Author
David L. Stocum
Other affiliations: University of Indianapolis, Indiana University, University of Illinois at Urbana–Champaign
Bio: David L. Stocum is an academic researcher from Indiana University – Purdue University Indianapolis. The author has contributed to research in topics: Regeneration (biology) & Blastema. The author has an hindex of 38, co-authored 116 publications receiving 4057 citations. Previous affiliations of David L. Stocum include University of Indianapolis & Indiana University.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: This article reviews studies on blastema cell proliferation and proposes a model of blastemal self‐organization and patterning based on local cell interactions that intercalate positional identities within circumferential and proximodistal boundaries that outline the regenerate.
Abstract: Urodele amphibians have been widely used for studies of limb regeneration. In this article, we review studies on blastema cell proliferation and propose a model of blastemal self-organization and patterning. The model is based on local cell interactions that intercalate positional identities within circumferential and proximodistal boundaries that outline the regenerate. The positional identities created by the intercalation process appear to be reflected in the molecular composition of the cell surface. Transcription factors and signaling molecules involved in patterning are discussed within the context of the boundary/intercalation model.
204 citations
•
11 Sep 2006TL;DR: There is substantial evidence that non-regenerating mammalian tissues harbor regeneration-competent cells that are forced into a pathway of scar tissue formation, and Regenerative medicine uses three approaches.
Abstract: 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.
183 citations
••
TL;DR: The effects of varying doses of retinoic acid on forelimb regeneration in larval Ambystoma mexicanum and adult Notophthalmus viridescens amputated through the basal carpals were compared, and the regenerating limbs were maximally sensitive to the retinoid during the period of dedifferentiation and accumulation of blastema cells.
150 citations
••
TL;DR: Results indicate that positional memory in regenerating limbs is directly related to blastema cell affinity, and that very similar or identical sets of level-specific affinity properties are shared by forelimb and hindlimb cells.
Abstract: An assay that detects position-related differences in affinity of axolotl regeneration blastema cells in vivo was used to test whether retinoic acid, which proximalizes regenerate pattern, simultaneously proximalizes blastema cell affinity. The assay involved autografting or homografting late bud forelimb blastomas derived from the wrist, elbow or midupper arm levels to the dorsal surface of the blastema-stump junction of an ipsilateral, medium-bud-stage hindlimb regenerating from the midthigh level. The grafted blastemas consistently displaced to their corresponding levels on the proximodistal axis of the host regenerate, indicating the existence of level-specific differences in blastema cell affinity. Retinoic acid proximalized the pattern of donor forelimb regenerates to the level of the girdle and abolished their displacement behaviour on untreated host hindlimbs. Conversely, untreated forelimb donor blastemas displaced distally to their corresponding levels on host ankle regenerates, that had been proximalized to the level of the girdle by retinoic acid. These results indicate that positional memory in regenerating limbs is directly related to blastema cell affinity, and that very similar or identical sets of level-specific affinity properties are shared by forelimb and hindlimb cells.
132 citations
••
TL;DR: In vitro experiments suggest that changes in mesenchymal positional value in response to discontinuity can be interpreted in terms of gradients of cell-cell adhesivity, and they focus attention on the importance of molecular studies of blastema cell surfaces for future understanding of regeneration and morphogenesis in general.
132 citations
Cited by
More filters
••
TL;DR: Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.
Abstract: New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.
4,288 citations
••
TL;DR: Current evidence suggests that in vivo such unexpected transformations of adult somatic stem cells are exceedingly rare and in some cases can be accounted for by equally unexpected alternative explanations.
1,249 citations
••
TL;DR: The identification and isolation of stem cells from a number of tissues provides appropriate targets for prospective gene therapies and has the potential to significantly alter the perspective of tissue engineering.
Abstract: The concept of producing 'spare parts' of the body for replacement of damaged or lost organs lies at the core of the varied biotechnological practices referred to generally as tissue engineering. Use of postnatal stem cells has the potential to significantly alter the perspective of tissue engineering. Successful long-term restoration of continuously self-renewing tissues such as skin, for example, depends on the use of extensively self-renewing stem cells. The identification and isolation of stem cells from a number of tissues provides appropriate targets for prospective gene therapies.
988 citations
••
TL;DR: How cell adhesions interact with nanotopography is discussed, and insight is provided as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled.
Abstract: Stem cells respond to nanoscale surface features, with changes in cell growth and differentiation mediated by alterations in cell adhesion. The interaction of nanotopographical features with integrin receptors in the cells' focal adhesions alters how the cells adhere to materials surfaces, and defines cell fate through changes in both cell biochemistry and cell morphology. In this Review, we discuss how cell adhesions interact with nanotopography, and we provide insight as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled. We expect knowledge gained from the study of cell-nanotopography interactions to accelerate the development of next-generation stem cell culture materials and implant interfaces, and to fuel discovery of stem cell therapeutics to support regenerative therapies.
879 citations
••
TL;DR: The model is described, which can explain regulative behavior in cockroach legs, the imaginal disks of Drosophila, and regenerating and developing amphibian limbs, and suggests that it may have general applicability to epimorphic fields.
Abstract: We have described a formal model for pattern regulation in epimorphic fields in which positional information is specified in terms of polar coordinates in two dimensions. We propose that cells within epimorphic fields behave according to two simple rules, the shortest intercalation rule and the complete circle rule, for both of which there is direct experimental evidence. It is possible to understand a large number of different behaviors of epimorphic fields as a straight-forward consequence of these two rules, and the model therefore provides a context in which to view many of the results of experimental embryology. Although we have confined our discussion to cockroach legs, the imaginal disks of Drosophila, and regenerating and developing amphibian limbs, the fact that the model can explain regulative behavior in such evolutionarily diverse animals suggests that it may have general applicability to epimorphic fields. The predictions which the model makes should make it possible to assess its applicability to other developing systems, and to investigate the cellular mechanisms involved.
844 citations