Content deleted Content added
→History of human tissue: What has been proven, the fact humans create scar tissue? Lol. Asking for clarification |
m Dating maintenance tags: {{Cn}} |
||
| (17 intermediate revisions by 6 users not shown) | |||
Line 7:
==History of human tissue==
In humans with non-injured tissues, the tissue naturally regenerates over time; by default, new available cells replace expended cells. For example, the body regenerates a full bone within ten years, while non-injured skin tissue is regenerated within two weeks.<ref name=tedOrgans2009/> With injured tissue, the body usually has a different response. This emergency response usually involves building a degree of scar tissue over a time period longer than a regenerative response, as has been proven clinically<ref name=Cubison2006>{{cite journal |vauthors=Cubison TC, Pape SA, Parkhouse N |title=Evidence for the link between healing time and the development of hypertrophic scars (HTS) in paediatric burns due to scald injury |journal=Burns |volume=32 |issue=8 |pages=992–9 |date=December 2006 |pmid=16901651 |doi=10.1016/j.burns.2006.02.007}}</ref> and via observation.
Whereas 3rd degree burns heal slowly by scarring, in 2016 it was known that full thickness fractional [[photothermolysis]] holes heal without scarring.<ref name=regenByInstru2016/> Up to 40% of full thickness skin can be removed without scarring in an area, in a fractional pattern via coring of tissue.<ref name=regenByInstru2016/>
Some human organs and tissues regenerate rather than simply scar, as a result of injury. These include the liver, fingertips, and endometrium. More information is now known regarding the passive replacement of tissues in the human body, as well as the mechanics of [[stem cell]]s. Advances in research have enabled the induced regeneration of many more tissues and organs than previously thought possible. The aim for these techniques is to use these techniques in the near future for the purpose of regenerating any tissue type in the human body.{{cn|date=November 2024}}
==Regeneration techniques==
Line 37:
Various tissues that have been regenerated by in vitro 3D printing include:
* The first organ ever induced and made in the lab was the bladder, which was created in 1999.<ref name=regen2014104/>
* By 2014, there had been various tissues regenerated by the 3D printer and these tissues included: muscle, vagina, penis and the thymus.
* In 2014, a conceptual human lung was first bioengineered in the lab.<ref name=lung2014>{{cite web | url = https://www.wired.com/story/four-successful-bel-transplants/ | title = Bioengineers Are Closer Than Ever To Lab-Grown Lungs
| last =Gonzalez | first =Robbie | date =8 January 2018 | website = wired.com| access-date =27 May 2020 }}</ref><ref name=lung2018>{{cite journal |last1=Uriarte |first1=Juan J. |last2=Uhl |first2=Franziska E. |last3=Rolandsson Enes |first3=Sara E. |last4=Pouliot |first4=Robert A. |last5=Weiss |first5=Daniel J. |title=Lung bioengineering: advances and challenges in lung decellularization and recellularization |journal=Current Opinion in Organ Transplantation |date=December 2018 |volume=23 |issue=6 |pages=673–678 |doi=10.1097/MOT.0000000000000584 |pmid=30300330 |pmc=8669574 |s2cid=52946782 }}</ref> In 2015, the lab robustly tested its technique and regenerated a pig lung.<ref name=lung2014/><ref name=lung2018/> The pig lung was then successfully transplanted into a pig without the use of immunosuppressive drugs.<ref name=lung2014/><ref name=lung2018/>
* In 2015, researchers developed a proof of principle biolimb inside a laboratory; they also estimated that it would be at least a decade for any testing of limbs in humans. The limb demonstrated fully functioning skin, muscles, blood vessels and bones.<ref name=limb2015>{{cite web | last = Plaugic | first = Lizzie | title = Researchers have grown a partially functioning rat limb in a lab | website = theverge.com | publisher = washingtonpost.com | date = 4 June 2015 | url = https://www.theverge.com/2015/6/4/8730453/rat-limb-biolimb-regeneration-decellularization | access-date = 8 June 2015 }}</ref>
