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regeneration

 
American Heritage Dictionary:

re·gen·er·a·tion

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(rĭ-jĕn'ə-rā'shən) pronunciation
n.
  1. The act or process of regenerating or the state of being regenerated.
  2. Spiritual or moral revival or rebirth.
  3. Biology. Regrowth of lost or destroyed parts or organs.

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McGraw-Hill Science & Technology Encyclopedia:

Regeneration

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physiology
engineering

(physiology)

The process by which an animal restores a lost part of its body. Broadly defined, the term can include wound healing, tissue repair, and many kinds of restorative activities. Within the field of developmental biology, however, most research in regeneration involves systems in which removing a complex structure or major part of an organism initiates a chain of events that produces a structure that duplicates the missing part both functionally and anatomically.

The best-known and most widely studied examples of regeneration are those involving epimorphosis, in which the lost structure is reproduced directly by a combination of cell proliferation and redifferentiation of new tissue. Examples can be found throughout the animal kingdom. Research on regenerating systems yields information regarding basic mechanisms of animal development. Noteworthy has been the progress in understanding the factors that control pattern formation in the development of complex structures, such as vertebrate limbs.

Mammals, birds, and reptiles have a much more poorly developed ability than amphibians and fish to regenerate complete organs, but nevertheless can reform missing tissue and restore function after partial removal of certain organs. For example, if part of the liver is cut away, the remaining portions increase in size to compensate for the missing tissue and to restore the normal functional capacity of the organ. The process of liver regeneration involves the triggering of active growth in the remaining liver cells, in cells of bile ductules, and in unspecialized cells called stem cells, all of which are usually quiescent in the normal liver. Proliferation of these cells and their subsequent differentiation are key events in the process by which the missing liver mass is replaced and adequate hepatic function restored. In the musculoskeletal system, different populations of quiescent stem cells allow efficient replacement of damaged or partially removed bones and muscles. See also Bone; Liver; Muscle.

Of all vertebrates, amphibians have the most highly developed capacity for regeneration. Certain species have the ability to regenerate not only limbs and tails but also parts of the eye, lower jaw, intestine, and heart. Complete regeneration of amputated limbs can occur throughout the lifetime of most salamanders and newts. In frogs and toads, the ability to regenerate limbs is lost during metamorphosis to the adult form.

Protozoa and simple multicellular animals, including sponges, coelenterates, and flatworms, display remarkable capacities for regeneration following various experimental manipulations. Regenerative ability in such organisms correlates closely with their capacity to reproduce asexually, most commonly by fission or by budding, and the mechanisms of growth involved in regeneration are often very similar to those of asexual propagation. For example, just as complete ciliated protozoa will develop after fission, which divides the nucleus and organelles between daughter cells, intact individuals will also be reconstituted from fragments of a single organism if the fragment contains a complete set of the genetic material and a portion of the original cell's cortical cytoplasm. Similar rules regarding the importance of the nucleus apply to regenerative processes in all protozoa.

Most annelids, such as the earthworm, can readily regenerate segments after their removal: some species can regenerate whole organisms from any fragment. Like more primitive invertebrates, certain annelids can reproduce asexually by transverse fission. The capacities for fission and for reconstitution from fragments in annelids are remarkable, considering the anatomical complexity of animals in this phylum. When an earthworm is cut transversely into two parts, the anterior part can regenerate several posterior segments. The ability of the posterior half to regenerate anterior segments is, however, more limited and is absent altogether in some species. Experiments in which components of the nervous system are removed surgically have revealed the importance of a neural influence for segment regeneration, presumably mediated by a growth-stimulating hormone secreted from neural cells. See also Annelida.

The ability of certain echinoderms, such as starfish, to regenerate missing arms is well known. Cutting such an animal into several pieces results in each piece forming a new organism, a phenomenon that usually requires the presence of at least some of the central portion of the body. Equally remarkable is a regenerative response shown by another echinoderm, the sea cucumber. When this animal is strongly irritated, it eviscerates itself through its anus or through a rupture of its body wall. This phenomenon produces a nearly empty sack of skin and muscle, which then proceeds to regenerate all the internal organs, beginning with the digestive tract. See also Echinodermata.

The capacity for appendage regeneration is widespread among the many diverse members of the phylum Arthropoda. In these complex animals with well-developed exoskeletons and no asexual mode of reproduction, regeneration shows a close correlation with the molting process. See also Arthropoda; Developmental biology.

