You are on page 1of 26

Shed in Regenerative Dentistry

Growing research works are necessary to adopt new techniques, for advancements and for better
treatment modalities in clinical field of dentistry. SHED is nothing but Stem cells from Human
Exfoliated Deciduous teeth. Stem cell research is one of the most popular of all the ongoing research
works which can be applied to regenerative procedures in clinical dentistry. From the information
obtained from many research works the exfoliated human deciduous tooth contains multipotent
stem cells which are identified to be a population of highly proliferative, clonogenic cells capable of
differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. In vivo
transplantation of these cells were found to be able to induce bone formation, generate dentin.
Ongoing research suggests that these stem cells will soon be used for dental purposes such as to
replace lost bone around teeth, periodontal ligament or dental pulp; treat periodontal disease; and
someday even produce new teeth, as well as for medical applications. In order for dentists to fully
participate in this new role, they should become aware of the applications, clinical use, and banking
of dental stem cells. Dentists can be involved in the extraction, collection, and storage of the stem
cells from their patients' teeth.


NCBI
S
kip to main content
S
kip to navigation
Resources
How To
A
bout NCBI Accesskeys
Sign in to NCBI
PMC
US National Library of Medicine
National Institutes of Health
Search termSearch database



PMC



Search
Limits
Advanced
Journal list
Help
Journal List
Indian J Med Res
v.135(6); Jun 2012
PMC3410208

Indian J Med Res. 2012 June; 135(6): 813819.
PMCID: PMC3410208
Chiranjib Chakraborty and Govindasamy Agoramoorthy
*

Author information Article notes Copyright and License information
Abstract
Go to:
Introduction
Evolutionary biologist Theodosius Dobzhansky once wrote Nothing in
biology makes sense except in the light of evolution
1
. The term light of
evolution was used earlier by biologist and statesman of science, Julian
Huxley. In fact, the notion light of evolution originally came from Pierre
Teilhard de Chardin, who was admired by Dobzhansky. The latter then
went on to say that species diversity in planet Earth cannot be explained
by the creation fairy tale because of the ecological complexity
1
. The
question however is, whether or not the evolution of stem cell started
with unicellular organism with its evolutionary linkage? The answer may
be hidden behind the properties of the stem cell of self-renewal and
differentiation. For example, single cell organisms have unique
capabilities not only to renew by self but also perform differentiated role.
On the contrary, stem cells in higher organisms have the ability to both
self-renew through mitotic cell division and differentiate into a diverse
range of specialized cell types.
Fossil evidence indicates the existence of uni-cellular prokaryotes on
Earth over 3.5 billion years ago
2
. One of the foremost muticellular
organisms was seaweed that came into existence about 1,300 million
years ago
3
. So the existence of stem cells could be traced back to millions
of years and these were developed through the process of natural
selection. Accordingly, the appearance of stem cells could be viewed as
fundamental in the lengthy evolutionary saga. In this review we have
highlighted stem cells in the light of evolution. We have outlined details
on stem cell multicellularity, regeneration and coloniality potential in the
organismic and evolutionary perspectives.
Go to:
Stem cells and multicellularity
The distribution of stem cells has been recorded throughout the animal
and plant kingdoms, and all these organisms are known to be
multicellular. However, during the development of multicellular
organisms through natural selection, stem cells accompanied the
evolutionary process, either in the mode of asexual or sexual
reproduction
4
. In general, stem cells can be separated by two basic
strategies
2,47
. One is asymmetric cell division and the other is stochastic
differentiation. In the asymmetric cell division, there are mechanisms
that might be described as invariant in which a stem cell gives rise
through asymmetric cell division
8
splitting into a stem daughter while
the other undergoes differentiation. In the case of stem cell, due to
asymmetric cell division, the cells first undergo a divide and produce one
daughter like itself that maintains stem cell characteristics while the
other programmed to differentiate into a non-stem cell fate leading to
the path of differentiation. Such a division can be seen in single cell
organisms and invertebrates. Asymmetric cell divisions occur during the
develop-ment of Drosophila and Caenorhabditis elegans
9
. Similarly,
multicellular organisms with a relatively few cell types can go though
such splitting. In the multicellular hydra, head and foot can be
regenerated in adult from a tiny piece of tissue mass from the body
column
10
.
Stem cell follows another route of cell division which is stochastic
differentiation. Here the stem cells make a combination of asymmetric
divisions and symmetric ones. Finally, they produce either two stem cells
(symmetric renewal), or two differentiated cells (symmetric
differentiation). Some reports show that in olfactory epithelium
11
and
muscle
12
stem cell follows the stochastic differentiation cell division.
Go to:
Stem cells and regeneration potential
Regeneration has received renewed research interest in recent years.
Stem cells have been extensively studied due to their regeneration
potential. First, this property was shown by histologists in the
19
th
century who introduced an abstract term for cells which can
specifically repair or regeneration potential. With the discovery of bone
marrow cells in the 1950s, the haematopoietic stem cell concepts started
to emerge
13
. Haematopoietic stem cells are accountable for the steady
renewal of the blood cells while mesenchymal stem cells, a group of
stromal cells show multilineage segregation ability. Mesenchymal stem
cells have been isolated from different multicellular organism like
human
4
. The process in which a stem cell gives rise to daughter cells with
definite probability of being either stem cells or committed progenitors is
evident in a vast majority of mammalian self-renewing tissues.
Generally, each stem cell division gives rise to a stem and a committed
daughter at stable state. However, unevenness can be achieved on a
population basis rather than individual cell division basis. Moreover, in
some tissues there may be a range of cell behaviour with stem and
progenitor cells at opposite ends of a spectrum instead of discrete stem
and progenitor populations
1417
. Nevertheless, great variability in the self-
renewal process by a stem cell does occur
18
. In simple single cell
organisms such as the amoeba for example, a simple cell division is
equivalent to reproduction by which a new organism is created more
frequently
19
. Stem cells of small rodents on the contrary are estimated to
replicate about once in four weeks- for cats, it is once in per ten weeks
and for higher primates once in 50 wk
20
. This is largely due to the
intricacy of self-renewal process enhanced by natural selection.
In early animals, single cell carry out several physiological functions
while serving as stem cell. A classical example is hydra where single
epithelial cells appear to carryout several steady-state physiological
functions while serving as stem cell
21
. These cells perform both the
process of self-renewal and differentiation. Hydra belongs to the
exclusively aquatic phylum of Cnidaria- these early branching-animals
have survived for millions of years; they do not undergo ageing
(senescence) hence biologically eternal. This natural everlasting
characteristic can be attributed by the asexual mode of reproduction via
budding- it simply requires a tiny tissue of stem cells with continuous
self-renewal capability. Stem cell differentiation in the hydra is governed
by co-ordinated actions of conserved signaling pathways. Hence, the
hydra's stem cell represents a critical insight of general significance of its
biology (i.e. cellular senescence, lineage programming and
reprogramming, extrinsic signals in fate determination, tissue
homeostasis) and the ultimate evolutionary origin
22
.
