Edward Donnall Thomas, an American physician and scientist, gained recognition in the scientific community for conducting the first bone marrow transplant, a pioneering form of hematopoietic stem cell transplantation (HSCT). Bone marrow transplants are considered to be the first successful example of tissue engineering, a field within regenerative medicine that uses hematopoietic stem cells (HSCs) as a vehicle for treatment. Prior to Thomas's groundbreaking work, most blood-borne diseases, including certain inherited and autoimmune diseases, were considered lethal.
In the early 2000s, Manjong Han, Xiaodang Yang, Jennifer Farrington, and Ken Muneoka investigated how genes and proteins in fetal mice (Mus musculus) influenced those fetal mice to regenerate severed toes at Tulane University in New Orleans, Louisiana. The group used hind limbs from mice to show how the gene Msx1 (Homeobox 7) functions in regenerating amputated digits. The researchers showed that in the process of regenerating digit tips, Msx1 genes make products that regulate or influence other genes, such as the Bone Morphogenetic Protein 4 gene (BMP4 gene), to produce proteins, such as the BMP4 proteins. The researchers also showed that BMP4 proteins, which are produced from the BMP4 gene, function in tissues during the process of limb development. Furthermore, while Msx1 genes regulate other genes during the process of regeneration, they don't produce proteins otherwise needed to organize cells in the regeneration of digit tissues. The group published their results in 2003 as Digit Regeneration Is Regulated by Msx1 and BMP4 in Fetal Mice.
In 2012, a team of scientists across the US conducted an experiment to find the mechanism that allowed a group of flatworms, planarians, to regenerate any body part. The group included Danielle Wenemoser, Sylvain Lapan, Alex Wilkinson, George Bell, and Peter Reddien. They aimed to identify genes that are expressed by planarians in response to wounds that initiated a regenerative mechanism. The researchers determined several genes as important for tissue regeneration. The investigation helped scientists explain how regeneration is initiated and describe the overall regenerative mechanism of whole organisms.
Regeneration is a fascinating phenomenon. The fact that many organisms have the capacity to regenerate lost parts and even remake complete copies of themselves is difficult to fathom; so difficult, in fact, that for a very long time people were reluctant to believe regeneration actually took place. It seemed unbelievable that some organisms could re-grow lost limbs, organs, and other body parts. If only we could do the same! Unfortunately, our regenerative capacities are limited to hair, nails, and skin, while the liver and a few other tissues display more restricted regenerative abilities. What if we could grow back lost limbs, or damaged organs? This question has inspired many stories, dating back to Greek mythology, wherein Prometheus was doomed to regenerate his liver after it had been devoured by birds. Regeneration has permeated many imaginations; it has appeared in many literary and religious texts, and has also provoked much interest from the scientific community.
Alejandro Sánchez Alvarado's laboratory group has employed molecular tools to investigate old questions about regeneration and as a result have identified some of the molecular mechanisms determining polarity. Recent work by his group has shown Wnt-β-catenin signaling determines whether a tail or a head will form during regeneration in planarians. This study was motivated by work Thomas Hunt Morgan conducted in the late nineteenth century. Morgan observed that during regeneration a planarian cut into rather small pieces would sometimes regenerate a head at both its anterior and posterior end rather than a head and a tail. This led Morgan to think the size of the piece must affect the regenerative process.
Abraham Trembley's discovery of the remarkable regenerative capacity of the hydra caused many to question their beliefs about the generation of organisms. Born 3 September 1710 to a prominent Geneva family, Trembley studied at the Calvin Institute, now the University of Geneva, where he completed his thesis on calculus. He went on to become tutor for Count William Bentinck's two sons, and it was while teaching the boys natural history that Trembley came across a strange organism in a sample of pond water. This mysterious polyp, or hydra, had been previously described by Antoni van Leeuwenhoek, as well as an anonymous English gentleman in 1704, but Trembley was unaware of the polyp's identity and began a series of experiments to determine whether it was an animal or a plant. His investigations were also motivated by his observation that the number of arms on different polyps varied, an irregularity uncommon in animals. Yet Trembley felt that it was an animal.
Advanced Cell Technology, Inc. (ACT) is a biotechnology company that uses stem cell technology to develop novel therapies in the field of regenerative medicine. Formed in 1994, ACT grew from a small agricultural cloning research facility located in Worcester, Massachusetts, into a multi-locational corporation involved in using both human embryonic stem cells (hESC) and human adult stem cells as well as animal cells for therapeutic innovations. Through its work in developing alternative methods for hESC derivation and its public statements, ACT has also played an active role in stimulating and participating in public debate over stem cell research.
Lazzaro Spallanzani's imaginative application of experimental methods, mastery of microscopy, and wide interests led him to significant contributions in natural history, experimental biology, and physiology. His detailed and thoughtful observations illuminated a broad spectrum of problems ranging from regeneration to the genesis of thunderclouds.
The gradient theory is recognized as Charles Manning Child's most significant scientific contribution. Gradients brought together Child's interest in development and his fascination with the origins of individuality and organization. The gradient theory grew from his studies of regeneration, which were largely based on work he conducted with marine invertebrates, such as the ascidian flat worm, planaria and the hydroid, tubularia. Child observed that regeneration occurred in a graded process along the axis of the organism, with the characteristics of each physiological process seemingly determined by its location along the axis. To explain these observations, Child posited the existence of physiological factors working to guide the regenerative process. He was convinced that these differences along the gradients could be explained quantitatively.
Tissue engineering is a field of regenerative medicine that integrates the knowledge of scientists, physicians, and engineers into the construction or reconstruction of human tissue. Practitioners of tissue engineering seek to repair, replace, maintain, and enhance the abilities of a specific tissue or organ by means of living cells. More often than not stem cells are the form of living cells used in this technology. Tissue engineering is one of the disciplines involved in translating knowledge of developmental biology into the clinical setting. One focus that this field has taken is the understanding of tissue and organ development during embryogenesis, as this knowledge will open avenues to new applications of this technology.