Regeneration (engineering)

The process of feeding back a portion of the output signal of an amplifier to its input in such a way that the input signal is reinforced. The result is greatly increased amplification. The feedback must be positive; that is, the two signals must be in phase, and it must be limited in magnitude to prevent the circuit from going into oscillation. See also Feedback circuit.

Roget's Thesaurus:

regeneration

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noun

    A fundamental change in one's beliefs: conversion, metanoia, rebirth. See change/persist.

Oxford Dictionary of Architecture & Landscaping:

regeneration

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The securing of the repair and conservation of older structures to ensure their future viability.

Oxford Dictionary of Sports Science & Medicine:

regeneration

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Replacement of destroyed tissue by proliferation of the same kind of cells. Compare fibrosis.

Oxford Dictionary of Biochemistry:

regeneration

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  1. (in chemistry) the process of restoring to a state of preparedness for use, as in the case of an ion-exchange resin washed with acid or alkali to restore it to the H+ or OH− form.
  2. (in biology) the growth of new tissues or organs to replace ones lost or damaged, e.g. through injury or surgery. In some tissues, such as liver, epithelial tissue, or pancreas, regeneration occurs by simple duplication of cells, with the regeneration time varying from one week to a year. In other systems, such as epidermis, renewal is from specialized stem cells. Regenerating liver can be used as a model in which systems involved in proliferation are more highly activated than in normal liver. It is a unique property of liver that it is possible to remove two thirds of the organ yet it regenerates to form an organ of similar total weight to the original, albeit with somewhat different organization of the lobes. Many plants can regenerate a complete plant from a shoot segment or a single leaf or from tissue culture cells.

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Saunders Veterinary Dictionary:

regeneration

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The natural renewal of a structure, as of a lost tissue or part.

Mosby's Dental Dictionary:

regeneration

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(rē-jen′ər-ā′shən)
n

The renewal or repair of lost tissue or parts.

Random House Word Menu:

categories related to 'regeneration'

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Random House Word Menu by Stephen Glazier
For a list of words related to regeneration, see:
  • Reproduction and Development - regeneration: regrowth of lost parts of organ or organism, as in worms
  • New Age - regeneration: spiritual renewal or rebirth, esp. a radical transformation of one’s life

Wikipedia on Answers.com:

Regeneration (biology)

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Sun flower sea star regenerates its arms
Dwarf yellow-headed gecko with regenerating tail

In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans.[1][2] At its most elementary level, regeneration is mediated by the molecular processes of DNA synthesis.[3][4] Regeneration in biology, however, mainly refers to the morphogenic processes that characterizes the phenotypic plasticity of traits allowing multi-cellular organisms to repair and maintain the integrity of their physiological and morphological states. Above the genetic level, regeneration is fundamentally regulated by asexual cellular processes.[5] It is important to note that regeneration is different from reproduction. For example, hydra performs regeneration but it reproduces by the method of budding.

The hydra and the planarian flatworm have long served as model organisms for their highly adaptive regenerative capabilities.[6] Once wounded, their cells become activated and start to remodel tissues and organs back to the pre-existing state.[7] The Caudata ("urodeles"; salamanders and newts), an order of tailed amphibians, is possibly the most adept vertebrate group at regeneration, given their capability of regenerating limbs, tails, jaws, eyes and a variety of internal structures.[1] The regeneration of organs is a common and widespread adaptive capability among metazoan creatures.[6] In a related context, some animals are able to reproduce asexually through fragmentation, budding, or fission.[5] A planarian parent, for example, will constrict, split in the middle, and each half generates a new end to form two clones of the original.[8] Echinoderms (such as the starfish), crayfish, many reptiles, and amphibians exhibit remarkable examples of tissue regeneration. The case of autotomy, for example, serves as a defensive function as the animal detaches a limb or tail to avoid capture. After the limb or tail has been autotomized, cells move into action and tissues regenerate.[9][10][11] Ecosystems are regenerative as well. Following a disturbance, such as a fire or pest outbreak in a forest, pioneering species will occupy, compete for space, and establish themselves in the newly opened habitat. The new growth of seedlings and community assembly process is known as regeneration in ecology.[12][13]