The role of genes in vertebrate regeneration has received great interest
among the scientific community and studies have been targeted to cross-
examine gene transcription and protein translation during different
steps regeneration
2326
. Maki et al
23
reported that the expression of some
genes namely Sox2, Klf4, and c-myc have been unregulated when it
comes to regenerating potential. These three genes are in fact the most
important induced pluripotent stem cell (iPSC) genes which can be
unregulated in regenerating new lens and limb.
The zebrafish fins and Xenopus limbs have also become important
models for the study of regeneration. In regenerating zebrafish fins,
homologues of genes are related with the pluripotency and expressed to
initiate the regeneration process
27
. Scientists have concluded that
blastema cells in zebrafish fins andXenopus limbs are not completely
analogous to induced pluripotent mammalian stem cells but these tend
to share some similarities in gene expression
26
. A study of zebrafish tail
fins by Stewart et al
28
has concluded that histone demethylase is
necessary for regeneration by identifying targets of histone methylases
and demonstrating histone modifications silence promoters of numerous
genes involved in regeneration. The regulatory genes contain bivalent
me(3)K4/me(3)K27 H3 histone modifications created by the concerted
action of Polycomb (PcG) and Trithorax histone methyltransferases.
During the evolutionary process, regeneration appears to be common
among the adults of many non-vertebrate organisms. However, among
the adult vertebrates, amphibians like the salamanders are unique in a
way that they could regenerate limbs
29,30
. During the larval stage, the
developing limb bud is poised of undifferentiated cells while the adult
limb is composed of fully differentiated tissues. The limb stem cells
appear to help in the regeneration process
31
. On the other hand, it has
been reported that adult human has less potential of regeneration
compared to other group of organisms. Nonetheless, some parts such as
the skin fingertips, ribs, liver, kidney and heart have the capacity to
regenerate and repair themselves to some extent where adult stem cells
have been found in very low frequency
3234
. It appears that the
evolutionary process might have created the less occurrence of adult
stem cell in humans.
Go to:
Stem cells and coloniality
Coloniality comprises large congregation of individuals in a place that
includes the same species living together with a mutual advantage of
self-protection. It is an important question in evolution that how group-
living organisms assemble together and how the colonial origin came
into existence that harbours over a million individuals breeding and
living in proximity. Colonial behaviour itself is an evolutionary
ambiguity because individuals pay fitness costs to breed in high
densities
35
. However, the coloniality character has been recorded among
some phyla, specifically the tunicates, cnidarians, entoprocta, ectoprocta
and bryozoans
36
. Ascidians are one of the members of chordates that
belong to the Tunicata phyla and they offer unique opportunities to
investigate the biology of stem cells. At larval stage, the Ascidiains have a
typical chordate body plan including notochord, dorsal hollow nerve
tube and striated musculature. Subsequent to its swimming stage, the
larvae settle and undergo extensive metamorphosis
37
. At that stage
chordate characteristics are resorbed and ultimately end up as filter
feeding sessile invertebrate mature animal. Due to its small size and
rapid development, Ascidian larvae have been used widely as a model to
study specification and differentiation events of developmental biology
since they exhibit solitary and colonial forms. Solitary ones can reach up
to 10 cm while the colonial variety can spread up to several meters
2
. The
colonial ascidians have two developmental pathways to create an
identical adult thus unique among chordates with regenerative capability
and became an outstanding model for embryonic and stem cells
research
38
.
One peculiar taxon known as Botryllid ascidian has become a model for
allorecognition studies because of the allogeneic fusions revealing the
evolutionary links between allorecognition, stem cell biology and
ecology
39
. These colonial ascidians live in superficial sea water in all
temperate zones around the world
40
. After hatching from their
colony, Botryllus tadpoles larvae swim to surface where these attach and
undergo metamorphosis resulting in the loss of chordate characteristics
(tail, notochord, neural tube, and segmented musculature through the
apoptosis)
41
. At the beginning of bud formation, the vesicle cells are
morphologically undifferentiated; these stem cells can self-renew during
asexual reproduction. These take part in organogenesis and gonad
formation and these occur in clonemates in a vascular fused colony. So
the genomes of circulating germline stem cells and somatic stem cells are
the same and it is obvious that the individual tadpole is a target of
natural selection. Colony fusion offers the opportunity for germline stem
cells or somatic stem cells to move from one colony to a genetically
distinct colony
42
.
Another example of coloniality is the hydrozoan colonies. This fauna is a
member of the Cnidaria phyla. These colonies consist of multiple polyps
connected together by tube like structure and all colonial include some
polyps specialized for reproduction. The hydrozoan contains a
population of migratory stem cells and the epithelial cells of the colonies
serve as stem cell for some physiological process
20,43
. Presently, the
hydrozoan colonies are point of attraction to study evolution
44
. However,
the characteristic of coloniality in different organisms also proves the
characteristic of multicellularity.
Go to:
Stem cell evolution in branching vertebrates and mammals
In early branching vertebrates such as fish and amphibians, adult stem
cells are within the organ, for example, retinal stem cells are found in the
periphery of the retina while the ciliary marginal zone produces new
neurons in retina throughout life. In these species, retina grows to keep
pace with the enlargement of body. However, among higher vertebrates
such as birds and mammals, when they reach adulthood, the retina stops
growing so there appears to be no need for such a proliferative area with
stem cells. A study suggests that a region similar to the ciliary marginal
zone of fish and amphibians exists in the post-natal chick and adult
mouse
45
.
In mammals, some evidence supports the properties of stem cell
evolution. Due to larger size and longer life, larger mammals require
more blood cells. As a matter of fact, the total number of human
haematopoietic stem cells (HSCs) is equivalent to the total number of
HSCs in cat and mouse. This fact strongly supports that the number of
HSCs per animal is conserved in mammals
46
. After injury, active adult
stem cells help to renew and regenerate the tissue. It is an essential
physiological phenomenon in all mammals
47
. This example shows the
evidence of conservation of active adult stem cell in mammals.
Go to:
Stem cell and regulatory gene networks
How does the regulatory gene network perform behind the stem cell in
the light of evolution? Various factors such as the microenvironment,
signaling events and genetic characteristics are often associated with this
property of stem cell
48
. Models like Clytia hemisphaerica are available to
analyze how stem cell intrinsic factors are integrated with signaling
events, and how the microenvironment of stem cell niche maintains
tissue homeostasis
22
. In the early branching-animal of Clytia, for
example, nematoblasts occur between ectodermal epithelial cells within
the tentacle bulbs from where the tentacles grow. The tentacle bulbs are
spherical outgrowths of bell margin of medusa. Spatial progression of
nematoblast stages along the bulb axis is correlated with differential
stem cell marker gene expression. Most of the cells at the base of the
tentacle bulb express Clytia Piwi homologue gene but not a
differentiation marker
49
. In fact, the Piwi gene is a widely conserved
stem cell marker throughout multicellular eukaryotes, and these cells
might be considered as a population of stem cells
50,51
.
