Regenerative biology and medicine

The replacement of damaged tissues and organs with tissue and organ transplants or bionic 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-regenerating tissues. Regeneration is accomplished by three mechanisms, each of which uses or produces a different kind of regeneration-competent 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 progenitor cells 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 is invariably 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 produce a 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 inhibited and the appropriate signaling environment is supplied. An overview of regenerative mechanisms, approaches of regenerative medicine, research directions, and research issues will be given.     

Regenerative medicine in China: new advances and hopes

正Tissue and organ repair as well as regeneration are globalfrontiers in the field of stem cell research and regenerativemedicine. Regenerative medicine is closely associated withtreatments of almost all human diseases, injuries, and ag-ing-related problems. The rapid advancements in stem celltechnology, tissue engineering, and physical as well aschemical interventions have resulted in significant progressin tissue and organ repair as well as regeneration. Currently,a single tissue type can be repaired and regenerated throughcell transplantation, trophic factors, biodegradable scaffolds,     

Regenerative medicine research in China: from basic research to clinical practice

<正>I am very happy to write editorial for this Special Issue of Stem Cells and Regenerative Medicine in China in Science China Life Sciences.As we all know,stem cells and regenerative medicine research is the frontiers not only in China,but also in the world.In recent decades,rapid research progressing,strong governmental support and recruitment of highly trained scientists from abroad together with domestic outstanding researchers and clinicians have made it possible     

Regenerative medicine in multiple sclerosis: identifying pharmacological targets of adult neural stem cell differentiation

Progressive axonal loss from chronic demyelination in multiple sclerosis (MS) is the key contributor to clinical decline. Failure to regenerate myelin by adult oligodendrocyte precursor cells (OPCs), a widely distributed neural stem cell population in the adult brain, is one of the major causes of axonal degeneration. In order to develop successful therapies to protect the integrity of axons in MS, it is important to identify and understand the key molecular pathways involved in myelin regeneration (remyelination) by adult OPCs. This review highlights recent findings on the critical signaling pathways associated with OPC differentiation following CNS demyelination. We discuss the role of LINGO-1, Notch, Wnt, and retinoid X receptor (RXR) signaling, and how they might be useful pharmacological targets to overcoming remyelination failure in MS.     

Regenerative medicine: Evidence for remarkable healing power of adult (somatic) stem cells

There is a little doubt that regenerative medicine primarily based on stem cell-derived therapies would revolutionize health care and prevent thousands, perhaps, millions of human deaths. However, human society is sharply fragmented by the real and imaginary boundaries of social, ethical, political and religious views on how to reach the promise lend of future benefits of regenerative medicine. This sharp division to a large degree is arising from the concept that desired therapeutic gains would not be possible to achieve without exploiting unique healing potentials of embryonic stem cells. The paper published in this issue of Cell Cycle reports experimental findings which seem to challenge this broadly held view¹. Robert Hoffman and colleagues describe the proof of principle experiments in mice demonstrating a remarkable healing power of a cell line which was derived from pluripotent adult (somatic) stem cells and maintained in culture for the extended period of time. The paper represents a logical continuation of the multi-year effort of this team and would be recognized as a breakthrough if these unique and truly fascinating findings will be independently replicated and their relevance will be validated for human conditions. I would like to express one general note of caution that should be exercised when considerations are given for therapeutic applications of stem cells. Growing body of evidence supports the concept that stem cells are the seeds of the most clinically deadly form of therapy-resistant human cancers arising in different organs and rapidly spreading across the human body^2-5. Therefore, potential therapeutic benefits of stem cells should be carefully measured and weighted against the possible side effects for every patient and each disease indication. Our decision making process in disease management should continue to be firmly adhered to the conservative principles of the evidence-based medicine. However, there are circumstances, one example of which is illustrated by this paper¹, when medical and humanitarian necessities would override these concerns. Even the prospect of developing deadly cancer in the future should not stop us from helping human beings who are deprived of the ability to walk, move, or speak.

References

Amoh Y, Li L, Katsuoka K, Hoffman RM. Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function. Cell Cycle 2008: 7: In this issue.Glinsky GV. Death-from-cancer signatures and stem cell contribution to metastatic cancer. Cell Cycle 2005; 4: 1171-5.Glinsky GV, Glinskii AB, Berezovskaya O. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 2005; 115:1503-21.Glinsky GV. Stem cell origin of death-from-cancer phenotypes of human prostate and breast cancers. Stem Cells Reviews 2007; 3:79-93.Glinsky, GV. “Stemness” genomics law governs clinical behavior of human cancer: Implications for decision making in disease management. J Clin Oncol 2008; In press.     

Regenerative medicine in Parkinson's disease: generation of mesencephalic dopaminergic cells from embryonic stem cells

Cell replacement therapy has been proposed as a means of replacing specific populations of cells lost through trauma, disease or ageing. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of midbrain dopaminergic neurons. Intrastriatal transplants of human foetal mesencephalic tissue in Parkinson's patients have demonstrated clinical efficacy, but the limited availability of tissue precludes systematic use of this treatment. Human embryonic stem cells are capable of unlimited self-renewal and can differentiate into cells representative of all three germ layers, including cells of the central nervous system. These cells may thus provide a relatively unlimited source of cells for transplantation, if appropriate differentiation protocols to generate highly enriched and specific populations of neural cells can be developed.     

Regenerative medicine for diseases of the head and neck: principles of in vivo regeneration

The application of endogenous regeneration in regenerative medicine is based on the concept of inducing regeneration of damaged or lost tissues from residual tissues in situ. Therefore, endogenous regeneration is also termed in vivo regeneration as opposed to mechanisms of ex vivo regeneration which are applied, for example, in the field of tissue engineering. The basic science foundation for mechanisms of endogenous regeneration is provided by the field of regenerative biology. The ambitious vision for the application of endogenous regeneration in regenerative medicine is stimulated by investigations in the model organisms of regenerative biology, most notably hydra, planarians and urodeles. These model organisms demonstrate remarkable regenerative capabilities, which appear to be conserved over large phylogenetical stretches with convincing evidence for a homologue origin of an endogenous regenerative capability. Although the elucidation of the molecular and cellular mechanisms of these endogenous regenerative phenomena is still in its beginning, there are indications that these processes have potential to become useful for human benefit. Such indications also exist for particular applications in diseases of the head and neck region. As such epimorphic regeneration without blastema formation may be relevant to regeneration of sensorineural epithelia of the inner ear or the olphactory epithelium. Complex tissue lesions of the head and neck as they occur after trauma or tumor resections may be approached on the basis of relevant mechanisms in epimorphic regeneration with blastema formation.     

Regenerative medicine: Clinical relevance,implications, and limitations of the stem cell-based therapies

Many believe that success of the concept of regenerative medicine critically depends on our unlimited access to the human embryonic stem cells for scientific and therapeutic applications. Recent ground-breaking studies seem to challenge this broadly held view by demonstrating a remarkable healing power of mammalian adult (somatic) stem cells. However, mounting evidence of involvement of stemness pathways in development of therapy-resistant metastatic cancers argue for more careful considerations of potential risk and benefits associated with the stem cell-based therapies.