Contents

Cellular molecular fundamentals

Pattern formation in the morphogenesis of an animal is regulated by genetic induction factors that put cells to work after damage has occurred. Neural cells, for example, express growth-associated proteins, such as GAP-43, tubulin, actin, an array of novel neuroptides, and cytokines that induce a cellular physiological response to regenerate from the damage.[14] Many of the genes that are involved in the original development of tissues are reinitialized during the regenerative process. Cells in the primordia of zebrafish fins, for example, express four genes from the homeobox msx family during development and regeneration.[15]

Tissues and organs

"Regenerative strategies include the rearrangement of pre-existing tissue, the use of adult somatic stem cells and the dedifferentiation and/or transdifferentiation of cells, and more than one mode can operate in different tissues of the same animal. All these strategies result in the re-establishment of appropriate tissue polarity, structure and form."[16]:873 During the developmental process genes are activated that serve to modify the properties of cell as they differentiate into different tissues. Development and regeneration involves the coordination and organization of populations cells into a blastema, which is "a mound of stem cells from which regeneration begins."[17] Dedifferentiation of cells means that they lose their tissue-specific characteristics as tissues remodel during the regeneration process. Transdifferentiation of cells is when they lose their tissue-specific characteristics during the regeneration process, and then re-differentiate to a different kind of cell.[16]

Model organisms in Bilateria

Planaria (Platyhelminthes)

Planaria exhibit an extraordinary ability to regenerate lost body parts. For example, a planarian split lengthwise or crosswise will regenerate into two separate individuals. In one experiment, T. H. Morgan found that a piece corresponding to 1⁄279th of a planarian could successfully regenerate into a new worm. This size (about 10,000 cells) is typically accepted as the smallest fragment that can regrow into a new planarian. Regeneration of planaria is epimorphic regeneration. After amputation, stump cells form blastema.

Vertebrates

Amphibians

Simple animals like planarians have an enhanced capacity to regenerate because the adults retain clusters of stem cells (neoblast) within their bodies which migrate to the parts that need healing. They then divide and differentiate to grow the missing tissue and organs back. The process is more complex in vertebrates, but nevetheless, salamanders possess strong powers of regeneration, which begins immediately after amputation. Limb regeneration in the axolotl and newt has been extensively studied.

Limb regeneration in newts occurs in two major steps, first dedifferentiation of adult cells into a stem cell state similar to embryonic cells and second, development of these cells into new tissue more or less the same way it developed the first time.[18]

After amputation, the epidermis migrates to cover the stump in less than 12 hours, forming a structure called the apical epidermal cap (AEC). Over the next several days there are changes in the underlying stump tissues that result in the formation of a blastema (a mass of dedifferentiated proliferating cells). As the blastema forms, pattern formation genes – such as HoxA and HoxD – are activated as they were when the limb was formed in the embryo.[19][20] The distal tip of the limb (the autopod, which is the hand or foot) is formed first in the blastema. The intermediate portions of the pattern are filled in during growth of the blastema by the process of intercalation.[18][19] Motor neurons, muscle, and blood vessels grow with the regenerated limb, and reestablish the connections that were present prior to amputation. The time that this entire process takes varies according to the age of the animal, ranging from about a month to around three months in the adult and then the limb becomes fully functional.

In spite of the historically few researchers studying limb regeneration, remarkable progress has been made recently in establishing the neotenous amphibian the axolotl (Ambystoma mexicanum) as a model genetic organism. This progress has been facilitated by advances in genomics, bioinformatics, and somatic cell transgenesis in other fields, that have created the opportunity to investigate the mechanisms of important biological properties, such as limb regeneration, in the axolotl.[21] The Ambystoma Genetic Stock Center (AGSC) is a self-sustaining, breeding colony of the axolotl supported by the National Science Foundation as a Living Stock Collection. Located at the University of Kentucky, the AGSC is dedicated to supplying genetically well-characterized axolotl embryos, larvae, and adults to laboratories throughout the United States and abroad. An NIH-funded NCRR grant has led to the establishment of the Ambystoma EST database, the Salamander Genome Project (SGP) that has led to the creation of the first amphibian gene map and several annotated molecular data bases, and the creation of the research community web portal.[22]

Mice

The mechanism for regeneration in Murphy Roths Large (MRL) mice has been found, and is related to the deactivation of the p21 gene.[23][24]

Adult mammals have limited regenerative capacity compared to most vertebrate embryos/larvae, adult salamanders and fish. The MRL mouse is a strain of mouse that exhibits remarkable regenerative abilities for a mammal. Study of the regenerative process in these animals is aimed at discovering how to duplicate them in humans.