In several invertebrate groups, especially sponges and planarians, tissue
plasticity and regeneration capacity based on stem cells are the common
characteristics. These organisms harbour a Piwi gene, which is a
conserved gene for regeneration and plasticity. Piwi homologues have
been identified from freshwater sponge, Ephydatia fluviatilis, as
candidate stem cell (archeocyte) markers
52
. Planarian regeneration is
based upon totipotent stem cells, the neoblasts. Piwi, especially DjPiwi-
1, has been identified from planarian stem cells during the regeneration
process of the stem cell
53
. DjPiwi-1gene of planaria is a homologue
of Drosophila piwi. This gene is a member of the PAZ-Piwi gene family
and can be used as a marker for stem cell.
Would it be possible for a stem cell gene to change over evolutionary
time? Computational tools and development of genomic resources could
lend a hand to answer the ultimate evolutionary function of stem cells. In
organisms such as the cnidarians, bilaterians and metazoans, Sox2 is
known to date as one of the most conserved stem cell-specific genes
54
.
Cnidarians and bilaterians were known to have diverged over 560
million years ago and the discovery of Sox2 in early branching
metazoans suggests that there is a similarity of the regulator gene of
stem cell potency that might have present in both groups. The presence
of stem cell marker gene like Sox2 strongly supports the above evidence
that appears to be highly conserved. However, Nanog or Oct 3/4 is
present in metazoans
55
. On the other hand, there is another example of
preserved regulatory gene of a stem cell like wnt gene. The wntpathway
has been recorded in the preservation of D. melanogaster germ,
mammalian haematopoietic, gut, and hair follicle stem cells
5659
.
This wnt gene has been conserved in different stem cells during the
process of evolution through natural selection.
As a matter of fact, stem cells and their niches evolved in the
multicellular organisms and have many features that are conserved
between vertebrates and Drosophila. One of the well characterized stem
cell niches resides at the tip of the Drosophila ovary where it regulates
germline stem cells. Subsequent types of stem cell, escort stem cells, also
reside in this niche and interact closely with germline stem cells. These
escort stem cells division provides one or two squamous cells that wrap
each developing germ cell cyst and suggests how niche facilitates co-
ordinated activity of these two types of stem cells. Gut stem cells are
likely to be controlled by a niche that differs from the germline stem cells
or escort stem cells niche in two respects. A niche cell might act as an
anchor of the stem cell in position though it is not clear
60
. Further, the
niche appears to repress most gut stem cells in a temporally and spatially
regulated manner and most evidence suggests that multicellularism
evolved separately. Nonetheless the piwi gene in Drosophila is more
conserved
61
. It is evident that evolution enveloped systematic regulatory
gene network in stem cell for self-renewal process formed by Oct4, Sox2,
and Nanog, in particular, controlling embryonic stem (ES) cell
pluripotency in mammals
62
that are also more conserved.
Go to:
Conclusions
Evolutionary theories are based on single gene homologies or cross-
kingdom gene transfer assisting convergent evolution through
biochemical processess in plants and animals
63
. Plants have been ignored
focus as a resource for stem cell research because single cells from adult
plants have the ability to make complete new adult plants
6466
. Despite
this, plants and animals have some homology, both organisms evolved
separately influenced by natural selection. The homology between
the piwi gene in Drosophila, which controls germ line stem cells, and
the ZWILLE gene in Arabidopsis, which controls the stem cells of the
shoot meristem has led to the suggestion that stemness evolved in a
single-celled ancestor, or plants and animals might have shared a
multicellular ancestor
5
. In Metazoans, Drosophila, C. elegans, and all
vertebrates, studies suggest that natural selection otherwise adhering to
the principles of Mendel and Hardy-Weinberg and the mechanisms
might have been due to fitness selection
6770
. However, during the
evolutionary process, sequestration of cells in one conspecific animal
from another is not the rule; many species tend to exist wherein
genotypically distinct cells may intermix within a chimeric entity
71,72
. The
ideas of stem cell-based organogenesis and stem cell-based regeneration
are interrelated and developed through the evolutionarily selection
process
42
. Therefore, stem cells are not only the entity of biological
organization, accountable for the progress and the regeneration of tissue
and organ systems, but also are units in the complex evolutionary
process. However, more understanding between the relationships and
dynamics of molecular signatures and gene regulatory circuits behind
stem cell will lead us to know more about the stem cell in the light of
evolution.
Go to:
References
1. Dobzhansky T. Biology, molecular and organismic. Am
Zoo. 1964;4:44352. [PubMed]
2. Fenchel T. Origin and early evolution of life. Oxford, UK: Oxford
University Press; 2002.
3. Erwin DH, Valentine JW, Jablonski D. The origin of animal body
plans. Am Sci. 1997;85:12637.
4. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca
JD, et al. Multilineage potential of adult human mesenchymal stem
cells. Science. 1999;284:1437. [PubMed]
5. Loeffler M, Potten CS. Stem cells and cellular pedigrees - a conceptual
introduction. In: Potten CS, editor. Stem cells. London: Academic Press;
1997. pp. 127.
6. Hall PA, Watt FM. Stem cells: the generation and maintenance of
cellular diversity. Development.1989;106:61933. [PubMed]
7. Morrison SJ, Shah NM, Anderson DJ. Regulatory mechanisms in stem
cell biology. Cell.1997;88:28798. [PubMed]
8. Neumller RA, Knoblich JA. Dividing cellular asymmetry: asymmetric
cell division and its implications for stem cells and cancer. Genes
Dev. 2009;23:267599. [PMC free article] [PubMed]
9. Knoblich JA. Asymmetric cell division during animal
development. Nat Rev Mol Cell Biol. 2001;2:1120. [PubMed]
10. Jones PH, Harper S, Watt FM. Stem cell patterning and fate in
human epidermis. Cell. 1995;80:8393. [PubMed]
11. Lander AD, Gokoffski KK, Wan FY, Nie Q, Calof AL. Cell lineages and
the logic of proliferative control. PLoS Biol. 2009;7:e15. [PMC free
article] [PubMed]
12. Manceau M, Gros J, Savage K, Thome V, McPherron A, Paterson B, et
al. Myostatin promotes the terminal differentiation of embryonic muscle
progenitors. Genes Dev. 2008;22:66881.[PMC free article] [PubMed]
13. Whited JL, Tabin CJ. Regeneration review reprise. J
Biol. 2010;9:15. [PMC free article] [PubMed]
14. Jensen UB, Lowell S, Watt FM. The spatial relationship between stem
cells and their progeny in the basal layer of human epidermis: a new
view based on whole-mount labelling and lineage
analysis.Development. 1999;126:240918. [PubMed]
15. Zhu AJ, Haase I, Watt FM. Signaling via beta1 integrins and mitogen-
activated protein kinase determines human epidermal stem cell fate in
vitro. Proc Natl Acad Sci USA. 1999;96:6732838.[PMC free
article] [PubMed]
16. Jones PH, Watt FM. Separation of human epidermal stem cells from
transit amplifying cells on the basis of differences in integrin function
and expression. Cell. 1993;73:71324. [PubMed]
17. Jones PH, Harper S, Watt FM. Stem cell patterning and fate in
human epidermis. Cell. 1995;80:8393. [PubMed]
18. Till JE, McCulloch EA, Siminovitch L. A stochastic model of stem cell
proliferation based on the growth of spleen colony-forming cells. Proc
Natl Acad Sci USA. 1964;51:2936. [PMC free article][PubMed]
19. Morgan DO. The cell cycle: Principles of control. London: New
Science Press; 2007.
