egg cell and cell division markers. They transplanted unlabeled ovaries into mice whose cells express green fluorescent protein (GFP) and found that the transplanted ovaries were infiltrated by green cells that developed into mature eggs. These studies all provide evidence that, contrary to the 50-year old developmental dogma, adult mammals have a reserve pool of ovarian stem cells capable of developing into eggs. If confirmed by other laboratories, this work promises to open new areas of study in human fertility. (Nature 428:145–150, laboratory of J. Tilly)
- Human Stem Cell Pluripotency Genes Located on Same Chromosome
Human embryonic stem cells (hESCs) are considered "pluripotent" because they can divide to produce cells of almost any tissue or organ in the body. In order to understand what gives stem cells their unique abilities, scientists must first identify which genes are important for pluripotency. In search of more pluripotency genes, NIH-supported scientists focused on human chromosome 12 p, where the known pluripotency gene OCT-4 is located. They identified three likely candidates. The genes, called STELLAR, NANOG, and GDF3, are active when hESCs are undifferentiated and are less active as hESCs assume a more mature identity. The authors note significant expression and sequence differences between the mouse and human versions of these genes. By working to identify the functional roles of these genes, scientists will gain a better understanding of how stem cells remain pluripotent. (Stem Cells 22:169–179, laboratory of R. Pera)
- Chromosomal Changes Reported in Cultured Human Embryonic Stem Cells
If human embryonic stem cells are to be used as therapies for human diseases, scientists must verify that the cell lines' chromosomes are stable. Experience with mouse embryonic stem cells demonstrates that they become unstable after prolonged culture. A group of scientists supported by the United Kingdom recently reported changes in the structure and number of chromosomes in some of the human embryonic stem cell lines listed on the NIH Stem Cell Registry. This is the first published report of such changes, although there are similar but unpublished anecdotal observations from other laboratories around the world. The chromosomal changes observed are similar to those commonly found in embryonic carcinomas, which are cancers of stem cells. These data serve as a warning to scientists developing culture conditions for human embryonic stem cells. Long-term culture and/or culture under feeder-free conditions seem to select for undesirable changes in their chromosomes. Using cells with unstable chromosomes to treat human diseases could result in cancer or produce other undesirable side effects. (Nature Biotechnology 22:53–54, laboratory of P. Andrews)
- Drug Enables Stem Cells to Remain Pluripotent in Culture
One big problem facing scientists interested in comparing different human embryonic stem cell lines is that each cell line requires different growing conditions in order to remain undifferentiated. The growing conditions usually include the use of animal-derived products such as feeder cells and serum that are impossible to standardize. Ideally, scientists would like to determine what key factors the feeder layers or serum provide and develop growing conditions that replace them with drugs or other factors that can be standardized. Now a research team supported by the Rockefeller University and the French government has identified a drug that can keep stem cells undifferentiated. The drug, 6-bromoindirubin-3'oxime (BIO), activates a key signaling pathway in both mouse and human embryonic stem cells (ESCs). Cultured ESCs treated with BIO express genes considered to be hallmarks of undifferentiated cells, and withdrawal of BIO leads to ESC differentiation. Scientists may one day be able to use drugs such as BIO to grow human ESCs in culture without the need to use animal serum and cell products. (Nature Medicine 10:55–63, laboratory of A. Brivanlou)
- Signature Genes for Pluripotent Cells
Determining the potential of various types of cells is a critical first step towards using them to develop cell-based therapies to treat human diseases and to repair tissue damage. NIH-supported scientists compared gene expression in a spectrum of mouse cells ranging from unfertilized eggs to adult cells in order to identify genes characteristic of pluripotent cells. They identified a set of genes that is highly expressed in eggs, fertilized eggs, and embryonic stem cells. Post-implantation cells expressed lower levels of this gene set, and they found a continued decrease in expression levels in cells from more differentiated tissue. Thus, the expression level of this set of genes can be used to judge a cell's potential. The scientists have posted a Microsoft Excel chart with information on this set of genes on the Internet and hope that broad access to the data will help to rapidly advance research in reproductive and regenerative medicine. (PLoS Biology 1:410–419 [570KB PDF file; get Adobe Reader], laboratory of H. Ko—NIA)
- New Methods to Determine Gene Function in Human Embryonic Stem Cells