* In April 2019, researchers 3D printed a human heart.<ref name=regen3dHeart2019>{{cite web | url = https://edition.cnn.com/2019/04/15/health/3d-printed-heart-study/index.html
Line 52 ⟶ 50:
|-
! Level 1 !! Level 2!! Level 3!! Level 4
|-
| Skin || Blood vessel || Bladder || Heart
|-
| Muscle || Trachea|| ||Liver
|-
| Nails || Urethra|| ||Pancreas
|-
| Corneal Endothelium|| || ||Penis
|}
With printing tissues, by 2012, there were four accepted standard levels of regenerative complexity that were acknowledged in various academic institutions:
* Level one, ''flat tissue'' like skin was the simplest to recreate;<ref name=organRegen2012/>
* Level two was ''tubular structures'' such as blood vessels;<ref name=organRegen2012/>
* Level three was ''hollow non-tubular structures'';<ref name=organRegen2012/>
* Level four was ''solid organs'', which were by far the most complex to recreate due to the vascularity.<ref name=organRegen2012/>
Line 92 ⟶ 90:
===Endometrium===
The [[endometrium]] after the process of breakdown via the [[menstruation cycle]], re-epithelializes swiftly and regenerates.<ref name=CompleteRegen2>{{cite web | last1 = Min | first1 = Su | last2 = Wang | first2 = Song W. | last3 = Orr | first3 = William | title = Graphic general pathology: 2.2 complete regeneration | work = Pathology | publisher = pathol.med.stu.edu.cn | year = 2006 | quote = 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. | url = https://pathol.med.stu.edu.cn/pathol/listEngContent2.aspx?ContentID=492 | access-date = 2013-11-10 | url-status = dead | archive-url = https://web.archive.org/web/20121207231322/https://pathol.med.stu.edu.cn/pathol/listEngContent2.aspx?ContentID=492 | archive-date = 2012-12-07 }}</ref> Though tissues with a non-interrupted morphology, like non-injured soft tissue, completely regenerate consistently; the endometrium is the only human tissue that completely regenerates consistently after a disruption and interruption of the morphology.<ref name=CompleteRegen2/> The inner lining of the uterus is the only adult tissue to undergo rapid cyclic shedding and regeneration without scarring, shedding and restoring roughly inside a 7-day window on a monthly basis.<ref name=Scrrpr2012918>{{cite web| title = Endometrial repair| quote = Importantly, the endometrium is the only adult tissue to undergo rapid cyclic repair without scarring.| publisher = princehenrys.org| date = 18 September 2012 | url = https://www.princehenrys.org/endometrial-repair-menstruation| access-date = 30 June 2013| archive-url =https://web.archive.org/web/20090914010721/https://www.princehenrys.org/endometrial-repair-menstruation| url-status = dead| archive-date =2009-09-14}}</ref> All other adult tissues, upon rapid shedding or injury, can scar.{{cn|date=November 2024}}
===Fingers===
In May 1932, L. H. McKim published a report describing the regeneration of an adult digit-tip following amputation. A house surgeon in the [[Montreal General Hospital]] underwent amputation of the [[Phalanx bones|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.<ref>{{cite journal|last=McKim |first=L.H.|title=Regeneration Of The Distal Phalanx |journal=The Canadian Medical Association Journal|date=May 1932|pages=549–550 |pmid=20318716|pmc=402335|volume=26|issue=5}}</ref> This is one of the earliest recorded examples of adult human digit-tip regeneration.<ref>{{cite journal|last=Wicker |first=Jordan |author2=Kenneth Kamler |title=Current concepts in limb regeneration: A hand surgeon's perspective |journal=Annals of the New York Academy of Sciences |date=August 2009|volume=1172|issue=1 |pages=95–109 |pmid=19735243 |doi=10.1111/j.1749-6632.2009.04413.x |bibcode=2009NYASA1172...95W|s2cid=22948936 }}</ref>
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