20. Lanza R, Gearhart J, Hogan B, Melton D, Pedersen R, Thomas ED, et
al., editors. Essentials of stem cell biology. USA: Academic Press; 2006.
p. 548.
21. Bode HR. The interstitial cell lineage of hydra: a stem cell system that
arose early in evolution. J Cell Sci. 1996;109:115564. [PubMed]
22. Bosch TCG. Hydra and the evolution of stem
cells. Bioessays. 2009;31:47886. [PubMed]
23. Maki N, Suetsugu-Maki R, Tarui H, Agata K, Del Rio-Tsonis K,
Tsonis PA. Expression of stem cell pluripotency factors during
regeneration in newts. Dev Dyn. 2009;238:16136. [PMC free
article][PubMed]
24. Christen B, Robles V, Raya M, Paramonov I, Izpisua Belmonte JC.
Regeneration and reprogramming compared. BMC Biol. 2010;8:5. [PMC
free article] [PubMed]
25. King MW, Neff AW, Mescher AL. Proteomics analysis of regenerating
amphibian limbs: changes during the onset of regeneration. Int J Dev
Biol. 2009;53:95569. [PubMed]
26. Rao N, Jhamb D, Milner DJ, Li B, Song F, Wang M, et al. Proteomic
analysis of blastema formation in regenerating axolotl limbs. BMC
Biol. 2009;7:83. [PMC free article] [PubMed]
27. Christen B, Robles V, Raya M, Paramonov I, Izpisa Belmonte JC.
Regeneration and reprogramming compared. BMC
Biol. 2010;20(8):5. [PMC free article] [PubMed]
28. Stewart S, Tsun ZY, Izpisua Belmonte JC. A histone demethylase is
necessary for regeneration in zebrafish. Proc Natl Acad Sci
USA. 2009;106:1988994. [PMC free article] [PubMed]
29. Wallace H. Vertebrate limb regeneration. Chichester: John Wiley and
Sons; 1981.
30. Mullen LM, Bryant SV, Torok MA, Blumberg B, Gardiner DM. Nerve
dependency of regeneration: the role of Distal-less and FGF signaling in
amphibian limb regeneration. Development. 1996;122:3487
97. [PubMed]
31. Bryant SV, Endo T, Gardiner DM. Vertebrate limb regeneration and
the origin of limb stem cells. Int J Dev Biol. 2002;46:88796. [PubMed]
32. Michalopoulos GK, DeFrances MC. Liver
regeneration. Science. 1997;276:606. [PubMed]
33. Michael SR. 15
th
Annual World Congress on Anti-Aging Medicine and
Regenerative Biomedical Technologies. Chicago, Illinois: American
Academy of Anti-Aging Medicine, Chicago; 2007. Aug 2-4, PCO40-Bio-
scalar technology: regeneration and optimization of the body-mind
homeostasis. 2007.
34. Hicok KC, Du Laney TV, Zhou YS, Halvorsen YD, Hitt DC, Cooper
LF, et al. Human adipose-derived adult stem cells produce osteoid in
vivo. Tissue Eng. 2004;10:37180. [PubMed]
35. Danchin E, Wagner RH. The evolution of coloniality: the emergence
of new perspectives. Trends Ecol Evol. 1997;12:3427. [PubMed]
36. Skld HN, Obst M, Skld M, kesson B. Stem cells in asexual
reproduction of marine invertebrates. In: Rinkevich B, Matranga V,
editors. Stem cells in marine organisms. New York: Springer-Verlag;
2009. pp. 10537.
37. Satoh N. An advanced filter-feeder hypothesis for urochordate
evolution. Zoolog Sci. 2009;26:97111. [PubMed]
38. Tiozzo S, Brown FD, De Tomaso AW. Regeneration and stem cells in
ascidians. In: Bosch TC, editor.Stem cells: From hydra to man. Berlin:
Springer; 2008. pp. 95112.
39. Rinkevich B. The colonial urochordate Botryllus schlosseri: from
stem cells and natural tissue transplantation to issues in evolutionary
ecology. Bioessays. 2002;24:7304. [PubMed]
40. Grosberg RK. Competitive ability influences habitat choice in marine
invertebrates. Nature.1981;290:7002.
41. Lauzon RJ, Patton CW, Weissman IL. A morphological and
immunohistochemical study of programmed cell death in Botryllus
schlosseri (Tunicata, Ascidiacea) Cell Tissue Res. 1993;272:115
27.[PubMed]
42. Weissman IL. Stem cells: units of development, units of
regeneration, and units in evolution. Cell.2000;100:15768. [PubMed]
43. Martin VJ. Differentiation of the interstitial cell line in hydrozoan
planulae. Hydrobiol. 1991;216-217:7582.
44. Cartwright P, Nawrocki AM. Character evolution in hydrozoa
(phylum Cnidaria) Int Comp Biol.2010;50:45672. [PubMed]
45. Perron M, Harris WA. Retinal stem cells in
vertebrates. Bioessays. 2000;22:6858. [PubMed]
46. Abkowitz JL, Catlin SN, McCallie MT, Guttorp P. Evidence that the
number of hematopoietic stem cells per animal is conserved in
mammals. Blood. 2002;100:26657. [PubMed]
47. Li L, Clevers H. Coexistence of quiescent and active adult stem cells
in mammals. Science.2010;327:5425. [PubMed]
48. Fernandez-Tresguerres B, Caon S, Rayon T, Pernaute B, Crespo M,
Torroja C, et al. Evolution of the mammalian embryonic pluripotency
gene regulatory network. Proc Natl Acad Sci USA.2010;107:19955
60. [PMC free article] [PubMed]
49. Denker E, Manuel M, Leclre L, Le Guyader H, Rabet N. Ordered
progression of nematogenesis from stem cells through differentiation
stages in the tentacle bulb of Clytia hemisphaerica (Hydrozoa,
Cnidaria) Dev Biol. 2008;315:99113. [PubMed]
50. Lin H, Spradling AC. A novel group of pumilio mutations affects the
asymmetric division of germline stem cells in the Drosophila
ovary. Devt. 1997;124:246376. [PubMed]
