Improve development and testing of drugs: A detailed understanding of stem cell regulation and the molecules that affect it would provide new targets for pharmacological interventions. Stem cell culture systems would also make possible rapid and economical testing of candidate agents for both effectiveness and safety.
Mental Health Research
There is good evidence that many of the mental and behavioral disorders such as schizophrenia, autism, manic-depressive illness and memory disorders, result from permanent disruption of brain circuitry or brain chemistry.
The National Institute of Mental Health (NIMH) is currently supporting many research grants to determine exactly where and how such brain disruptions may occur, and is encouraging a vigorous program of research, including stem cell research with animals, to develop disease models and understand basic neuronal processes. For example, scientists are using non-human primate models to explore the hypothesis that schizophrenia is the result of damage to brain cells that mature at a particular stage of human development. If this hypothesis is supported, pluripotent stem cell research might provide a window into what goes wrong in the brain in schizophrenia, as well as potential interventions to remediate this devastating illness. Similar hope may apply to the severe developmental disorders, such as autism.
In another arena, investigators are examining stress- and toxin-induced loss of cells in a brain structure important for memory, the hippocampus. Animal studies have shown that natural replacement of cells in the hippocampus, via stem cells, results in improved memory performance as long as another important structure for memory, the cerebral cortex, is largely intact. Human pluripotent stem cells might ultimately be important to the development of replacement cells in the hippocampus of humans suffering from memory loss caused by selective damage to the hippocampus.
On Eyes
Treatment of Retinal Degenerations: Some promising results have been obtained transplanting retinal cells and tissues in an effort to "treat" animal models of retinal degeneration. However, the results have been mixed and many questions remain. The immunologic issues governing transplant survival are complex and only partially understood. Possible strategies for overcoming these problems are suggested from ongoing investigations of the development and maturation of the normal retina. Cell lineage analysis has shown that retinal cells are generated from progenitor cells throughout development. The cell types generated in vitro can be influenced by the environment, and certain growth factors added to retinal cell cultures can lead to shifts in the types of cells produced. Growth factors can also influence the survival of retinal cells in vitro or in vivo. In addition to the effect of extrinsic cues, intrinsic properties of progenitor cells contribute to the genesis of retinal cell types as well. These types of experiments may lead to more effective strategies whereby manipulation of these progenitor cells could be exploited for retinal transplantation therapies. However, these experiments may also reveal insurmountable difficulties associated with this limited approach. In which case, use of pluripotent stem cells would become essential to overcome the immunological or other potential problems that may be encountered.
Treatment of Ocular Surface Disorders: There is a significant clinical need for improved techniques to promote conjunctival and corneal healing during disease or after injury. Conventional surgery is not consistently successful in treating persistent corneal ulcers, chemical or thermal injury, bullous keratopathy, and various cicatrical diseases. Transplantation with pluripotent stem cells could provide a means of facilitating epithelialization of the ocular surface, reducing inflammation, vascularization, and scarring.
Dental and Craniofacial Research
Pluripotent human stem cells offer an important new tool and resource in biomedical research. Research using animal pluripotent stem cells is already helping to improve our understanding of the complex events of tissue development and regeneration. In addition, it is providing new approaches for the development and testing of new drugs and therapies and is contributing to the development of new technologies for the repair and replacement of organs, which have been damaged by disease or injury.
This is but a glimpse of what promises to become a rapidly expanding research portfolio at NIDCR. Stem cell research should better allow us to understand the biology of inherited craniofacial anomalies such as cleft lip and cleft palate and also the way normal cells can become malignant in orofacial and pharyngeal cancer. This should provide new information to prevent and treat these diseases. In addition, stem cell research could lead to the engineering of specialized cells such as bone, cartilage and salivary cells, which can be used as replacement for organs damaged by disease or injury. Examples include the treatment of temporomandibular joint disorders (TMDs), the replacement of skeletal elements lacking or damaged in diseases such as fibrous dysplasia of bone using cells grown in special natural or synthetic scaffolding materials, and the replacement of salivary cells damaged by disease (Sj鰃ren's Syndrome) or radiation for head and neck cancer.
Embryonic stem (ES) cells are continuously growing stem cell lines of embryonic origin first isolated from the inner cell mass of developing mouse blastocysts. More recently, it has been shown that embryonic germ (EG) cell lines, established from primitive reproductive cells of the fetus, are functionally equivalent to ES cells. The distinguishing features of ES cells are their capacity to be maintained in an undifferentiated state indefinitely in culture and their potential to develop into every cell of the body. The most rigorous test of the developmental potential of mouse ES cells is their ability to contribute to all cell lineages—including the germ–line—of chimeric animals. In addition, under appropriate culture conditions, ES cells differentiate into a broad spectrum of cell types and when injected into immunocompromised animals, they form teratomas composed of multiple lineages. It is this ability to develop into a wide range of cell types that has drawn so much attention to ES cells as a basic research tool and as a novel source of cell populations for new clinical therapies.
Given the outstanding potential demonstrated by mouse ES cells, it was anticipated by