In August 2005, Lee Spievack, then in his early sixties, accidentally sliced off the tip of his right middle finger just above the [[Phalanx bones|first phalanx]]. His brother, Dr. Alan Spievack, was researching regeneration and provided him with powdered [[extracellular matrix]], developed by Dr. Stephen Badylak of the [https://www.mirm.pitt.edu/ McGowan Institute] of [[Regenerative medicine|Regenerative Medicine]]. Mr. Spievack covered the wound with the powder, and the tip of his finger re-grew in four weeks.<ref name=MSNBC_20070219>{{cite news |access-date=October 24, 2008 |url=https://www.nbcnews.com/id/17171083 |archive-url=https://web.archive.org/web/20130302231241/https://www.nbcnews.com/id/17171083 |url-status=dead |archive-date=March 2, 2013 |title=Regeneration recipe: Pinch of pig, cell of lizard |agency=Associated Press |publisher=NBC News |date=February 19, 2007}}</ref> The news was released in 2007. [[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"<ref>{{cite news |url=https://www.theguardian.com/science/2008/may/03/medicalresearch.health |date=May 3, 2008 |work=The Guardian |title=The missing finger that never was |author=Goldacre, Ben}}</ref>
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.<ref>[https://www.cnn.com/2010/HEALTH/09/09/pinky.regeneration.surgery/index.html 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.</ref>
Line 106 ⟶ 104:
Regenerative capacity of the [[kidney]] has been recently explored.<ref>{{cite journal | doi = 10.1038/nm.3154 | volume=19 | title=Regeneration and experimental orthotopic transplantation of a bioengineered kidney | year=2013 | journal=Nature Medicine | pages=646–651 | author=Song Jeremy J | issue=5 | pmid=23584091 | pmc=3650107}}</ref>
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.{{cn|date=November 2024}}
In the mammalian kidney, the regeneration of the tubular component following an acute injury is well known. Recently regeneration of the [[Glomerulus (kidney)|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. Studies examining the capacity of bone marrow stem cells to differentiate into renal cells are emerging.<ref>{{cite journal | author = Kurinji | year = 2009 | title = In Vitro Differentiation of MSC into Cells with a Renal Tubular Epithelial-Like Phenotype | journal = Renal Failure | volume = 31 | issue = 6| pages = 492–502 |display-authors=etal | doi=10.1080/08860220902928981| pmid = 19839827 | doi-access = free }}</ref>
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, [[Skate (fish)|skates]], rays, and sharks. In these fish, the entire nephron regenerates following injury or partial removal of the kidney.{{cn|date=November 2024}}
===Liver===
Line 119 ⟶ 117:
===Vas deferens===
The [[vas deferens]] can grow back together after a [[vasectomy]]
==Induced regeneration==
There are several human tissues that have been successfully or partially induced to regenerate. Many fall under the topic of [[regenerative medicine]], which includes the methods and research conducted with the aim of regenerating the organs and tissues of humans as a result of injury. The major strategies of regenerative medicine include dedifferentiating injury site cells, transplanting stem cells, implanting lab-grown tissues and organs, and implanting bioartificial tissues.{{cn|date=November 2024}}
===Bladder===
In 1999, the bladder was the first regenerated organ to be given to seven patients; as of 2014, these regenerated bladders are still functioning inside the beneficiaries.<ref name=regen2014104>{{cite web | last =Mohammadi | first = Dara| title = Bioengineered organs: The story so
===Fat===
Line 133 ⟶ 131:
===Heart===