51. Rebscher N, Zelada-Gonzlez F, Banisch TU, Raible F, Arendt D.
Vasa unveils a common origin of germ cells and of somatic stem cells
from the posterior growth zone in the polychaete Platynereis
dumerilii. Dev Biol. 2007;306:599611. [PubMed]
52. Funayama N, Nakatsukasa M, Mohri K, Masuda Y, Agata
K. Piwi expression in archeocytes and choanocytes in demosponges:
insights into the stem cell system in demosponges. Evol
Devel.2010;12:27587. [PubMed]
53. Rossi L, Salvetti A, Lena A, Batistoni R, Deri P, Pugliesi C, et
al. DjPiwi-1, a member of the PAZ-Piwi gene family, defines a
subpopulation of planarian stem cells. Dev Genes Evol. 2006;216:335
46.[PubMed]
54. Jager M, Quinnec E, Le Guyader H, Manuel M. Multiple Sox genes
are expressed in stem cells or in differentiating neuro-sensory cells in the
hydrozoan Clytia hemisphaerica. Evodevo. 2011;2:12.[PMC free
article] [PubMed]
55. Hemmrich G, Bosch TC. Compagen, a comparative genomics
platform for early branching metazoan animals, reveals early origins of
genes regulating stem-cell differentiation. Bioessays.2008;30:1010
8. [PubMed]
56. Song X, Xie T. Wingless signaling regulates the maintenance of
ovarian somatic stem cells in Drosophila. Development. 2003;130:3259
68. [PubMed]
57. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, et al.
A role for Wnt signalling in self-renewal of haematopoietic stem
cells. Nature. 2003;423:40914. [PubMed]
58. Lickert H, Domon C, Huls G, Wehrle C, Duluc I, Clevers H, et al.
Wnt/(beta)-catenin signaling regulates the expression of the homeobox
gene Cdx1 in embryonic intestine. Development.2000;127:3805
13. [PubMed]
59. Merrill BJ, Gat U, DasGupta R, Fuchs E. Tcf3 and Lef1 regulate
lineage differentiation of multipotent stem cells in skin. Genes
Dev. 2001;15:1688705. [PMC free article] [PubMed]
60. Ohlstein B, Kai T, deCotto E, Spradling AC. The stem cell niche:
theme and variation. Curr Opin Cell Biol. 2004;16:6939. [PubMed]
61. Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H. A novel class of
evolutionarily conserved genes defined by piwi are essential for stem cell
self-renewal. Genes Dev. 1998;12:371527. [PMC free article][PubMed]
62. Sun Y, Li H, Yang H, Rao MS, Zhan M. Mechanisms controlling
embryonic stem cell self-renewal and differentiation. Crit Rev Eukaryot
Gene Expr. 2006;16:21131. [PubMed]
63. Benfey PN. Stem cells: A tale of two kingdoms. Curr
Biol. 1999;9:R171. [PubMed]
64. Steward FC, Mapes MO, Mears K. Growth and organized
development of cultured cells. II. Organization in cultures grown from
freely suspended cells. Am J Bot. 1958;45:7058.
65. Vasil V, Hildebrande AC. Differentiation of tobacco plants from
single, isolated cells in microcultures.Science. 1965;150:889
92. [PubMed]
66. Dodeman VL, Ducreux G, Kreis M. Zygotic embryogenesis versus
somatic embryo-genesis. J Exp Bot. 1997;48:1493509.
67. Edwards AW, Hardy GH. (1908) and Hardy-Weinberg
equilibrium. Genetics. 2008;179:114350.[PMC free article] [PubMed]
68. Mendel G. Experiments in plant hybridization (1865). Read at the
February 8
th
and March 8
th
, 1865, meetings of the Brnn Natural History
Society. 1866:347.
69. Buss LW. The evolution of individuality. Princeton, NJ: Princeton
Univ. Press; 1987.
70. Blackstone NW, Jasker BD. Phylogenetic considerations of clonality,
coloniality, and mode of germline development in animals. J Exp Zool B
Mol Dev Evol. 2003;297:3547. [PubMed]
71. Buss LW. Slime molds, ascidians, and the utility of evolutionary
theory. Proc Natl Acad Sci USA.1999;96:88013. [PMC free
article] [PubMed]
72. Magor BG, De Tomaso A, Rinkevich B, Weissman IL. Allorecognition
in colonial tunicates: protection against predatory cell
lineages? Immunol Rev. 1999;167:6979. [PubMed]

Articles from The Indian Journal of Medical Research are provided here courtesy
of Medknow Publications

Formats:
Article
|
PubReader
|
ePub (beta)
|
Printer Friendly
Related citations in PubMed
Epigenetic regulation of stem cell fate.[Hum Mol Genet. 2008]
The potential use of myogenic stem cells in regenerative medicine.[Handb Exp Pharmacol. 2006]
Skeletal muscle stem cells in developmental versus regenerative myogenesis.[J Intern Med. 2009]
Regeneration next: toward heart stem cell therapeutics.[Cell Stem Cell. 2009]
Commitment of stem cells into functional hepatocytes.[Differentiation. 2010]
See reviews...See all...
Links
PubMed
Taxonomy
Taxonomy Tree
Recent Activity
ClearTurn Off
Stem cells in the light of evolution
PMC
See more...
Multilineage potential of adult human mesenchymal stem cells.[Science. 1999]
Review Regulatory mechanisms in stem cell biology.[Cell. 1997]
Review Dividing cellular asymmetry: asymmetric cell division and its implications for
stem cells and cancer.[Genes Dev. 2009]
Review Asymmetric cell division during animal development.[Nat Rev Mol Cell Biol.
2001]
Stem cell patterning and fate in human epidermis.[Cell. 1995]
Cell lineages and the logic of proliferative control.[PLoS Biol. 2009]
Myostatin promotes the terminal differentiation of embryonic muscle progenitors.[Genes
Dev. 2008]
Review Regeneration review reprise.[J Biol. 2010]
Multilineage potential of adult human mesenchymal stem cells.[Science. 1999]
The spatial relationship between stem cells and their progeny in the basal layer of human
epidermis: a new view based on whole-mount labelling and lineage
analysis.[Development. 1999]
Stem cell patterning and fate in human epidermis.[Cell. 1995]
A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE
GROWTH OF SPLEEN COLONY-FORMING CELLS.[Proc Natl Acad Sci U S A.
1964]
Review The interstitial cell lineage of hydra: a stem cell system that arose early in
evolution.[J Cell Sci. 1996]
Hydra and the evolution of stem cells.[Bioessays. 2009]
Expression of stem cell pluripotency factors during regeneration in newts.[Dev Dyn.
