Department of Pathology, Immunology and Laboratory Medicine, College
of Medicine, and Stem Cell Program, University of Florida, Gainesville,
Florida.
Correspondence to Dr. Bryon E. Petersen, P.O. Box 100275, Department of
Pathology, University of Florida, Gainesville, FL 32610. Phone: 352-392-6261;
Fax: 352-392-6249; E-mail:
petersen{at}pathology.ufl.edu
Stem cells are cells that are capable of self-renewal and aremultipotent,
meaning that they can differentiate into many specificcell types. For a long
time, "stem cell" had been a conceptin mammalian biology but not
a reality that could be seen, touched,and expanded in vitro, until
murine embryonic stem cell culturewas established in 1981. Through recent
progress made in adultstem cell research, we now can isolate various
stem/progenitorcells derived from adult tissues, such as neural stem cells,
vascularendothelial progenitor cells, and hepatic oval cells. Of themany
adult stem cells described in the literature (hematopoietic,neural, hepatic,
dermal, pancreatic, and intestinal), it oncewas thought that these cells
could differentiate only into thecell type from which they originated. It now
seems that theadult stem cell is more plastic, versatile, and capable of
becomingmany different types of cells, e.g., blood to brain/liver,
brainto blood, liver to blood. These new findings give the once lonelyadult
stem cell a new lease on life and perhaps a better chancein enabling both
investigators and clinicians to fight life-threateninghuman diseases. Recent
stem cell—based cell therapieshave been shown to be successful in
animal models for variousdiseases, such as Parkinson's disease and
insulin-dependentdiabetes mellitus. In the coming decade, the focus of
researchwill be stem cell—based cell therapy (or a combinationof cell
and gene therapy techniques). In this article, we discussthe present status
and the future of stem cell research viatwo major categories: embryonic stem
(ES) cells and adult stemcells. Self-renewal is discussed, mostly from a
point of viewof gene regulation in the ES cell and from a point of view of
themicroenvironment in the adult stem cell. In addition, the pluripotencyof
stem cells is addressed. Finally, we refer to the controversiesarising in
stem cell research and the future applications ofstem cells in medicine.
Not many people would argue against the statement that establishmentof
pluripotent murine ES cell culture is one of the great achievementsin
mammalian cell and developmental biology. ES cells are continuouslygrowing
stem cell lines of embryonic origin first isolated fromthe inner cell mass of
developing mouse blastocysts
(1,
2).The distinguished features
of ES cells are their capacity tobe maintained in an undifferentiated state
indefinitely in cultureand their potential to develop into every cell type of
the body.Indeed, ES cells were the only nontransformed mammalian stemcells
that could be propagated continuously in vitro until recently,when
culture methods of various adult stem cells were established.
Self-renewing, totipotent ES cells may provide a virtually unlimiteddonor
source for transplantation and tissue generation in vitroin the
future. Mouse ES cell—derived hematopoietic precursors,cardiomyocytes,
neural precursors, or insulin-producing cells,have been transplanted
successfully into recipient animals.Because human ES cells (and embryonic
germ cells) were isolatedand shown recently to have a similar potential for
differentiationas the mouse ES cells
(3,
4), these techniques may be
appliedin the near future to patients with various diseases. Ultimately,
invitro—generated tissues from human ES cells may take the
placeat least in part of organ transplantation. ES-derived tissue-specific
cellsalso will be an ideal source for drug efficacy and toxicitytesting
(5).
Counterbalancing the promise of ES cells are serious ethicalconcerns for
the use of human ES cells because it requires fertilizedhuman eggs to
establish them. Because of recent advances inmethods that establish various
stem cells from adult tissues,enthusiasm for the direct application of human
ES cells clinically,once extremely high at the close of the 20th century,
seemsto be waning gradually. However, the significance of studiesin the ES
cell as a prototype of pluripotent stem cells willgo unchanged. The mechanism
underlying self-renewal activityof stem cells has been studied in depth using
ES cells as describedbelow. In terms of clinical application, the methods
developedfor generation of tissue-specific cells from ES cells wouldbe
applied easily to adult stem cells. Hence, ES cells willremain important as a
research tool in the study of mammaliandevelopment (see
Figure 1).
