Regeneration (biology)

Source: Wikipedia, the free encyclopedia.
Sunflower sea star regenerates its arms.
Dwarf yellow-headed gecko with regenerating tail

Regeneration in

resilient to natural fluctuations or events that cause disturbance or damage.[1] Every species is capable of regeneration, from bacteria to humans.[2][3][4] Regeneration can either be complete[5] where the new tissue is the same as the lost tissue,[5] or incomplete[6] after which the necrotic tissue becomes fibrotic.[6]

At its most elementary level, regeneration is mediated by the molecular processes of

cell differentiation.[7][8] Regeneration in biology, however, mainly refers to the morphogenic processes that characterize 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.[9] Regeneration is different from reproduction. For example, hydra perform regeneration but reproduce by the method of budding
.

The regenerative process occurs in two multi-step phases: the preparation phase and the redevelopment phase.

skin cells
again become skin cells and muscle cells become muscles. These de-differentiated cells divide until enough cells are available at which point they differentiate again and the shape of the blastema begins to flatten out. It is at this point that the second phase begins, the redevelopment of the limb. In this stage, genes signal to the cells to differentiate themselves and the various parts of the limb are developed. The end result is a limb that looks and operates identically to the one that was lost, usually without any visual indication that the limb is newly generated.

The hydra and the

metazoan creatures.[12] In a related context, some animals are able to reproduce asexually through fragmentation, budding, or fission.[9] 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.[14]

Echinoderms (such as the sea star), 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 the tissues will regenerate.[15][16][17] In some cases a shed limb can itself regenerate a new individual.[18] Limited regeneration of limbs occurs in most fishes and salamanders, and tail regeneration takes place in larval frogs and toads (but not adults). The whole limb of a salamander or a triton will grow repeatedly after amputation. In reptiles, chelonians, crocodilians and snakes are unable to regenerate lost parts, but many (not all) kinds of lizards, geckos and iguanas possess regeneration capacity in a high degree. Usually, it involves dropping a section of their tail and regenerating it as part of a defense mechanism. While escaping a predator, if the predator catches the tail, it will disconnect.[19]

Ecosystems

Main article: Regeneration (ecology)

Ecosystems can be regenerative. 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.[20][21]

Cellular molecular fundamentals

Pattern formation in the morphogenesis of an animal is regulated by

cytokines that induce a cellular physiological response to regenerate from the damage.[22] 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.[23]

Tissues

"Strategies include the rearrangement of pre-existing tissue, the use of adult

stem cells and the dedifferentiation and/or transdifferentiation of cells, and more than one mode can operate in different tissues of the same animal.[1] All these strategies result in the re-establishment of appropriate tissue polarity, structure and form."[24]: 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".[25] Dedifferentiation of cells means that they lose their tissue-specific characteristics as tissues remodel during the regeneration process. This should not be confused with the transdifferentiation of cells which is when they lose their tissue-specific characteristics during the regeneration process, and then re-differentiate to a different kind of cell.[24]

In animals

Arthropods

Limb regeneration

Many arthropods can regenerate limbs and other appendages following either injury or autotomy.[26] Regeneration capacity is constrained by the developmental stage and ability to molt.

Crustaceans, which continually molt, can regenerate throughout their lifetimes.[27] While molting cycles are generally hormonally regulated, limb amputation induces premature molting.[26][28]

Hemimetabolous insects such as crickets can regenerate limbs as nymphs, before their final molt.[29]

Holometabolous insects can regenerate appendages as larvae prior to the final molt and metamorphosis. Beetle larvae, for example, can regenerate amputated limbs. Fruit fly larvae do not have limbs but can regenerate their appendage primordia, imaginal discs.[30] In both systems, the regrowth of the new tissue delays pupation.[30][31]

Mechanisms underlying appendage limb regeneration in insects and crustaceans are highly conserved.[32] During limb regeneration species in both taxa form a blastema that proliferates and grows to repattern the missing tissue.[33]

Venom regeneration

Arachnids, including scorpions, are known to regenerate their venom, although the content of the regenerated venom is different from the original venom during its regeneration, as the venom volume is replaced before the active proteins are all replenished.[34]

Fruit fly model

The fruit fly Drosophila melanogaster is a useful model organism to understand the molecular mechanisms that control regeneration, especially gut and germline regeneration.[30] In these tissues, resident stem cells continually renew lost cells.[30] The Hippo signaling pathway was discovered in flies and was found to be required for midgut regeneration. Later, this conserved signaling pathway was also found to be essential for regeneration of many mammalian tissues, including heart, liver, skin, and lung, and intestine.[35]

Annelids

Many

oligochaetes, where head regeneration has been lost three separate times.[39]

Along with epimorphosis, some

oligochaetes
is currently not well understood. Although relatively under-reported, it is possible that morphallaxis is a common mode of inter-segment regeneration in annelids. Following regeneration in L. variegatus, past posterior segments sometimes become anterior in the new body orientation, consistent with morphallaxis.