2009]
Proteomic analysis of blastema formation in regenerating axolotl limbs.[BMC Biol.
2009]
Regeneration and reprogramming compared.[BMC Biol. 2010]
Proteomic analysis of blastema formation in regenerating axolotl limbs.[BMC Biol.
2009]
A histone demethylase is necessary for regeneration in zebrafish.[Proc Natl Acad Sci U S
A. 2009]
Nerve dependency of regeneration: the role of Distal-less and FGF signaling in
amphibian limb regeneration.[Development. 1996]
Review Vertebrate limb regeneration and the origin of limb stem cells.[Int J Dev Biol.
2002]
Review Liver regeneration.[Science. 1997]
Human adipose-derived adult stem cells produce osteoid in vivo.[Tissue Eng. 2004]
The evolution of coloniality: the emergence of new perspectives.[Trends Ecol Evol.
1997]
Review An advanced filter-feeder hypothesis for urochordate evolution.[Zoolog Sci.
2009]
Review The colonial urochordate Botryllus schlosseri: from stem cells and natural tissue
transplantation to issues in evolutionary ecology.[Bioessays. 2002]
A morphological and immunohistochemical study of programmed cell death in Botryllus
schlosseri (Tunicata, Ascidiacea).[Cell Tissue Res. 1993]
Review Stem cells: units of development, units of regeneration, and units in
evolution.[Cell. 2000]
Character evolution in Hydrozoa (phylum Cnidaria).[Integr Comp Biol. 2010]
Review Retinal stem cells in vertebrates.[Bioessays. 2000]
Evidence that the number of hematopoietic stem cells per animal is conserved in
mammals.[Blood. 2002]
Review Coexistence of quiescent and active adult stem cells in mammals.[Science. 2010]
Evolution of the mammalian embryonic pluripotency gene regulatory network.[Proc Natl
Acad Sci U S A. 2010]
Hydra and the evolution of stem cells.[Bioessays. 2009]
Ordered progression of nematogenesis from stem cells through differentiation stages in
the tentacle bulb of Clytia hemisphaerica (Hydrozoa, Cnidaria).[Dev Biol. 2008]
A novel group of pumilio mutations affects the asymmetric division of germline stem
cells in the Drosophila ovary.[Development. 1997]
Vasa unveils a common origin of germ cells and of somatic stem cells from the posterior
growth zone in the polychaete Platynereis dumerilii.[Dev Biol. 2007]
Piwi expression in archeocytes and choanocytes in demosponges: insights into the stem
cell system in demosponges.[Evol Dev. 2010]
DjPiwi-1, a member of the PAZ-Piwi gene family, defines a subpopulation of planarian
stem cells.[Dev Genes Evol. 2006]
Multiple Sox genes are expressed in stem cells or in differentiating neuro-sensory cells in
the hydrozoan Clytia hemisphaerica.[Evodevo. 2011]
Compagen, a comparative genomics platform for early branching metazoan animals,
reveals early origins of genes regulating stem-cell differentiation.[Bioessays. 2008]
Wingless signaling regulates the maintenance of ovarian somatic stem cells in
Drosophila.[Development. 2003]
Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin.[Genes
Dev. 2001]
Review The stem cell niche: theme and variations.[Curr Opin Cell Biol. 2004]
A novel class of evolutionarily conserved genes defined by piwi are essential for stem
cell self-renewal.[Genes Dev. 1998]
Review Mechanisms controlling embryonic stem cell self-renewal and
differentiation.[Crit Rev Eukaryot Gene Expr. 2006]
Review Stem cells: A tale of two kingdoms.[Curr Biol. 1999]
G. H. Hardy (1908) and Hardy-Weinberg equilibrium.[Genetics. 2008]
Phylogenetic considerations of clonality, coloniality, and mode of germline development
in animals.[J Exp Zool B Mol Dev Evol. 2003]
Review Slime molds, ascidians, and the utility of evolutionary theory.[Proc Natl Acad
Sci U S A. 1999]
Allorecognition in colonial tunicates: protection against predatory cell
lineages?[Immunol Rev. 1999]
Review Stem cells: units of development, units of regeneration, and units in
evolution.[Cell. 2000]
You are here: NCBI > Literature > PubMed Central (PMC)
Write to the Help Desk


Development Genes and Evolution
Springer-Verlag Berlin Heidelberg 2012
10.1007/s00427-012-0430-8
Editorial
Stem cells in the context of evolution and
development
Volker Hartenstein
1

(1)
Department of Biology, University of California Los Angeles, 621 Charles E. Young Dr, Los Angeles,
CA 90095-1606, USA


Volker Hartenstein
Email: volkerh@mcdb.ucla.edu
Received: 2 November 2012Accepted: 12 November 2012Published online: 6 December 2012
Without Abstract
The field of stem cell biology originated and grew around the discovery that it was possible
to isolate undifferentiated cells (stem cells) from various adult organs, as well as from early
mammalian embryos. These could then be grown in culture, made to differentiate into
various cell types, and put back into host organisms. It gradually became clear that most, if
not all, adult tissues possess stem cells, and that neoplastic growth typically takes off from
stem cells. Since the implications for the cure of cancer and degenerative diseases are great,
research on the biology of stem cells has expanded rapidly over the past two decades. In
particular, stem cell research has moved into using genetic model systems, including the
invertebrates Drosophila and Caenorhabditis elegans, and into investigations of stem cell
development (in vertebrates and Drosophila alike). Both approaches have delivered
significant new insights. In small organisms such as Drosophila, stem cell pools and their
niche environment often consist of only a few cells, and questions concerning the pattern of
cell division, niche-stem cell contacts, or differentiation can be addressed at the single cell
level (as for example, in the gonadal stem cells and the intestine; Spradling et al.2011; Eliazer
and Buszczak 2011; Papagiannouli and Lohmann 2012; Jiang and Edgar 2012; Takashima
and Hartenstein 2012). Studying the development of stem cells offers the opportunity to
follow step by step where in the embryo these cells come from, what structures in their
environment they interact with, and what signaling pathways are active sequentially as a
result of these interactions.
Stem cells of the adult organism are typically slowly cycling, undifferentiated, and often
multipotent cells located in special microenvironments, called niches (Martinez-Agosto et
al. 2007; Haegebarth and Clevers2009; Boral and Nie 2012). Embryonic stem cells can be
molecularly defined by a small number of transcription factors and signaling pathways
(Boyer et al. 2006; Loh et al. 2008; Chambers and Tomlinson2009) which are crucial for self
renewal, and which are even able to induce embryonic stem (ES) cell characteristics when
expressed in mature cells. The combination of ES stemness factors found in ES cells is not
typically expressed in adult stem cells of vertebrates, or other model organisms; instead, adult
somatic stem cells typically express markers specific for an individual organ or tissue (e.g.,
membrane glycoprotein CD34 in hematopoietic stem cells; Lgr5 in intestinal stem cells;
Leushacke and Barker 2012). Through their mitotic activity, stem cells generate two types of
offspring. First, they renew themselves and thereby maintain a pool of proliferating stem
cells. Secondly, they produce offspring that then become postmitotic and differentiate or
(more typically) that first undergo a phase of rapid cell division before differentiating. Since
these cells have a limited proliferative potential and eventually turn into differentiated
progeny, they are referred to as transient amplifying cells.