By comparing the differential gene expression of scarless healing MRL mice and a poorly-healing C57BL/6 mouse strain, 36 genes have been identified that are good candidates for studying how the healing process differs in MRL mice and other mice.[25][26]

The regenerative ability of MRL mice does not, however, protect them against myocardial infarction; heart regeneration in adult mammals (neocardiogenesis) is limited, because heart muscle cells are nearly all terminally differentiated. MRL mice show the same amount of cardiac injury and scar formation as normal mice after a heart attack.[27] However, recent studies provide evidence that this may not always be the case, and that MRL mice can regenerate after heart damage. [1]

Humans

Fingers

In May 1932, L.H. McKim published a report in The Canadian Medical Association Journal, that described the regeneration of an adult digit-tip following amputation. A house surgeon in the Montreal General Hospital underwent amputation of the distal phalanx to stop the spread of an infection. In less than one month following surgery, x-ray analysis showed the regrowth of bone while macroscopic observation showed the regrowth of nail and skin.[28] This is one of the earliest recorded examples of adult human digit-tip regeneration.[29]

Studies in the 1970s showed that children up to the age of 10 or so who lose fingertips in accidents can regrow the tip of the digit within a month provided their wounds are not sealed up with flaps of skin – the de facto treatment in such emergencies. They normally won't have a finger print, and if there is any piece of the finger nail left it will grow back as well, usually in a square shape rather than round. [30][31]

In August 2005, Lee Spievack, then in his early sixties, accidentally sliced off the tip of his right middle finger just above the first phalanx. His brother, Dr. Alan Spievack, was researching regeneration and provided him with powdered extracellular matrix, developed by Dr. Stephen Badylak of the McGowan Institute of Regenerative Medicine. Mr. Spievack covered the wound with the powder, and the tip of his finger re-grew in four weeks.[32] The news was released in 2007. Lee Spievack is the first documented case of an adult human regenerating fingertips;[30] however, Ben Goldacre has described this as "the missing finger that never was", claiming that fingertips regrow and quoted Simon Kay, professor of hand surgery at the University of Leeds, who from the picture provided by Goldacre described the case as seemingly "an ordinary fingertip injury with quite unremarkable healing"[33]

A similar story was reported by CNN. A woman named Deepa Kulkarni lost the tip of her little finger and was initially told by doctors that nothing could be done. Her personal research and consultation with several specialists including Badylak eventually resulted in her undergoing regenerative therapy and regaining her fingertip.[34]

Ribs

There have appeared claims that human ribs could regenerate if the periosteum, the membrane surrounding the rib, were left intact. In one study rib material was used for skull reconstruction and all 12 patients had complete regeneration of the resected rib.[35]

Liver

The human liver is one of the few glands in the body that has the ability to regenerate from as little as 25% of its tissue.[36] This is largely due to the unipotency of hepatocytes.[37] Resection of liver can induce the proliferation of the remained hepatocytes until the lost mass is restored, where the intensity of the liver’s response is directly proportional to the mass resected. For almost 80 years surgical resection of the liver in rodents has been a very useful model to the study of cell proliferation.[38][39]

Kidney

Regenerative capacity of the kidney remains largely unexplored. The basic functional and structural unit of the kidney is nephron, which is mainly composed of four components: the glomerulus, tubules, the collecting duct and peritubular capillaries. The regenerative capacity of the mammalian kidney is limited compared to that of lower vertebrates.

In the mammalian kidney, the regeneration of the tubular component following an acute injury is well known. Recently regeneration of the glomerulus has also been documented. Following an acute injury, the proximal tubule is damaged more, and the injured epithelial cells slough off the basement membrane of the nephron. The surviving epithelial cells, however, undergo migration, dedifferentiation, proliferation, and redifferentiation to replenish the epithelial lining of the proximal tubule after injury. Recently, the presence and participation of kidney stem cells in the tubular regeneration has been shown. However, the concept of kidney stem cells is currently emerging. In addition to the surviving tubular epithelial cells and kidney stem cells, the bone marrow stem cells have also been shown to participate in regeneration of the proximal tubule, however, the mechanisms remain controversial. Recently, studies examining the capacity of bone marrow stem cells to differentiate into renal cells are emerging.[40]

Like other organs, the kidney is also known to regenerate completely in lower vertebrates such as fish. Some of the known fish that show remarkable capacity of kidney regeneration are goldfish, skates, rays, and sharks. In these fish, the entire nephron regenerates following injury or partial removal of the kidney.