Following amputation, most annelids are capable of sealing their body via rapid muscular contraction. Constriction of body muscle can lead to infection prevention. In certain species, such as Limnodrilus, autolysis can be seen within hours after amputation in the ectoderm and mesoderm. Amputation is also thought to cause a large migration of cells to the injury site, and these form a wound plug.

Echinoderms

Tissue regeneration is widespread among echinoderms and has been well documented in starfish (Asteroidea), sea cucumbers (Holothuroidea), and sea urchins (Echinoidea). Appendage regeneration in echinoderms has been studied since at least the 19th century.[41] In addition to appendages, some species can regenerate internal organs and parts of their central nervous system.[42] In response to injury starfish can autotomize damaged appendages. Autotomy is the self-amputation of a body part, usually an appendage.  Depending on severity, starfish will then go through a four-week process where the appendage will be regenerated.[43] Some species must retain mouth cells to regenerate an appendage, due to the need for energy.[44] The first organs to regenerate, in all species documented to date, are associated with the digestive tract. Thus, most knowledge about visceral regeneration in holothurians concerns this system.[45]

Planaria (Platyhelminthes)

Regeneration research using Planarians began in the late 1800s and was popularized by T.H. Morgan at the beginning of the 20th century.[44] Alejandro Sanchez-Alvarado and Philip Newmark transformed planarians into a model genetic organism in the beginning of the 20th century to study the molecular mechanisms underlying regeneration in these animals.[46] Planarians 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[44] or a fragment with as few as 10,000 cells can successfully regenerate into a new worm within one to two weeks.[47] After amputation, stump cells form a blastema formed from neoblasts, pluripotent cells found throughout the planarian body.[48] New tissue grows from neoblasts with neoblasts comprising between 20 and 30% of all planarian cells.[47] Recent work has confirmed that neoblasts are totipotent since one single neoblast can regenerate an entire irradiated animal that has been rendered incapable of regeneration.[49] In order to prevent starvation a planarian will use their own cells for energy, this phenomenon is known as de-growth.[13]

Amphibians

Limb regeneration in the

cell differentiation and tissue growth using similar genetic mechanisms that deployed during embryonic development.[54] Ultimately, blastemal cells will generate all the cells for the new structure.[51]

Axolotls can regenerate a variety of structures, including their limbs.

After amputation, the epidermis migrates to cover the stump in 1–2 hours, forming a structure called the wound epithelium (WE).

Ambystoma mexicanum, an organism with exceptional limb regenerative capabilities, likely undergoes epigenetic alterations in its blastema cells that enhance expression of genes involved in limb regeneration. The Axolotl has very little blood and has an excess of epidermal cells. This allows the affected area to then flourish with epidermal cells and continued gene expression allows the area to regenerate to its natural being.[61]

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

transgenesis in other fields, that have created the opportunity to investigate the mechanisms of important biological properties, such as limb regeneration, in the axolotl.[54] 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.[62] In 2022, a first spatiotemporal map revealed key insights about axolotl brain regeneration, also providing the interactive Axolotl Regenerative Telencephalon Interpretation via Spatiotemporal Transcriptomic Atlas.[63][64]

Frog model

Anurans (frogs) can only regenerate their limbs during embryonic development.[65] Reactive oxygen species (ROS) appear to be required for a regeneration response in the anuran larvae.[66] ROS production is essential to activate the Wnt signaling pathway, which has been associated with regeneration in other systems.[66]

Once the limb skeleton has developed in frogs, regeneration does not occur (Xenopus can grow a cartilaginous spike after amputation).