Figure 1. Promise of embryonic stem (ES) cells. Self-renewable ES cells (mouse or
human) can differentiate into multiple lineages in vitro. This in
vitro differentiation system has been used to study gene regulation in
mammal development and roles of genes in specific tissues. Furthermore, ES
cell—derived tissues are now expected for cell transplantation therapy,
tissue engineering, and drug efficacy/toxicity tests. Counterbalancing the
promise of ES cells are ethical concerns for the use of human ES cells because
it requires fertilized human eggs to establish them.
Self-renewal is one of the most important characteristics ofstem cells.
Its molecular mechanism has been studied intensivelyin ES cells but is
incompletely understood. Mouse ES cells canproliferate in vitro in
an undifferentiated, pluripotent stateon a feeder layer of mouse embryonic
fibroblast cells or ina medium containing leukemia inhibitory factor (LIF)
(6). LIFbelongs to the
interleukin-6 (IL-6) cytokine family, which includesIL-6, IL-11, oncostatin
M, ciliary neurotropic factor, and cardiotropin-1
(7).The effect of LIF is
mediated through a cell surface receptor(LIFRß) and gp130, a common
receptor subunit of theIL-6 cytokine family. LIF binds with LIFRß, which
thenforms a high-affinity heterodimer complex with gp130. Amongthe signals
transduced by the LIFR complex, activation of STAT3was determined to be
indispensable for the maintenance of undifferentiatedES cells
(8,9,10).
Expression of a dominant negative mutantof STAT3 abrogated self-renewal of ES
cells and induced differentiationin the presence of LIF
(8). Furthermore, activation of
STAT3by forced dimerization of the molecule was sufficient for the
self-renewalof ES cells in the absence of LIF
(9). Because STAT3 is a
transcriptionfactor, self-renewal of ES cells likely is maintained by the
molecule(s)of which expression is regulated directly or indirectly by STAT3.
Itshould be noted that primate ES cells, including human ES cells,
differentiateor die in the absence of fibroblast feeder layers, even in the
presenceof LIF (3,
11). The molecular basis of
undifferentiating factorsremains unknown in human ES cells. It also is
unclear whetherhuman ES cells require STAT3 activation for self-renewal.
Oct3/4 is a POU-domain transcription factor expressed exclusivelyin early
embryonic cells and germ cells
(12). Both mouse andhuman ES
cells highly express Oct3/4 when they are maintainedundifferentiated and lose
expression when differentiated. Itwas demonstrated that expression of the
appropriate amount ofOct3/4 was critical for maintenance of undifferentiated
murineES cells (13).
According to the study, increase and decreasein Oct3/4 resulted in
mesodermal- and trophectodermal-like differentiationof the cells,
respectively. Although Oct3/4-deficient mouseembryos develop to the
blastocyst stage, the inner cell masscells are not pluripotent but restricted
to differentiationalong the extraembryonic trophoblast lineage
(14). These studiesindicate
that Oct3/4 is an essential factor for maintenanceof undifferentiated ES
cells. Oct3/4 seems not to be a directtarget of STAT3
(9). The STAT3 pathway and the
Oct3/4 pathwayrather are considered to be two separate pathways, both of
whichare working coordinately for self-renewal of ES cells
(13).
Maintenance of telomere length is another feature observed andrequired in
self-renewal of stem cells. Both mouse and humanES cells have prolonged
telomeres and high telomerase activity.The molecular mechanism by which ES
cells maintain telomerelength, however, is unknown. It is interesting that
recent studieshave revealed that telomere shortening is not a major reason
forcell senescence in rodent cells, whereas it is the major limitingfactor
in survival of human cells
(15,
16). Oxidative stressor other
factors may play more critical roles in senescenceof primary rodent cells. In
this sense, mouse ES cells shouldhave a feature to escape from this
senescence mechanism as well.
The most rigorous test of the developmental potential of mouseES cells is
their ability to contribute to all cell lineages,including the germ line of
chimeric animals. This ability, inconjunction with effective homologous
recombination of DNA inES cells, enabled us to generate knockout mice. In
addition,when injected into immunocompromised animals, both murine andhuman
ES cells form teratomas composed of multiple differentiatedtissues in all
three germ layers: ectoderm, mesoderm, and endoderm.In addition to these
in vivo tests, ES cells are able to differentiateinto multiple cell
types in vitro.