[[Cardiovascular disease]]s are the leading cause of death worldwide, and have increased proportionally from 25.8% of global deaths in 1990, to 31.5% of deaths in 2013.<ref name=WHO2011/> This is true in all areas of the world except [[Africa]].<ref name=WHO2011>{{cite book|last1=Mendis|first1=Shanthi|last2=Puska|first2=Pekka|last3=Norrving|first3=Bo|title=Global atlas on cardiovascular disease prevention and control|date=2011|publisher=World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization|location=Geneva|isbn=9789241564373|pages=3–18|edition=1st|url=https://whqlibdoc.who.int/publications/2011/9789241564373_eng.pdf?ua=1}}</ref><ref name=GDB2013>{{cite journal|author=((GBD 2013 Mortality and Causes of Death Collaborators)) |title=Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.|journal=Lancet|date=17 December 2014|pmid=25530442|doi=10.1016/S0140-6736(14)61682-2|volume=385|issue=9963|pages=117–71|pmc=4340604}}</ref>
In addition, during a typical [[myocardial infarction]] or heart attack, an estimated one billion cardiac cells are lost.<ref>{{Cite journal|last1=Laflamme|first1=MA|last2=Murry|first2=CE|title=Regenerating the heart|journal=Nature Biotechnology|volume=23|issue=7|pages=845–56|date=July 2005|pmid=16003373|doi=10.1038/nbt1117|s2cid=8265954}}</ref>
The scarring that results is then responsible for greatly increasing the risk of life-threatening abnormal heart rhythms or [[cardiac arrhythmia|arrhythmias]]. Therefore, the ability to naturally regenerate the heart would have an enormous impact on modern healthcare. However, while several animals can regenerate heart damage (e.g. the [[axolotl]]), mammalian [[cardiac muscle cell|cardiomyocytes]] (heart muscle cells) cannot proliferate (multiply) and heart damage causes scarring and [[fibrosis]].{{cn|date=November 2024}}
Despite the earlier belief that human cardiomyocytes are not generated later in life, a recent study has found that this is not the case. This study took advantage of the [[nuclear weapon|nuclear bomb]] testing and other [[radioactive]] sources during the [[Atomic Age]] which introduced [[carbon-14]] into the [[atmosphere]] (essentially all of which had [[Radioactive decay|decayed]] up to that point in [[History of Earth|Earth's history]]) and therefore into the cells of biologically active inhabitants.<ref name="Bergmann2009">
Line 143 ⟶ 141:
</ref>
Further research has been conducted that supports the potential for human cardiac regeneration. Inhibition of [[p38 mitogen-activated protein kinases
One of the most promising sources of heart regeneration is the use of stem cells. It was demonstrated in mice that there is a resident population of stem cells or cardiac progenitors in the adult heart – this population of stem cells was shown to be reprogrammed to differentiate into cardiomyocytes that replaced those lost during a heart tissue death.<ref name="Smart2011">
Line 149 ⟶ 147:
</ref> In humans specifically, a "cardiac mesenchymal feeder layer" was found in the myocardium that renewed the cells with progenitors that differentiated into mature cardiac cells.<ref name="Laugwitz2005">
{{Cite journal |vauthors=Laugwitz KL, etal | title=Postnatal isl1+carioblasts enter fully differentiated cardiomyocyte lineages | journal=[[Nature (journal)|Nature]] | volume=433 | issue=7026 | year=2005 | pages=647–653| doi=10.1038/nature03215 | pmid=15703750| pmc=5578466 | bibcode=2005Natur.433..647L }}
</ref> What these studies show is that the human heart contains stem cells that could potentially be induced into regenerating the heart when needed, rather than just being used to replace expended cells.{{cn|date=November 2024}}
Loss of the myocardium due to disease often leads to heart failure; therefore, it would be useful to be able to take cells from elsewhere in the heart to replenish those lost. This was achieved in 2010 when mature cardiac [[fibroblasts]] were reprogrammed directly into cardiomyocyte-like cells. This was done using three [[transcription factors]]: [[GATA4]], [[Mef2c]], and [[TBX5 (gene)|Tbx5]].<ref name="Ieda2010">
{{Cite journal |vauthors=Ieda M, etal | title=Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors | journal=[[Cell (journal)|Cell]] | volume=142 | issue=3 | year=2010 | pages=375–386| doi=10.1016/j.cell.2010.07.002 | pmid=20691899 | pmc=2919844}}