BDNF, growth hormone, resolvin D5, and retinoic acid), in a single dose lasting 24 hours, was shown to trigger long-term leg regeneration in adult X. laevis. Instead of a single spike, a paddle-shaped growth is obtained at the end of the limb by 18 months.[67]

Hydra

epithelial cells that is isolated from the body has the ability to regenerate into a smaller version of itself.[68] The high proportion of stem cells in the hydra supports its efficient regenerative ability.[69]

Regeneration among hydra occurs as foot regeneration arising from the basal part of the body, and head regeneration, arising from the apical region.[68] Regeneration tissues that are cut from the gastric region contain polarity, which allows them to distinguish between regenerating a head in the apical end and a foot in the basal end so that both regions are present in the newly regenerated organism.[68] Head regeneration requires complex reconstruction of the area, while foot regeneration is much simpler, similar to tissue repair.[70] In both foot and head regeneration, however, there are two distinct molecular cascades that occur once the tissue is wounded: early injury response and a subsequent, signal-driven pathway of the regenerating tissue that leads to cellular differentiation.[69] This early-injury response includes epithelial cell stretching for wound closure, the migration of interstitial progenitors towards the wound, cell death, phagocytosis of cell debris, and reconstruction of the extracellular matrix.[69]

Regeneration in hydra has been defined as morphallaxis, the process where regeneration results from remodeling of existing material without cellular proliferation.[71][72] If a hydra is cut into two pieces, the remaining severed sections form two fully functional and independent hydra, approximately the same size as the two smaller severed sections.[68] This occurs through the exchange and rearrangement of soft tissues without the formation of new material.[69]

During Hydra head regeneration there are coordinated gene expression and chromatin regulation changes.[73] An enhancer is a short DNA sequence (50–1500 base pairs) that can be bound by transcription factors to increase the transcription of a particular gene. In the enhancer regions that are activated during head regeneration, a set of transcription factor motifs commonly occur that appear to facilitate coordinated gene expression.[73]

Aves (birds)

Owing to a limited literature on the subject, birds are believed to have very limited regenerative abilities as adults. Some studies[74] on roosters have suggested that birds can adequately regenerate some parts of the limbs and depending on the conditions in which regeneration takes place, such as age of the animal, the inter-relationship of the injured tissue with other muscles, and the type of operation, can involve complete regeneration of some musculoskeletal structure. Werber and Goldschmidt (1909) found that the goose and duck were capable of regenerating their beaks after partial amputation[74] and Sidorova (1962) observed liver regeneration via hypertrophy in roosters.[75] Birds are also capable of regenerating the hair cells in their cochlea following noise damage or ototoxic drug damage.[76] Despite this evidence, contemporary studies suggest reparative regeneration in avian species is limited to periods during embryonic development. An array of molecular biology techniques have been successful in manipulating cellular pathways known to contribute to spontaneous regeneration in chick embryos.[77] For instance, removing a portion of the elbow joint in a chick embryo via window excision or slice excision and comparing joint tissue specific markers and cartilage markers showed that window excision allowed 10 out of 20 limbs to regenerate and expressed joint genes similarly to a developing embryo. In contrast, slice excision did not allow the joint to regenerate due to the fusion of the skeletal elements seen by an expression of cartilage markers.[78]

Similar to the physiological regeneration of hair in mammals, birds can regenerate their feathers in order to repair damaged feathers or to attract mates with their plumage. Typically, seasonal changes that are associated with breeding seasons will prompt a hormonal signal for birds to begin regenerating feathers. This has been experimentally induced using thyroid hormones in the Rhode Island Red Fowls.[79]

Mammals

Spiny mice (Acomys cahirinus pictured here) can regenerate skin, cartilage, nerves and muscle.

Mammals are capable of cellular and physiological regeneration, but have generally poor reparative regenerative ability across the group.

sweat glands, fur and cartilage.[84] In addition to these two species, subsequent studies demonstrated that Acomys cahirinus could regenerate skin and excised tissue in the ear pinna.[85][86]

Despite these examples, it is generally accepted that adult mammals have limited regenerative capacity compared to most vertebrate embryos/larvae, adult salamanders and fish.[87] But the regeneration therapy approach of Robert O. Becker, using electrical stimulation, has shown promising results for rats[88] and mammals in general.[89]

Some researchers have also claimed that the MRL mouse strain exhibits enhanced regenerative abilities. Work comparing the differential gene expression of scarless healing MRL mice and a poorly-healing C57BL/6 mouse strain, identified 36 genes differentiating the healing process between MRL mice and other mice.[90][91] Study of the regenerative process in these animals is aimed at discovering how to duplicate them in humans, such as deactivation of the p21 gene.[92][93] However, recent work has shown that MRL mice actually close small ear holes with scar tissue, rather than regeneration as originally claimed.[85]