The in vitro differentiation of ES cells is induced basicallyby
removing the ES cells from the feeder layer of mouse embryonicfibroblast
cells or by removing LIF from the culture medium.When differentiating ES
cells are cultured in suspension onpetri dishes, ES cells aggregate and form
structures, termedembryoid bodies, that spontaneously differentiate into
variouscell types, including cardiac myocytes, neuronal cells, erythrocytes,
melanocytes,and others
(17,18,19).
Numerous attempts have been made to enrichand isolate specific tissue
precursors from differentiatingES cells. Enrichment and/or isolation of
certain types of cellshas been achieved in some cases by addition of various
growth/differentiationfactors or chemicals. For example, pure populations of
mastcells precursors can be obtained easily from mouse ES cellsusing IL-3
and stem cell factor (c-kit ligand)
(20). A combinationof basic
fibroblast growth factor, platelet-derived growth factor,and epidermal growth
factor can enrich glial precursors in differentiatingmouse ES cells
(21). In other cases,
tissue-specific precursorscan be sorted using fluorescence-activated cell
sorter basedon expression of specific markers on the cell surface.
Flk1-positivecells from mouse ES cells were demonstrated to serve as vascular
progenitors(22).
Tissue-specific promoter-derived drug selection has beenused to purify other
cell types, including cardiac myocytesand insulin-secreting cells
(23,
24). ES cells also can be
differentiatedinto specific lineages by co-culture with other cells.
Differentiationinto hematopoietic cells and dopaminergic neurons, for
instance,was induced when mouse ES cells were replated on feeder layersof
OP9 and PA6 cells, respectively
(25,
26). In addition tothe cell
types described above, mouse ES cells have been demonstratedto have a
potential to differentiate into chondrocytes, dendriticcells, and hepatocytes
in vitro
(27,28,29).
The most obviousapplications of ES-derived tissue-specific precursors is in
cell-replacementtherapies (5).
To date, mouse ES cell—derived hematopoieticprecursors
(30), cardiomyocytes
(22), neural precursors
(20,
25,
31),insulin-producing cells
(23), and mast cells
(32) have beentransplanted
successfully into recipient animals. Human ES cellsalso demonstrated a
potential to differentiate into cell typesof all three germ layers
(33,
34). In contrast to previous
studiesusing mouse ES cells, which were performed mostly within small
laboratories,more systematic approaches now are being undertaken to generate
humanES cell—derived tissue-specific cells at the industriallevel or
as a larger collaborative research effort.
In addition to its clinical application, in vitro differentiation
ofES cells has been used in basic science to study gene expressionduring
development of specific cell types. Because gene modulationtechniques,
including gene targeting, are well established inES cells, it is relatively
easy to identify a role of a specificgene in the development of a certain
cell lineage (35).
Furthermore,in combination with the techniques to purify tissue-specific
cellsdescribed above, we can determine the function of genes in aspecific
tissue solely by in vitro assay
(19,
30,
36).
Of the many different types of adult stem cells, the most widelyknown and
best studied are the hematopoietic stem cells (HSC).HSC have been studied
since the early 1960s with the ground-breakingwork of several investigators,
which showed that a populationof bone marrow (BM) cells transplanted into
lethally irradiatedmice could colonize the spleen and rescue the mice from
death(37,
38). These studies then were
taken a step further by Siminovitchet al.
(39), who showed that these
clonogenic cells could betransplanted into another irradiated animal and
rescue thatanimal as well and reconstitute its entire BM system. Throughthe
years, it was found that these clonogenic cells could beenriched through
various techniques by either the physical orthe surface characteristics that
are present on these cells
(40,
41).With the development of
clonal-based assays for all hematopoieticcell lineages and
cell-sorter—based fluorescence-antibodystaining of certain cell
populations, specific populations ofBM cells could be isolated
(42,
43). The isolation of these
subsetsof BM cells led to possible candidates for stem cells in themurine
model
(44,45,46).