Heart

Several animals can regenerate heart damage, but in mammals cardiomyocytes (heart muscle cells) cannot proliferate (multiply) and heart damage causes scarring and fibrosis.

The long held view was that mammalian cardiomyocytes are terminally differentiated and cannot divide. However inhibition of p38 MAP kinase was found to induce mitosis in adult mammalian cardiomyocytes.[41] Treatment with FGF1 and p38 MAP kinase inhibitors regenerates the heart, reduces scarring, and improves cardiac function in rats with cardiac injury.[42]

Notes

  1. ^ a b Carlson, B. M. (2007). Principles of Regenerative Biology. Elsevier Inc.. pp. 400. ISBN 978-0-12-369439-3. http://www.sciencedirect.com/science/book/9780123694393. 
  2. ^ Gabor, M. H.; Hotchkiss, R. D. (1979). "Parameters governing bacterial regeneration and genetic recombination after fusion of Bacillus subtilis protoplasts". Journal of Bacteriology 137 (3): 1346–1353. PMC 218319. PMID 108246. http://jb.asm.org/cgi/content/abstract/137/3/1346. 
  3. ^ Himeno, Y.; Engelman, R. W.; Good, R. A. (1992). "Influence of calorie restriction on oncogene expression and DNA synthesis during liver regeneration". Proceedings of the National Academy of Sciences of the United States of America 89 (12): 5497–5501. doi:10.1073/pnas.89.12.5497. PMC 49319. PMID 1608960. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49319. 
  4. ^ Bryant, P. J.; Fraser, S. E. (1988). "Wound healing, cell communication, and DNA synthesis during imaginal disc regeneration in Drosophila". Developmental Biology 127 (1): 197–208. doi:10.1016/0012-1606(88)90201-1. PMID 2452103. http://linkinghub.elsevier.com/retrieve/pii/0012160688902011. 
  5. ^ a b Brokes, J. P.; Kumar, A.. "Comparative Aspects of Animal Regeneration". Annu. Rev. Cell Dev. Biol. 28: 525–549. doi:10.1146/annurev.cellbio.24.110707.175336?select23=Choose. http://www.annualreviews.org/doi/full/10.1146/annurev.cellbio.24.110707.175336?select23=Choose. 
  6. ^ a b Sánchez, A. A. (2000). "Regeneration in the metazoans: why does it happen?". Bioessays 22 (6): 578–590. doi:10.1002/(SICI)1521-1878(200006)22:6<578::AID-BIES11>3.0.CO;2-#. PMID 10842312. http://planaria.neuro.utah.edu/publications/BioEssays.pdf. 
  7. ^ Reddien, P. W.; Alvarado, A. S. (2004). "Fundamentals of planarian regenerations". Annual Review of Cell and Developmental Biology 20: 725–757. doi:10.1146/annurev.cellbio.20.010403.095114. PMID 15473858. http://www.annualreviews.org/doi/abs/10.1146/annurev.cellbio.20.010403.095114. 
  8. ^ Campbell, N. A.. Biology (4th ed.). California: The Benjamin Cummings Publishing Company, Inc.. pp. 1206. 
  9. ^ Wilkie, I. (2001). "Autotomy as a prelude to regeneration in echinoderms". Microscopy Research and Technique 55 (6): 369–396. doi:10.1002/jemt.1185. PMID 11782069. 
  10. ^ Maiorana, V. C. (1977). "Tail autotomy, functional conflicts and their resolution by a salamander". Nature 2265 (5594): 533–535. doi:10.1038/265533a0. 
  11. ^ Maginnis, T. L. (2006). "The costs of autotomy and regeneration in animals: a review and framework for future research". Behavioural Ecology 7 (5): 857–872. doi:10.1093/beheco/arl010. http://beheco.oxfordjournals.org/content/17/5/857.full. 
  12. ^ Dietze, M. C.; Clark, J. S. (2008). "Changing the gap dynamics paradigm: Vegetative regenerative control on forest response to disturbance". Ecological Monographs 78 (3): 331–347. doi:10.1890/07-0271.1. http://coweeta.uga.edu/publications/10300.pdf. 
  13. ^ Bailey, J. D.; Covington, W. W. (2002). "Evaluation ponderosa pine regeneration rates following ecological restoration treatments in northern Arizona, USA". Forest Ecology and Management 155: 271–278. doi:10.1016/S0378-1127(01)00564-3. http://library.eri.nau.edu/gsdl/collect/erilibra/index/assoc/HASH0e9a.dir/doc.pdf. 
  14. ^ Fu, S. Y.; Gordon, T. (1997). "The cellular and molecular basis of peripheral nerve regeneration". Molecular Neurobiology 14 (1–2): 67–116. doi:10.1007/BF02740621. PMID 9170101. http://www.springerlink.com/content/675770336wq42078/. 
  15. ^ Akimenko, M.; Johnson, S. L.; Wseterfield, M.; Ekker, M. (1996). "Differential induction of four msx homeobox genes during fin development and regeneration in zebrafish". Development 121 (2): 347–357. PMID 7768177. http://dev.biologists.org/content/121/2/347.full.pdf. 
  16. ^ a b Alvarado, A. S.; Tsonis, P. A. (2006). "Bridging the regeneration gap: genetic insights from diverse animal models". Nat. Rev. Genet. 7 (11): 873–884. doi:10.1038/nrg1923. PMID 17047686. http://planaria.neuro.utah.edu/publications/NRG2006.pdf. 
  17. ^ Kumar, A.; Godwin, J. W.; Gates, P. B.; Garza-Garcia, A. A.; Brokes, J. P. (2007). "Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate". Science 318 (5851): 772–7. doi:10.1126/science.1147710. PMC 2696928. PMID 17975060. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2696928. 