MRL mice are not protected 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.[94] However, recent studies provide evidence that this may not always be the case, and that MRL mice can regenerate after heart damage.[95]

Humans

Main article: Regeneration in humans
See also: Tissue engineering

The regrowth of lost tissues or organs in the human body is being researched. Some tissues such as skin regrow quite readily; others have been thought to have little or no capacity for regeneration, but ongoing research suggests that there is some hope for a variety of tissues and organs.[1][96] Human organs that have been regenerated include the bladder, vagina and the penis.[97]

As are all

metazoans, humans are capable of physiological regeneration (i.e. the replacement of cells during homeostatic maintenance that does not necessitate injury). For example, the regeneration of red blood cells via erythropoiesis occurs through the maturation of erythrocytes from hematopoietic stem cells in the bone marrow, their subsequent circulation for around 90 days in the blood stream, and their eventual cell-death in the spleen.[98] Another example of physiological regeneration is the sloughing and rebuilding of a functional endometrium during each menstrual cycle in females in response to varying levels of circulating estrogen and progesterone.[99]

However, humans are limited in their capacity for reparative regeneration, which occurs in response to injury. One of the most studied regenerative responses in humans is the hypertrophy of the liver following liver injury.[100][101] For example, the original mass of the liver is re-established in direct proportion to the amount of liver removed following partial hepatectomy,[102] which indicates that signals from the body regulate liver mass precisely, both positively and negatively, until the desired mass is reached. This response is considered cellular regeneration (a form of compensatory hypertrophy) where the function and mass of the liver is regenerated through the proliferation of existing mature hepatic cells (mainly hepatocytes), but the exact morphology of the liver is not regained.[101] This process is driven by growth factor and cytokine regulated pathways.[100] The normal sequence of inflammation and regeneration does not function accurately in cancer. Specifically, cytokine stimulation of cells leads to expression of genes that change cellular functions and suppress the immune response.[103]

Adult neurogenesis is also a form of cellular regeneration. For example, hippocampal neuron renewal occurs in normal adult humans at an annual turnover rate of 1.75% of neurons.

myocardium following infarction, proliferation is only found in around 1% of myocytes around the area of injury, which is not enough to restore function of cardiac muscle
. However, this may be an important target for regenerative medicine as it implies that regeneration of cardiomyocytes, and consequently of myocardium, can be induced.

Another example of reparative regeneration in humans is fingertip regeneration, which occurs after phalange amputation distal to the nail bed (especially in children)[107][108] and rib regeneration, which occurs following osteotomy for scoliosis treatment (though usually regeneration is only partial and may take up to one year).[109]

Yet another example of regeneration in humans is vas deferens regeneration, which occurs after a vasectomy and which results in vasectomy failure.[110]

Reptiles

The ability and degree of regeneration in reptiles differs among the various species (see

snakes, but see.[111] Lizards possess the highest regenerative capacity as a group.[113][114][117] Following autotomous tail loss, epimorphic regeneration of a new tail proceeds through a blastema-mediated process that results in a functionally and morphologically similar structure.[112][113]

Chondrichthyes

It has been estimated that the average shark loses about 30,000 to 40,000 teeth in a lifetime. Leopard sharks routinely replace their teeth every 9–12 days and this is an example of physiological regeneration. This can occur because shark teeth are not attached to a bone, but instead are developed within a bony cavity.[74]

Rhodopsin regeneration has been studied in skates and rays. After complete photo-bleaching, rhodopsin can completely regenerate within 2 hours in the retina.[118]

White bamboo sharks can regenerate at least two-thirds of their liver and this has been linked to three micro RNAs, xtr-miR-125b, fru-miR-204, and has-miR-142-3p_R-. In one study, two-thirds of the liver was removed and within 24 hours more than half of the liver had undergone hypertrophy.[119]

Some sharks can regenerate scales and even skin following damage. Within two weeks of skin wounding, mucus is secreted into the wound and this initiates the healing process. One study showed that the majority of the wounded area was regenerated within 4 months, but the regenerated area also showed a high degree of variability.[120]

