The urodele limb regeneration blastema

Stocum, David L.

doi:10.1111/j.1432-0436.1984.tb01403.x

Cited by 118 publications

(35 citation statements)

References 73 publications

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“…The polarity of regenerates formed by axially reversed early blastemas conformed to that of the host limb stump, whereas older blastemas formed regenerates that maintained their original polarity. These results suggested that the early blastema had no developmental capacity (was “nullipotent”) and that appendage type, position of origin, and axial polarity were determined by signals from adjacent stump tissue (Stocum, 1984, for a review).…”

Section: Blastema Patterning: Autonomous or Induced?mentioning

confidence: 99%

“…Grafted blastema mesenchyme forced to dedifferentiate when re‐covered by wound epidermis, as when several mesenchymes are massed and grafted to the back (De Both, 1970; Polezhaev, 1937), or when proximal halves of stylopodial forelimb blastemas are grafted to the ankle stump of the hindlimb (Stocum & Melton, 1977), developed according to origin. The mass of cells in these experiments is greater than that of an accumulation blastema and thus cell interactions may be a factor in whether or not the positional identity of individual blastema cells can be expressed (Stocum, 1984), although it should be noted that small clusters of prospective autopodial blastema cells failed to become incorporated into stylopodial tissue when transplanted into the prospective stylopodium of the blastema and instead sorted into the autopodial region (Echeverri & Tanaka, 2005). Pellets of posterior blastema cells cultured in vitro can induce supernumerary structures after implanting them to the anterior side of a blastema, but lose the capacity to do so after a week in culture (Groell, Gardiner, & Bryant, 1993).…”

Section: Blastema Patterning: Autonomous or Induced?mentioning

confidence: 99%

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Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

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109

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This review explores the historical and current state of our knowledge about urodele limb regeneration. Topics discussed are (1) blastema formation by the proteolytic histolysis of limb tissues to release resident stem cells and mononucleate cells that undergo dedifferentiation, cell cycle entry and accumulation under the apical epidermal cap. (2) The origin, phenotypic memory, and positional memory of blastema cells. (3) The role played by macrophages in the early events of regeneration. (4) The role of neural and AEC factors and interaction between blastema cells in mitosis and distalization. (5) Models of pattern formation based on the results of axial reversal experiments, experiments on the regeneration of half and double half limbs, and experiments using retinoic acid to alter positional identity of blastema cells. (6) Possible mechanisms of distalization during normal and intercalary regeneration. (7) Is pattern formation is a self‐organizing property of the blastema or dictated by chemical signals from adjacent tissues? (8) What is the future for regenerating a human limb?

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Section: Blastema Patterning: Autonomous or Induced?mentioning

confidence: 99%

Section: Blastema Patterning: Autonomous or Induced?mentioning

confidence: 99%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

Self Cite

109

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“…The limb blastema, as illustrated in Fig. 2A, is a selforganizing system that is independent of any templating or inductive activities from the limb stump (18). The significance of this property can be illustrated by contrasting different strategies for the repair of a bone lesion resulting in a gap.…”

Section: Autonomy Of the Blastemamentioning

confidence: 99%

“…Such cues include limb identity, and indeed when regenerative cells are transplanted between different tissue contexts in the salamander, they retain their original identity (18,22). The regenerative territories for forelimb, hindlimb, and tail identity have been mapped by inserting a peripheral nerve branch into the vicinity of a superficial wound at different locations on the body and observing the identity of the resulting appendage (23).…”