The great interest in stem cells, whether analyzed in a culture system or in model organisms,
has also spawned lines of research that aim at the evolutionary origin and subsequent
modifications of this fundamental cell type. Many areas of early research received an infusion
of new concepts and new technologies. Hydrozoa and Planaria, to name but two examples,
have long been known for their amazing capacity of regeneration, and the existence of
multipotent stem cells (i.e., interstitial cells and neoblasts, respectively) play an important
role in regeneration and normal development (Gierer 1977; Chandebois 1976). More
recently, new technologies have permitted the investigation of refined questions about these
stem cells, including questions concerning the signaling pathways controlling their behavior
and the batteries of genes that are turned on or off depending on the developmental state
(Bosch et al. 2010; Tanaka and Reddien 2011; Bagu 2012). The quickly expanding field of
comparative stem cell biology notably also includes flowering plants, organisms that clearly
outdo animals when it comes to vegetative growth (Aichinger et al. 2012). Throughout the
ensuing studies, a question that naturally looms in the background is how related, in terms of
genetic constitution and developmental potential, are these primordial stem cell systems to
the stem cells that we observe in highly derived bilaterians? Can one consider multipotent
stem cells as fundamentally homologous? Or did they evolve separately from a primitive
state that lacked professional stem cells, where cell renewal occurred by division of
differentiated cells, or by dedifferentiation (followed by division) of these cells?
A satisfactory answer to these and many other questions cannot yet be provided, because our
knowledge of stem cells outside the few model organisms is far too sketchy. In an effort to
bring together information on stem cells by studying multiple different taxa, we collected a
set of review articles in this special issue of DGE. In these articles, attention is paid to the
questions of developmental origin, lineage potential, and possible homologies of stem cells.
The first two articles (Ereskovsky et al. 2013; Funayama 2013) address these issues in
sponges. They emphasize the overall conservation in terms of cell movements and
morphogenesis that exists between sponges and higher animals and summarize the growing
body of evidence for a dual system of stem cells, choanocytes, and archaeocytes as the
mechanism underlying growth and regeneration in this animal taxon. The next pair of papers
(Galliot 2013; Gold and Jacobs 2013) surveys stem cells of Cnidaria. Hydra, as one member
of this taxon, has yielded important insights in the developmental questions of regeneration,
organizers, morphogen gradients, and, more recently, specific signaling pathways underlying
these phenomena. The article by Galliot summarizes recent research on the interplay between
apoptosis, interstitial stem cells, and epithelial stem cells that takes place during injury-
induced head regeneration. Gold and Jacobs take a comparative look into the different types
of stem cells that have been identified (or affirmed to exist) in Cnidaria outside the
hydrozoans. With the paper by Rink (2013) we move into the bilaterian animals, more
specifically, the planarians, members of the diverse phylum Platyhelminthes; the review
provides an overview of stem cell characteristics that gradually become established for the
neoblasts. The last four articles focus on different classes of somatic stem cells, including
those of the intestine, blood, heart, and nervous system. Takashima et al. (2013) survey in a
comparative manner the developmental mechanisms of producing and maintaining the cell
types found in animal guts. Grigorian and Hartenstein (2013) take a look at the process of
hematopoiesis in a more restricted set of taxa, the arthropods. The contribution by Pandur et
al. (2013) reviews recent data pertaining to the embryonic fields that give rise to tissues,
including stem cells, of the vertebrate heart. Finally, Grandel and Brand (2013) focus on the
central nervous system of vertebrates, where the fairly restricted distribution and function of
neural stem cells found in mammals contrast with the widespread occurrence of these cells in
anamniotes; despite this discrepancy, detailed comparisons looking at stem cell development
and proliferative mechanisms reveal a number of common themes throughout vertebrates.
We hope the articles of this special issue will be of help as a source of information for
researchers in stem cell biology, as well as interested readers who will try to draw together
concepts and ideas that are spawned by discoveries in the fields of evolution, development,
and stem cells.
References
Aichinger E, Kornet N, Friedrich T, Laux T (2012) Plant stem cell niches. Annu Rev Plant Biol 63:615
636PubMedCrossRef
Bagu J (2012) The planarian neoblast: the rambling history of its origin and some current black boxes. Int J Dev Biol
56(13):1937PubMedCrossRef
Boral D, Nie D (2012) Cancer stem cells and niche microenvironments. Front Biosci (Elite Ed) 4:25022514CrossRef
Bosch TC, Anton-Erxleben F, Hemmrich G, Khalturin K (2010) The Hydra polyp: nothing but an active stem cell
community. Dev Growth Differ 52(1):1525PubMedCrossRef
Boyer LA, Mathur D, Jaenisch R (2006) Molecular control of pluripotency. Curr Opin Gen Dev 16(5):455462
Chambers I, Tomlinson SR (2009) The transcriptional foundation of pluripotency. Development 136(14):23112322
Chandebois R (1976) Histogenesis and morphogenesis in planarian regeneration. Monogr Dev Biol 11:1182PubMed
Eliazer S, Buszczak M (2011) Finding a niche: studies from the Drosophila ovary. Stem Cell Res Ther 2(6):45. doi:10.1186/
scrt86PubMedCrossRef
Ereskovsky AV, Renard E, Borchiellini C (2013) Cellular and molecular processes leading to embryo formation in sponges:
evidences for high conservation of processes throughout animal evolution. Dev Genes Evol. doi:10.007/s00427-012-0399-3
Funayama N (2013) The stem cell system in demosponges: suggested involvement of two types of cells: archeocytes (active
stem cells) and choanocytes (food-entrapping flagellated cells). Dev Genes Evol. doi:10.007/s00427-012-0417-5
Galliot B (2013) Injury-induced asymmetric cell death as a driving force for head regeneration in Hydra. Dev Genes Evol.
doi:10.007/s00427-012-0411-y
Gierer A (1977) Biological features and physical concepts of pattern formation exemplified by hydra. Curr Top Dev Biol
11:1759PubMedCrossRef
Gold D, Jacobs D (2013) Stem cell dynamics in Cnidaria: are there unifying principles? Dev Genes Evol. doi:10.1007/
s00427-012-0429-1
Grandel H, Brand M (2013) Comparative aspects of adult neural stem cell activity in vertebrates. Dev Genes Evol. doi:10.
