elastin and Central-Nervous-System-Diseases

Cellular transplantation therapy is thought to play a central role in the concept of restorative neurosurgery, which aims to restore function to the damaged nervous system. Stem cells represent a potentially renewable source of transplantable cells. However, control of the behavior of these cells, both in the process of clonogenic expansion and post-transplantation, represents formidable challenges. Stem cell behavior is thought to be directed by extracellular signals in their in vivo niches, many of which are protein or peptide based. As only one example, activation of Notch plays an important role in normal development and is the strongest known signal for stem cells to choose glial over neuronal fates. Therefore, artificial extracellular matrix proteins represent a potentially powerful tool to custom design artificial niches to strategically control stem cell behavior. We have developed a family of aECM proteins that incorporate the active domains of the DSL ligands to the Notch receptor into an elastin-based backbone. The development of our DSL-elastin artificial proteins demonstrates the design strategy and methodology for the production of bioactive artificial extracellular matrix proteins aimed at modulating stem cell behavior, and this method can be used to design other bioactive aECM proteins. In addition, we have developed a method for the isolation and characterization of adult human neural stem cells from periventricular tissue harvested from living patients. This paper reviews cellular transplantation therapy from the clinical perspective and summarizes ongoing work aimed at exploring the intriguing possibility of autologous transplantation, whereby neural stem cells can be harvested from adult patients, expanded or modified in vitro in artificial niches, and retransplanted into the original patient.

Topics: Adult; Calcium-Binding Proteins; Cell Transplantation; Central Nervous System Diseases; Elastin; Extracellular Matrix; Humans; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Models, Biological; Neurons; Proteins; Receptors, Notch; Serrate-Jagged Proteins; Signal Transduction; Stem Cell Transplantation; Stem Cells; Transfection; Transplantation, Autologous

Copper, as a component of numerous cuproenzymes, plays a vital role in many physiologic functions in man and animals. From the stand-point of human health there are at least three functional areas of prime importance. Copper is involved in the development and maintenance of cardiovascular and skeletal integrity, central nervous system structure and function, and erythropoietic function including iron metabolism. Although there is no evidence for widespread copper deficiency in the human population, it does occur, owing to genetic defects and other precipitating factors. A clear understanding of the functions of copper and its mechanisms of action could prove highly beneficial in the solution of present and unforeseen problems in medicine.

Topics: Anemia; Animals; Bone Diseases; Brain Diseases; Cardiovascular Diseases; Central Nervous System Diseases; Collagen; Copper; Deficiency Diseases; Elastin; Enzymes; Female; Growth Disorders; Hair; Humans; Infant; Infant, Newborn; Metalloproteins; Pigmentation Disorders; Pregnancy; Pregnancy Complications; Protein-Lysine 6-Oxidase