In terms of research and understanding the molecular pathwaysof stem
cells, the hematopoietic field is far ahead of the restof the stem cell
world. The cytokine requirements, cell to cellinteractions, integrin
expression patterns, and transcriptionregulatory factors all have been well
documented and definedfor the HSC
(47,
48). Current theory for stem
cell researchprofesses a linear model of hierarchy, whereby naive stem cells
exposedto certain growth factors and/or cytokines will progressivelyacquire
specific intrinsic factors and differentiate into ahierarchy of
progeny/progenitor cells. These progenitor cellsare thought to be stem-like
themselves but restricted to thenumber of options (pathways) available to
them for differentiation
(47.
Despite the attractiveness of this linear model for the hematopoietic
lineageselection, recent evidence has begun to expose weaknesses insuch a
tight and neatly packaged theory. The emergence of bothtransgenic and
knockout mouse models in conjunction with a betterunderstanding of molecular
analysis of HSC and their progenyhas led to the realization that these stem
cells are very dynamic.The expression of certain key transcription factors
does notnecessarily mean commitment to one lineage versus another
lineage(49,
50), making lineage selection
considerably more difficultto understand than once thought. The complexity
grows even largerwhen one takes into account other factors, such as the
microenvironment(cell to cell contact and surrounding matrix), the positive
andnegative regulators of motility versus division, and factorsthat
control differentiation (growth factors and chemokines).When one looks at
stem cell biology, it is important to encompassa view that is flexible and
takes into account that nature hasprovided back-ups to back-ups and that
lineage commitment canhappen in a variety of ways.
Overall, with the number of recent studies demonstrating bloodto brain
(51), to muscle
(52), to liver
(53), and perhaps evento
kidney, the HSC may be more plastic than once thought, becausethey can give
rise to a number of different cell types
(Figure 2).If these HSC
possess the entire genome, then they shouldbe capable of becoming any cell
type if given the right setof signals. Even though the HSC seem to be very
different fromother cell types at first glance, they rely on the interactions
withtheir niches and regularly use similar mechanisms in doing so.HSC rely
heavily on the use of integrins not only for migrationand mobility but also
for maintaining their residence withinthe BM
(54). As seen in other adult
stem-cell systems, the interactionof extracellular matrix (ECM) and integrins
is used not onlyfor adhesiveness but also for both survival and proliferation
ofstem cells within the BM
(47). Thus, integrins may act
as acommon link to keep stem cells in place while maintaining their
proliferativepotential. In performing these chores, integrins carry a certain
versatilitythat makes them essential in stem cell physiology. They canboth
respond to the ECM surrounding them and transmit internalsignals to activate
various signaling pathways as well as receiveinternal signals from activated
growth factor pathways and respondby rearranging the ECM on the surface of
the stem cell (47).
Figure 2.In vivo and in vitro adult stem cell plasticity. Bone
marrow (BM) stem cells (hematopoietic stem cell [HSC] or mesenchymal stem cell
[MSC]) have been shown to give rise to endothelial cells of the vascular
system (72) and muscle
(52) as well as hepatocytes
(53,
65,
66) in vivo. In
addition, BM stem cells have been shown to participate in neural development
and vice versa (51,
73). In vitro stem
cells have been shown to produce bone, connective tissue, and cartilage
(57). Last, neural stem cells
from the adult mouse brain can contribute to the formation of chimeric chick
and mouse embryos and give rise to cells of all germ layers
(64). All of this demonstrates
that adult stem cells have a very broad developmental capacity. Someday, these
stem cells may be used in a variety of ways in the treatment of different
human diseases.
A formidable task in stem cell biology will be defining whichkey
component(s) within the niche is important and transmitsto the stem cells the
many properties that they display whilein that particular environment. The BM
is a perfect exampleof the complexities found in one niche. Within the BM
existsa vast number of different cell types (stromal cells, macrophages,
adipocytes),all of which produce a variety of cytokines and growth factors
thatwill influence the HSC and its inevitable differentiation pathway
(55).Although great success
has been seen over the years in the cultureof HSC, it still remains to be
seen whether HSC can be culturedin vitro in such away that they
remain stem cells. Once HSCare removed from their niche and placed into
culture, they beginto differentiate into a variety of hematopoietic cell
types.HSC seem to be a very social cell, meaning that they survivebetter in
culture when placed in a co-culture system with BMstroma. The reasons for
this phenomenon are still unknown, butit seems that the intrinsic properties
of the niche are extremelyimportant in maintaining stem cell survival and
proliferation.HSC are not the only cell type that requires co-culturing;
epidermalkeratinocytes also require fibroblasts to maintain optimal growth
andsurvival (56).