See also

Notes

  1. ^
    PMID 23517218
    .
  2. ^
    ISBN 978-0-12-369439-3
    .
  3. PMID 108246
    .
  4. PMID 35359300
  5. ^ a b Min S, Wang SW, Orr W (2006). "Graphic general pathology: 2.2 complete regeneration". Pathology. pathol.med.stu.edu.cn. Archived from the original on 2012-12-07. Retrieved 2012-12-07. (1) Complete regeneration: The new tissue is the same as the tissue that was lost. After the repair process has been completed, the structure and function of the injured tissue are completely normal
  6. ^ a b Min S, Wang SW, Orr W (2006). "Graphic general pathology: 2.3 Incomplete regeneration". Pathology. pathol.med.stu.edu.cn. Archived from the original on 2013-11-10. Retrieved 2012-12-07. The new tissue is not the same as the tissue that was lost. After the repair process has been completed, there is a loss in the structure or function of the injured tissue. In this type of repair, it is common that granulation tissue (stromal connective tissue) proliferates to fill the defect created by the necrotic cells. The necrotic cells are then replaced by scar tissue.
  7. PMID 1608960
    .
  8. PMID 2452103
    .
  9. ^
    PMID 18598212
    .
  10. ^
    S2CID 231963500
    .
  11. ISSN 2296-701X
    .
  12. ^
    PMID 10842312. Archived from the original
    (PDF) on 2013-11-11. Retrieved 2010-12-15.
  13. ^
    S2CID 1320382
    .
  14. ISBN 978-0-8053-1940-8
    .
  15. S2CID 20291486
    .
  16. S2CID 4219251
    .
  17. doi:10.1093/beheco/arl010
    .
  18. ^ Edmondson, C. H. (1935). "Autotomy and regeneration of Hawaiian starfishes" (PDF). Bishop Museum Occasional Papers. 11 (8): 3–20.
  19. ^ "UCSB Science Line". scienceline.ucsb.edu. Retrieved 2015-11-02.
  20. doi:10.1890/07-0271.1. Archived from the original
    (PDF) on 2010-06-10. Retrieved 2010-12-15.
  21. doi:10.1016/S0378-1127(01)00564-3. Archived from the original
    (PDF) on 2013-11-11. Retrieved 2011-06-25.
  22. S2CID 13045638
    .
  23. PMID 7768177
    .
  24. ^
    S2CID 2978615. Archived from the original
    (PDF) on 2013-11-10. Retrieved 2010-12-16.
  25. PMID 17975060
    .
  26. ^
    ISBN 978-0-323-13922-9
    .
  27. ^
    S2CID 22877405
    .
  28. JSTOR 1538400
    .
  29. PMID 35337452
    , retrieved 2022-06-08
  30. ^
    PMID 32253254
    .
  31. ^ Roche, John P. (September 22, 2020). "Limb Regeneration in Lady Beetles: Product of Selection or Developmental Byproduct?". Entomology Today. Entomological Society of America. Retrieved September 23, 2020.
  32. PMID 26296354
    .
  33. PMID 26253405
    .
  34. PMID 17344080
    .
  35. PMID 27592171
    .
  36. ^
    PMID 21672762
    .
  37. PMID 4655324
    .
  38. PMID 21545709
    .
  39. ^
    ISBN 978-0-470-01590-2
    .
  40. PMID 25122930
    .
  41. S2CID 23560812
    .
  42. PMID 19126208
    .
  43. PMID 11171408
    .
  44. ^
    S2CID 33712732
    .
  45. S2CID 11533400
    .
  46. S2CID 8085897
    .
  47. ^
    PMID 4853459
    .
  48. PMID 23799578
    .
  49. PMID 21566185
    .
  50. ^
    doi:10.1080/24750263.2021.1943549
  51. ^
    PMID 11523827
    .
  52. S2CID 21409289
    .
  53. S2CID 3946430
    .
  54. ^
    S2CID 7581434
    .
  55. PMID 22537500
    .
  56. S2CID 29415248
    .
  57. ^
    PMID 12455626
    .
  58. PMID 8951064
    .
  59. ^ Souppouris, Aaron (May 23, 2013). "Scientists identify cell that could hold the secret to limb regeneration". The Verge. Macrophages are a type of repairing cell that devour dead cells and pathogens, and trigger other immune cells to respond to pathogens.
  60. PMID 23690624
    .
  61. ^ Min S, Whited JL. Limb blastema formation: How much do we know at a genetic and epigenetic level? J Biol Chem. 2023 Feb;299(2):102858. doi: 10.1016/j.jbc.2022.102858. Epub 2022 Dec 31. PMID 36596359; PMCID: PMC9898764
  62. ^ Voss SR, Muzinic L, Zimmerman G (2018). "Sal-Site". Ambystoma.org.