</ref>
Cardiac fibroblasts make up more than half of all heart cells and are usually not able to conduct contractions (are not cardiogenic), but those reprogrammed were able to contract spontaneously.<ref name="Ieda2010" /> The significance is that fibroblasts from the damaged heart or from elsewhere, may be a source of functional cardiomyocytes for regeneration.{{cn|date=November 2024}}
Simply injecting functioning cardiac cells into a damaged heart is only partially effective. In order to achieve more reliable results, structures composed of the cells need to be produced and then transplanted. Masumoto and his team designed a method of producing sheets of cardiomyocytes and vascular cells from human [[induced pluripotent stem cell|iPSCs]]. These sheets were then transplanted onto infarcted hearts of rats, leading to significantly improved cardiac function.<ref name="Masumoto2014">
Line 167 ⟶ 165:
It has been shown that bone marrow-derived cells could be the source of progenitor cells of multiple cell lineages, and a 2004 study suggested that one of these cell types was involved in lung regeneration.<ref name="Ishizawa2004">
{{Cite journal |vauthors=Ishizawa K, etal | title=Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysemal | journal=[[FEBS]] | volume=556 | issue=1–3 | year=2004 | pages=249–252 | doi=10.1016/s0014-5793(03)01399-1| pmid=14706858 | s2cid=1334711 | doi-access=free | bibcode=2004FEBSL.556..249I }}
</ref> Therefore, a potential source of cells for lung regeneration has been found; however, due to advances in inducing stem cells and directing their differentiation, major progress in lung regeneration has consistently featured the use of patient-derived iPSCs and bioscaffolds.
The [[extracellular matrix]] is the key to generating entire organs in vitro. It was found that by carefully removing the cells of an entire lung, a "footprint" is left behind that can guide cellular adhesion and differentiation if a population of lung epithelial cells and [[chondrocytes]] are added.<ref name="Balestrini2015">
Line 175 ⟶ 173:
</ref>
A 2010 investigation
▲A 2010 investigation took this one step further by using the ECM scaffold to produce entire lungs in vitro to be transplanted into living rats.<ref name="Petersen2010">
{{Cite journal |vauthors=Petersen TH, etal | title=Tissue-Engineered Lungs for in Vivo Implantation |journal=[[Science (journal)|Science]] | volume=329 | issue=5991 | year=2010 | pages=538–541 |doi= 10.1126/science.1189345| pmid=20576850 |pmc=3640463 | bibcode=2010Sci...329..538P }}
</ref> These successfully enabled [[gas exchange]] but for short time intervals only.<ref name="Petersen2010" /> Nevertheless, this was a huge leap towards whole lung regeneration and transplants for humans, which has already taken another step forward with the lung regeneration of a non-human primate.<ref name="Bonvillain2012">
Line 187 ⟶ 181:
[[Cystic fibrosis]] is another disease of the lungs, which is highly fatal and genetically linked to a mutation in the [[Cystic fibrosis transmembrane conductance regulator|CFTR gene]]. Through growing patient-specific lung epithelium in vitro, lung tissue expressing the cystic fibrosis phenotype has been achieved.<ref name="Wong2012">
{{Cite journal |vauthors=Wong AP, etal | title=Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein| journal=[[Nature Biotechnology]] | volume=30 | issue=9| year=2012 | pages=876–882 | doi=10.1038/nbt.2328| pmid=22922672| pmc=3994104}}
</ref> This is so that modelling and drug testing of the disease pathology can be carried out with the hope of regenerative medical applications.{{cn|date=November 2024}}
===Penis===
Line 202 ⟶ 196:
==See also==
* [[Cloning]]
* [[Decellularization]]
* [[Induced pluripotent stem cell]]
* [[Life extension]]
* [[Rejuvenation (aging)]]
* [[Stem cell treatments]]
* [[Tissue engineering]]
==References==
| |||