  18. ^ a b Odelberg SJ (August 2004). "Unraveling the Molecular Basis for Regenerative Cellular Plasticity". PLoS Biology 2 (8): E232. doi:10.1371/journal.pbio.0020232. PMC 509298. PMID 15314652. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=509298. 
  19. ^ a b Bryant SV, Endo T, Gardiner DM (2002). "Vertebrate limb regeneration and the origin of limb stem cells". The International journal of developmental biology 46 (7): 887–96. PMID 12455626. 
  20. ^ Mullen LM, Bryant SV, Torok MA, Blumberg B, Gardiner DM (November 1996). "Nerve dependency of regeneration: the role of Distal-less and FGF signaling in amphibian limb regeneration". Development (Cambridge, England) 122 (11): 3487–97. PMID 8951064. 
  21. ^ Endo T, Bryant SV, Gardiner DM (June 2004). "A stepwise model system for limb regeneration". Developmental Biology 270 (1): 135–45. doi:10.1016/j.ydbio.2004.02.016. PMID 15136146. 
  22. ^ http://www.ambystoma.org
  23. ^ Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang X-M, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E (March 2010). "Lack of p21 expression links cell cycle control and appendage regeneration in mice". Proceedings of the National Academy of Sciences 107 (11): 5845–50. doi:10.1073/pnas.1000830107. PMC 2851923. PMID 20231440. http://www.pnas.org/content/early/2010/03/08/1000830107.abstract. Lay summary – PhysOrg.com. 
  24. ^ Humans Could Regenerate Tissue Like Newts By Switching Off a Single Gene
  25. ^ Masinde G, Li X, Baylink DJ, Nguyen B, Mohan S (April 2005). "Isolation of wound healing/regeneration genes using restrictive fragment differential display-PCR in MRL/MPJ and C57BL/6 mice". Biochemical and Biophysical Research Communications 330 (1): 117–22. doi:10.1016/j.bbrc.2005.02.143. PMID 15781240. 
  26. ^ Mansuo L. Hayashi, B. S. Shankaranarayana Rao, Jin-Soo Seo, Han-Saem Choi, Bridget M. Dolan, Se-Young Choi, Sumantra Chattarji, and Susumu Tonegawa (2007 July). "Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice". Proceedings of the National Academy of Sciences 104 (27): 11489–94. doi:10.1073/pnas.0705003104. PMC 1899186. PMID 17592139. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1899186. 
  27. ^ Abdullah I, Lepore JJ, Epstein JA, Parmacek MS, Gruber PJ (2005 Mar-April). "MRL mice fail to heal the heart in response to ischemia-reperfusion injury". Wound Repair Regen 13 (2): 205–208. doi:10.1111/j.1067-1927.2005.130212.x. PMID 15828946. 
  28. ^ McKim, L.H. (May 1932). "REGENERATION OF THE DISTAL PHALANX". The Canadian Medical Association Journal 26 (5): 549–550. PMC 402335. PMID 20318716. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=402335. 
  29. ^ Wicker, Jordan; Kenneth Kamler (August 2009). "Current concepts in limb regeneration: A hand surgeon's perspective". Annals of the New York Academy of Sciences 1172 (1): 95–109. doi:10.1111/j.1749-6632.2009.04413.x. PMID 19735243. 
  30. ^ a b Weintraub, Arlene (MAY 24, 2004). "The Geniuses Of Regeneration". BusinessWeek. http://www.businessweek.com/magazine/content/04_21/b3884008_mz001.htm. 
  31. ^ Illingworth Cynthia M (1974). "Trapped fingers and amputated fingertips in children.". J. Ped. Surgery 9: 853–858. 
  32. ^ "Regeneration recipe: Pinch of pig, cell of lizard". Associated Press. MSNBC. February 19, 2007. http://www.msnbc.msn.com/id/17171083/. Retrieved October 24, 2008. 
  33. ^ Goldacre, Ben (May 3, 2008). "The missing finger that never was". The Guardian. http://www.guardian.co.uk/science/2008/may/03/medicalresearch.health. 
  34. ^ Woman's persistence pays off in regenerated fingertip by Elizabeth Cohen. CNN website, September 9, 2010 4:51 p.m., page found 2010-09-16.
  35. ^ Munro IR, Guyuron B (November 1981). "Split-Rib Cranioplasty". Annals of Plastic Surgery 7 (5): 341–346. doi:10.1097/00000637-198111000-00001. PMID 7332200. 
  36. ^ "Liver Regeneration Unplugged". Bio-Medicine. 2007-04-17. http://www.bio-medicine.org/medicine-news/Liver-Regeneration-Unplugged-19988-1/. Retrieved 2007-04-17. 
  37. ^ Michael, Dr. Sandra Rose (2007). "Bio-Scalar Technology: Regeneration and Optimization of the Body-Mind Homeostasis" (PDF). 15th Annual AAAAM Conference: 2. http://eesystem.com/docs/AAAAM%202007%20long%20biography%20abstr_.pdf. Retrieved October 24, 2008. 
  38. ^ Higgins, GM and RM Anderson RM (1931). "Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal". Arch. Pathol. 12: 186–202. 
  39. ^ Michalopoulos, GK and MC DeFrances (April 4, 1997). "Liver regeneration". Science 276 (5309): 60–66. doi:10.1126/science.276.5309.60. PMID 9082986. 
  40. ^ Kurinji Singaravelu et al.(July 2009). "In Vitro Differentiation of MSC into Cells with a Renal Tubular Epithelial-Like Phenotype". Renal Failure 31(6):492-502. http://www.informaworld.com/smpp/content~content=a913452182~db=all~jumptype=rss
  41. ^ http://genesdev.cshlp.org/content/19/10/1175.full
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Sources