Section: Autonomy Of the Blastemamentioning

confidence: 99%

Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine

Brockes

Kumar

2005

Science

345

280

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The regeneration of complex structures in adult salamanders depends on mechanisms that offer pointers for regenerative medicine. These include the plasticity of differentiated cells and the retention in regenerative cells of local cues such as positional identity. Limb regeneration proceeds by the local formation of a blastema, a growth zone of mesenchymal stem cells on the stump. The blastema can regenerate autonomously as a self-organizing system over variable linear dimensions. Here we consider the prospects for limb regeneration in mammals from this viewpoint.T he goal of regenerative medicine is to restore cells, tissues, and structures that are lost or damaged after disease, injury, or aging. The current approaches are influenced by our understanding of embryonic development, of tissue turnover and replacement in adult animals (1-3), and by tissue engineering and stem cell biology (4). The regeneration of organs and appendages after injury occurs in diverse animal groups and provides another important viewpoint, in addition to the demonstration that complex adult tissues can be rebuilt. The lessons of biological regeneration have not been extensively assimilated, in part because this attribute appears remote and exceptional from a mammalian perspective. This Review is concerned principally with lessons from regeneration in salamanders, the species of adult vertebrates that possesses the most extensive abilities (5, 6). We identify three properties of regeneration in salamandersautonomy, scaling, and plasticity-and discuss some of the cellular and molecular mechanisms underlying them. It may be desirable to implement these properties in the context of mammalian regeneration.Regenerative medicine currently uses three approaches ( Fig. 1) (4): the implantation of stem cells to build new structures, the implantation of cells pre-primed to develop in a given direction, and the stimulation of endogenous cells to replace missing structures. Each of the different aspects identified in the first two examples-the generation of an appropriate cohort of regenerative cells, their regulated division and differentiation, and the restoration of the appropriate part of the structure-must be evoked from endogenous cells in the third approach. These processes operate in adult animals that regenerate, and in addition, the regenerative response must be initiated by signals responsive to tissue injury or removal. One candidate signal in salamanders is the local activation of thrombin, a regulator of hemostasis and other aspects of the response to injury, as well as an activator of S phase (the phase of chromosome replication) reentry in differentiated cells (7-9).A salamander can regenerate its limbs and tail, upper and lower jaws, ocular tissues such as the lens and retina, the intestine, and small sections of the heart (10-13). The various contexts for regeneration do not present an equivalent degree of difficulty. To restore the intricate and discontinuous pattern of the vertebrate limb is a different proposition from replac...

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“…5 Wound healing through regeneration is seen ancestrally in more primitive organisms (eg, amphibians). 6 Interestingly, this type of wound healing has also been reported in early gestation in mammalian fetuses and in adult rabbits. 4,7 For instance, in humans, early in gestation, fetal wounds heal rapidly with minimal inflammation and complete regeneration of epithelial and mesenchymal tissues.…”

mentioning

confidence: 99%

Myometrial Wound Healing Post-Cesarean Delivery in the MRL/MpJ Mouse Model of Uterine Scarring

Buhimschi

Zhao

Sora

et al. 2010

The American Journal of Pathology

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There is little known about healing of the uterus after Cesarean delivery (CD). Uterine wound repair was studied by using two strains of mice with different wound healing characteristics: MRL/MpJ؉/؉ (MRL: "high-healer" phenotype) and C57Bl/6 ("low-healer" phenotype). First, we examined the morphology and histology of the uterine wall repair. We identified wound granulation tissue 3 days post-CD in both strains, albeit less in the MRL strain. Macroscopically, no scar could be identified either in MRL or C57Bl/6 mice on day 60 post-CD. However, histologically, we found significant differences in wound integration, inflammation, and collagen birefringence between the two strains of mice. Using a histological index, we provided evidence for significant differences in mitotic activity in the initial phases of uterine healing among strains. Functional behavior of the uterine scar also was analyzed by using biomechanical parameters such as slope (measure of stiffness), yield point (measure of elasticity), and break point (measure of strength). There were significant differences in stiffness of the scarred myometrium between the two phenotypes. MRL mice displayed a significantly lower yield point compared with C57Bl/6. The break point was reached faster on days 15 and 60 in both C57Bl/6 and MRL strains compared with day 3 post-CD. Our findings indicate that differences in regenerative ability translate in histological , mitotic , and functional differences in biomechanical properties of the scarred myometrium after CD.

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The urodele limb regeneration blastema

Cited by 118 publications

References 73 publications

Mechanisms of urodele limb regeneration

Mechanisms of urodele limb regeneration

Appendage Regeneration in Adult Vertebrates and Implications for Regenerative Medicine

Myometrial Wound Healing Post-Cesarean Delivery in the MRL/MpJ Mouse Model of Uterine Scarring

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