Regenerative biology and medicine
Department of Biology and Center for Regenerative Biology and Medicine School of Science Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA
Abstract The replacement of damaged tissues and organs with tissue and organ transplants orbionic implants has serious drawbacks. There is now emerging a new approach to tissue and organ replacement, regenerative biology and medicine. Regenerative biology seeks to understand the cellular and molecular differences between regenerating and non-regenerating tissues. Regenerative medicine seeks to apply this understanding to restore tissue structure and function in damaged, non-regeneratingtissues. Regeneration is accomplished by three mechanisms, each of which uses or produces a different kind of regenerationcompetent cell. Compensatory hyperplasia is regeneration by the proliferation of cells which maintain all or most of their differentiated functions (e.g., liver). The urodele amphibians regenerate a variety of tissues by the dedifferentiation of mature cells to produce progenitorcells capable of division. Many tissues contain reserve stem or progenitor cells that are activated by injury to restore the tissue while simultaneously renewing themselves. All regeneration-competent cells have two features in common. First, they are not terminally differentiated and can re-enter the cell cycle in response to signals in the injury environment. Second, their activation isinvariably accompanied by the dissolution of the extracellular matrix (ECM) surrounding the cells, suggesting that the ECM is an important regulator of their state of differentiation. Regenerative medicine uses three approaches. First is the transplantation of cells into the damaged area. Second is the construction of bioartificial tissues by seeding cells into a biodegradable scaffold where they producea normal matrix. Third is the use of a biomaterial scaffold or drug delivery system to stimulate regeneration in vivo from regeneration-competent cells. There is substantial evidence that non-regenerating mammalian tissues harbor regeneration-competent cells that are forced into a pathway of scar tissue formation. Regeneration can be induced if the factors leading to scar formation are inhibitedand the appropriate signaling environment is supplied. An overview of regenerative mechanisms, approaches of regenerative medicine, research directions, and research issues will be given. Keywords: Compensatory Hyperplasia, Dedifferentiation, Stem Cells, Regenerative Biology, Regenerative Medicine
The cost of tissue damage and loss due to degenerative disease and injury is enormous in terms ofhealth care dollars, lost economic productivity, diminished quality of life, and premature death. We are able to regenerate some tissues, such as blood, blood vessels, epithelia, liver, bone, muscle, and fingertips, but many others, such as spinal cord, heart muscle, and pancreas respond to injury by the formation of scar tissue. Tissues like bone and muscle, even though they regenerate afterfracture or tearing, cannot regenerate across a large gap. Two clinical approaches now used to replace damaged or failing
Corresponding author: David L. Stocum, Department of Biology and Center for Regenerative Biology and Medicine School of Science Indiana UniversityPurdue University at Indianapolis, Indianapolis, IN 46202, USA. E-mail: email@example.com Accepted 15 July 2001 270
organs andtissues are organ transplantation and implantation of bionic devices. Donor shortages and the side effects of required immunosuppression are drawbacks of the former, while use of the latter is limited by our inability to engineer and manufacture artificial tissues and organs that duplicate the durability, strength, form, function, and biocompatibility of natural tissues. In the 21st century, however,...