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  2. Nye HL, Cameron JA, Chernoff EA, Stocum DL (February 2003). "Regeneration of the urodele limb: a review". Dev. Dyn. 226 (2): 280–94. doi:10.1002/dvdy.10236. PMID 12557206. 
  3. Yu H, Mohan S, Masinde GL, Baylink DJ (December 2005). "Mapping the dominant wound healing and soft tissue regeneration QTL in MRL x CAST". Mamm. Genome 16 (12): 918–24. doi:10.1007/s00335-005-0077-0. PMID 16341671. 
  4. Gardiner DM, Blumberg B, Komine Y, Bryant SV (June 1995). "Regulation of HoxA expression in developing and regenerating axolotl limbs". Development 121 (6): 1731–41. PMID 7600989. 
  5. Torok MA, Gardiner DM, Shubin NH, Bryant SV (August 1998). "Expression of HoxD genes in developing and regenerating axolotl limbs". Dev. Biol. 200 (2): 225–33. doi:10.1006/dbio.1998.8956. PMID 9705229. 
  6. Putta S, Smith JJ, Walker JA, et al. (August 2004). "From biomedicine to natural history research: EST resources for ambystomatid salamanders". BMC Genomics 5 (1): 54. doi:10.1186/1471-2164-5-54. PMC 509418. PMID 15310388. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=509418. 
  7. Andrews, Wyatt (March 23, 2008). "Medicine's Cutting Edge: Re-Growing Organs". Sunday Morning (CBS News). http://www.cbsnews.com/stories/2008/03/22/sunday/main3960219.shtml. 

External links
Embryology
Other
Metamorphosis · Regeneration · Ageing · Model organisms · Compartment · Metamerism

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