Determining the function of a gene can be complicated. Scientists use genetic engineering to add or remove specific genes within animal embryos, and evaluate the animals after birth to determine the effects of too much or too little of the targeted gene. However, the process is time consuming. Since mammalian DNA contains two copies of most genes, scientists trying to remove a gene must go through two rounds of genetic engineering to remove both copies. Researchers supported by the United Kingdom tested alternative methods for increasing and decreasing the expression of a specific gene within human embryonic stem cells (hESCs.) They used an established technique (called lipofection) to insert the genes for red or green fluorescent proteins into hESCs. The hESCs survive the procedure, make red or green fluorescent proteins, and maintain their ability to generate many different types of cells (pluripotency). This experiment suggests that scientists could use this method to insert a "promoter" to increase expression of a specific gene in hESCs without robbing them of their essential stem cell qualities. The fluorescent proteins used to demonstrate this technique will provide the additional benefit of permitting scientists to track the cells' fate if they are transplanted. The same group of scientists was also able to use a technique called RNA interference (RNAi) to substantially decrease expression of a targeted hESC gene. RNAi recruits a cell's defense mechanisms to destroy both the artificially inserted RNA and any similar RNA within the cell. This method of reducing a gene's RNA transcripts is faster than traditional genetic engineering methods and targets the RNA made from both copies of the gene simultaneously. These techniques for tracking and modifying gene expression in hESCs provide an invaluable way for researchers to study how hESCs remain pluripotent and how they differentiate. (Stem Cells 22:2–11, laboratory of R.A. Pedersen)
- A Review of Adult Stem Cell Plasticity
A well-respected scientist from the United Kingdom's Medical Research Council reviews the field of adult stem cell plasticity, including terminology, types of adult stem cells, claims for adult stem cell plasticity, problems and controversies in adult stem cell research, and the dedifferentiation and conversion of precursor cells to stem cells. (Annual Review of Cell and Developmental Biology 19:1–22, M. Raff)
- Mouse Sperm Generated from Stem Cells Able to Fertilize Mouse Egg
Earlier in 2003, Japanese scientists were able to generate mouse sperm using mouse embryonic stem cells (see Mouse Embryonic Stem Cells Develop into Sperm). Now, a group of NIH-funded scientists in Massachusetts has generated sperm from mouse embryonic stem cells and demonstrated that they can fertilize a mouse egg. Because the sperm cells did not have a tail, the scientists had to inject them into mouse eggs to accomplish fertilization. Scientists may now be able to generate sperm in the laboratory to study how they regulate gene expression and other important events during development. (Nature 427:148–154, laboratory of G.Q. Daley)
- Scientists Identify Factors Critical to Growth of Embryonic Stem Cells
Growth factors enable stem cells to keep dividing to produce more stem cells, to remain undifferentiated, and to maintain their ability to produce almost any cell in the body. In the laboratory, embryonic stem cells get growth factors from mouse or human "feeder cells" included in the culture dish and from serum in the media, a broth that covers the cells. Scientists are concerned that feeders and serum may pass diseases to embryonic stem cells, so they are working to identify which growth factors are critical. Scientists may then grow them without using any animal products (usually found in serum) or feeder cells. A team of scientists supported by the United Kingdom recently identified a type of growth factors critical for mouse embryonic stem cells. The factors, called BMPs, for bone morphogenetic proteins, initiate a series of signals inside the stem cells that keeps them undifferentiated. The team was able to grow mouse embryonic stem cells in culture without feeders or serum if they added BMP and a previously identified factor (Leukemia Inhibitory Factor, or LIF) to the media. If scientists can adapt this technique to the growth of human embryonic stem cells, it will be a major step towards the use of these cells to treat human disease and injury. (Cell 115:281–292, laboratory of A. Smith)
- Stem Cells Found in Children's Brain Tumors
NIH-funded scientists have isolated stem cells from four types of children's brain tumors. The tumor cells have characteristics of neural stem cells, including the ability to migrate, to self-renew, and to produce different kinds of nervous system cells. However, they also differ from normal nervous system stem cells: they live longer and divide to make cells with abnormal features. Scientists may be able to use what they learn from these cells to target and destroy stem cells within children's brain tumors. These tumor stem cells are believed to be the self-renewing cell population in these tumors. (Proceedings of the National Academy of Sciences of the USA 100:15178–15183, laboratory of H.I. Kornblum)
- Tissue Engineering in Rats May Pave the Way for Human Joint Replacement
Scientists supported by NIH have succeeded in coaxing adult rat bone marrow stem cells to form a mandibular condyle, a critical part of the human jaw joint that is prone to damage and disease. The scientists treated the stem cells with bone and cartilage-inducing growth factors. The cells were then suspended in a gel and grown within a mold of the human jaw joint. The growing construct was hardened and then implanted under the skin of a mouse host. The rat cells formed cartilage and bone in layers and in a shape similar to a human mandibular condyle. This work using rat bone marrow stem cells is a critical first step towards the use of human stem cells to replace human joints damaged by injury or diseases such as arthritis. (Journal of Dental Research 82: 951–956, laboratory of J.J. Mao)
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