007/s00427-012-0425-5
Grigorian M, Hartenstein V (2013) Hematopoiesis and hematopoietic organs in arthropods. Dev Genes Evol. doi:10.007/
s00427-012-0428-2
Haegebarth A, Clevers H (2009) Wnt signaling, lgr5, and stem cells in the intestine and skin. Am J Pathol 174(3):715
721PubMedCrossRef
Jiang H, Edgar BA (2012) Intestinal stem cell function in Drosophila and mice. Curr Opin Genet Dev 22(4):354
360PubMedCrossRef
Leushacke M, Barker N (2012) Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer.
Oncogene 31(25):30093022. doi:10.1038/onc.2011.479PubMedCrossRef
Loh YH, Ng JH, Ng HH (2008) Molecular framework underlying pluripotency. Cell Cycle 7(7):885891PubMedCrossRef
Martinez-Agosto JA, Mikkola HK, Hartenstein V, Banerjee U (2007) The hematopoietic stem cell and its niche: a
comparative view. Genes Dev 21(23):30443060PubMedCrossRef
Pandur P, Sirbu IO, Khl SJ, Philipp M, Khl M (2013) Islet1-expressing cardiac progenitor cells: a comparison across
species. Dev Genes Evol. doi:10.007/s00427-012-0400-1
Papagiannouli F, Lohmann I (2012) Shaping the niche: lessons from the Drosophila testis and other model systems.
Biotechnol J 7(6):723736. doi:10.1002/biot.201100352PubMedCrossRef
Rink J (2013) Stem cell systems and regeneration in Planaria. Dev Genes Evol. doi:10.007/s00427-012-0426-4
Spradling A, Fuller MT, Braun RE, Yoshida S (2011) Germline stem cells. Cold Spring Harb Perspect Biol 3(11):a002642.
doi:10.1101/cshperspect.a002642PubMedCrossRef
Takashima S, Hartenstein V (2012) Genetic control of intestinal stem cell specification and development: a comparative
view. Stem Cell Rev 8(2):597608PubMedCrossRef
Takashima S, Gold D, Hartenstein V (2013) Stem cells and lineages of the intestine: a developmental and evolutionary
perspective. Dev Genes Evol. doi:10.007/s00427-012-0422-8
Tanaka EM, Reddien PW (2011) The cellular basis for animal regeneration. Dev Cell 21(1):172185PubMedCrossRef


INTRODUCTION:
Stem cells hold particular promise for unlocking
life-saving secrets of the cell. Stem cells show potential for
many different areas of health and medical research, and
studying them can help us understand how they transform
into the dazzling array of specialized cells that make us what
we are. This promising area of science is also leading
scientists to investigate the possibility of cell-based
therapies to treat disease, which is often referred to as
regenerative or reparative medicine. The dual capacity of
stem cells for self-renewal and for differentiation into
particular types of cells and tissues offers great potential for
1
regenerative medicine .
ROLE OF STEM CELLS IN DENTISTRY:
Stem cells have the potential to repair and regenerate dental
tissues like dentin, tooth, bone, cartilages, skin, adipose
tissues, and glands. The research of stem cells in scientific
and therapeutic potential in oro-facial diseases is yet not
reached its pinnacle but future is flamboyant in regenerative
2 dentistry .
Scientists report for the first time that baby teeth, the
temporary teeth that children begin losing around their sixth
birthday, contain a rich supply of stem cells in their dental
pulp. The researchers say this unexpected discovery could
have important implications because the stem cells remain
alive inside the tooth for a short time after it falls out of a
childs mouth, suggesting the cells could be readily
3,4 harvested for research .
SHED (Stem Cells from Human Exfoliated Deciduous teeth) - A new source
of stem cells in dentistry
1 2 3 4 5 Raghavendra M. Shetty , Pooja Prasad , Sunaina Shetty , Vishal patil , Ramprasad V Anushka
6 Deoghare
1. Professor, Department of Pediatric Dentistry, Chhattisgarh Dental College and Research Institute,
Rajnandgaon, 491 441, Chhattisgarh, India
2. Senior Lecturer, Department of Oral and Maxillofacial Pathology, Chhattisgarh Dental College and
Research Institute, Rajnandgaon, 491 441, Chhattisgarh, India.
3. Senior Lecturer, Department of Periodontics, Chhattisgarh Dental College and Research Institute,
Rajnandgaon, 491 441, Chhattisgarh, India.
4. Professor, Department of Prosthodontics , Vasanthdada Patil Dental College, Sangli
5. Professor, Department of Oral and Maxillofacial Surgery, Maitri Dental College Anjora,
Chhattisgarh, India
6. Post graduate student, department of pedodontia, CDCRI, Rajnandgaon, CG
Correspondence Address :
Raghavendra M. Shetty, Professor, Department of Pediatric Dentistry, Chhattisgarh Dental College
and
Research Institute, Rajnandgaon, 491 441, Chhattisgarh (India). E-Mail:raghavendra77@yahoo.com
Abstract:
Tooth development results from sequential and reciprocal interactions between the oral epithelium
and the underlying neural crest-derived
mesenchyme. The generation of dental structures and/or entire teeth in the laboratory depends
upon the manipulation of stem cells and requires a
synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard
tissues, dentin and enamel. Although mesenchymal
stem cells from different origins have been extensively studied in their capacity to form dentin in
vitro, information is not yet available concerning the
use of epithelial stem cells. The odontogenic potential resides in the oral epithelium and thus
epithelial stem cells are necessary for both the initiation of
tooth formation and enamel matrix production. This article gives the insight to the regeneration of
dental tissues by Stem Cells from Human Exfoliated
Deciduous teeth (SHED).
Key Words: Enamel; Cyst; Dentin; Pulpal Tissue; Tumor: SHED
INTRODUCTION:
Stem cells hold particular promise for unlocking
life-saving secrets of the cell. Stem cells show potential for
many different areas of health and medical research, and
studying them can help us understand how they transform
into the dazzling array of specialized cells that make us what
we are. This promising area of science is also leading
scientists to investigate the possibility of cell-based
therapies to treat disease, which is often referred to as
regenerative or reparative medicine. The dual capacity of
stem cells for self-renewal and for differentiation into
particular types of cells and tissues offers great potential for
1
regenerative medicine .
ROLE OF STEM CELLS IN DENTISTRY:
Stem cells have the potential to repair and regenerate dental
tissues like dentin, tooth, bone, cartilages, skin, adipose
tissues, and glands. The research of stem cells in scientific
and therapeutic potential in oro-facial diseases is yet not
reached its pinnacle but future is flamboyant in regenerative
2 dentistry .
Scientists report for the first time that baby teeth, the
temporary teeth that children begin losing around their sixth
birthday, contain a rich supply of stem cells in their dental
pulp. The researchers say this unexpected discovery could
have important implications because the stem cells remain
alive inside the tooth for a short time after it falls out of a
childs mouth, suggesting the cells could be readily
3,4 harvested for researc