  63. ^ "Single-cell Stereo-seq reveals new insights into axolotl brain regeneration". News-Medical.net. 6 September 2022. Retrieved 19 October 2022.
  64. S2CID 252010604
    .
  65. ^
    S2CID 49315283
    .
  66. ^
    S2CID 3645313
    .
  67. PMID 35080969
    .
  68. ^
    PMID 17234176
    .
  69. ^
    PMID 25086685
    .
  70. PMID 24703763
    .
  71. ^ Morgan TH (1901). Regeneration. Columbia University Biological Series. Vol. 7. New York: The MacMillan Company.
  72. S2CID 29433846
    .
  73. ^ a b Murad R, Macias-Muñoz A, Wong A, Ma X, Mortazavi A. Coordinated Gene Expression and Chromatin Regulation during Hydra Head Regeneration. Genome Biol Evol. 2021 Dec 1;13(12):evab221. doi: 10.1093/gbe/evab221. PMID 34877597; PMCID: PMC8651858
  74. ^ a b c Vorontsova MA, Liosner LD (1960). Billet F (ed.). Asexual Reproduction and Regeneration. Translated by Allen PM. London: Pergamon Press. pp. 367–371.
  75. S2CID 39410595
    .
  76. S2CID 25619337
    .
  77. PMID 18773459
    .
  78. PMID 23036343
    .
  79. doi:10.1242/jeb.13.3.344
    .
  80. PMID 16369608
    .
  81. PMID 24383056
    .
  82. PMID 15293809
    .
  83. PMID 21145316
    .
  84. PMID 23018966
    .
  85. ^
    PMID 27109826
    .
  86. PMID 27499879
    .
  87. ^ Xu K (July 2013). "Humans' Ability To Regenerate Damaged Organs Is At Our Fingertips". Business Insider.
  88. S2CID 4209650
    .
  89. PMID 4503923
    .
  90. PMID 15781240
    .
  91. PMID 17592139
    .
  92. PMID 20231440
    .
  93. ^ Humans Could Regenerate Tissue Like Newts By Switching Off a Single Gene
  94. S2CID 7360046
    .
  95. ^ "Regeneration in the mammalian heart demonstrated by Wistar researchers | EurekAlert! Science News". Eurekalert.org. Retrieved 2019-03-16.
  96. ^ Min S, Wang SW, Orr W (2006). "Graphic general pathology: 2.2 complete regeneration". Pathology. pathol.med.stu.edu.cn. Archived from the original on 2012-12-07. Retrieved 2013-11-10. After the repair process has been completed, the structure and function of the injured tissue are completely normal. This type of regeneration is common in physiological situations. Examples of physiological regeneration are the continual replacement of cells of the skin and repair of the endometrium after menstruation. Complete regeneration can occur in pathological situations in tissues that have good regenerative capacity.
  97. ^ Mohammadi D (4 October 2014). "Bioengineered organs: The story so far…". The Guardian. Retrieved 9 March 2015.
  98. ISBN 978-0-12-369439-3
    .
  99. PMID 434029
    .
  100. ^
    S2CID 2756510
    .
  101. ^
    S2CID 30647609
    .
  102. S2CID 34148354
    .
  103. PMID 28884042
    .
  104. PMID 23746839
    .
  105. PMID 19342590
    .
  106. PMID 11396441
    .
  107. PMID 20318716
    .
  108. PMID 19067422
    .
  109. PMID 16047208
    .
  110. ^ Korin Miller (September 11, 2017). "Here's What Happens When a Vasectomy Fails". SELF. Retrieved 2019-03-16.
  111. ^
    PMID 34564085
    .
  112. ^
    PMID 20334040
    .
  113. ^
    PMID 21846350
    .
  114. ^ a b Bellairs A, Bryant S (1985). "Autonomy and Regeneration in Reptiles". In Gans C, Billet F (eds.). Biology of the Reptilia. Vol. 15. New York: John Wiley and Sons. pp. 301–410.
  115. JSTOR 1563441
    .
  116. S2CID 1079753
    .
  117. ^ Vickaryous M (2014). "Vickaryous Lab: Regeneration - Evolution - Development". Department of Biomedical Sciences, University of Guelph.
  118. PMID 1478278
    .
  119. PMID 24151623
    .
  120. S2CID 29300907
    .

Sources

Further reading

External links

Wikiquote has quotations related to Regeneration (biology).
Wikisource has the text of the 1911 Encyclopædia Britannica article "Regeneration of Lost Parts".
Retrieved from "https://en.wikipedia.org/w/index.php?title=Regeneration_(biology)&oldid=1220345110"