To add more complexity to the picture of the microenvironment,the BM also
may contain more than one type of stem cell. Itseems that the mesenchymal
stem cells (MSC) reside in the BMas well. These MSC are responsible for
differentiating intoa variety of cell types, including bone, muscle,
cartilage,adipocytes, and marrow stroma
(57). The MSC also seem to be
differentfrom HSC because they can replicate as an undifferentiated cell.
Furthermore,it seems that these MSC also can differentiate into cells ofthe
epithelial lineages, such as hepatic and neural, but wereunable to
differentiate into cells of the hematopoietic lineage
(58).
Until recently, it was thought that tissue-specific stem cellscould
differentiate only into cells of the original source (e.g.,hepatic
oval cells into hepatocytes and bile ductular epithelium).However, a number
of recent studies suggest that adult organ-specificstem/progenitor cells may
be capable of differentiating intocells that are different from the original
cell type. Two groupsshowed that stem cells of ectodermal origin can
differentiateinto blood cells
(51,
59,
60), whereas others showed
that MSCtransplanted into mice can differentiate into astrocytes, neurons,
andoligodendrocytes (61,
62). A recent study by
Miyazaki et al.(63)
showed that BM-derived cells migrate to the kidney andmay play a role in the
progression of renal injury. Althoughunexpected, this can be considered
within the realm of possibility.The next step in renal research should be to
determine whetherHSC and/or MSC can participate in the repair of the kidney
afterinjury. Finally, Clarke et al.
(64) showed that neural stem
cellsinjected into mouse blastocysts can give rise to all tissuetypes in the
newborn mouse.
Theise et al. (65)
and Alison et al.
(66) both provided evidence
thatthis phenomenon is not isolated to the rodent model. They showedthat
this pathway of blood to liver exists in humans as well,thus providing
preliminary evidence that this pathway mightbe a highly conserved defense
mechanism within the evolutionof mammals as a whole. In addition, Zanjani
et al. (67) showed
thathuman stem cells transplanted into the preimmune fetus of sheepcan
contribute to the architecture of the developing liver andother organs as
well. This suggests that stem cells may actuallybe recruited to sites of
injury where they receive key signalsfrom the microenvironment, which allows
them to differentiateinto the desired cell type. The reports by Theise et
al. andAlison et al. seem to demonstrate this theory in which
hostcells were able to repopulate partially an orthoptically transplanted
liverwhere liver damage had occurred
(59,
65,
66).
BM is a very complex tissue that performs many different functionsin the
body and contains a variety of cell types. Both HSC andMSC are rare cells
found within the BM. It has been shown thatthe cells move out of the yolk sac
to the aortagonad-mesonephrosregion of the fetus and from there move into the
embryonic liver.Around the time of birth, the cells migrate out of the liver
tothe BM environment; this movement is controlled through theSDF-1/CXCR4
homing interaction of the hematopoietic and stromalcells
(68). Data presented by
Petersen et al. (69)
showed thatSDF-1 and CXCR4 could be a plausible mechanism by which BM-derived
cellsare recruited to the injured liver. This raises some interesting
questionsregrading the prospects that different stem cells can residein the
same place and respond to different stimuli and perchanceeven have influence
over one another. Altogether, these findingsadd additional hurdles in
defining the molecular characteristicsof the stem cell and its niche. Time
and further experimentsin the phenotypic characterization of these
stem/progenitorcells eventually will lead to exciting and novel therapeutic
approachesfor a number of life-threatening diseases.
The battle lines have been drawn over the use of stem cellsin research,
particularly over the use of human ES and humanfetal stem cells. The issue at
the center of this controversyis the use of federal dollars to be spent on
cell/tissue derivedfrom the destruction of human life and the ethical
concernsof what these cells are going to be used for. Seventy membersof
Congress signed a letter of objection to the use of humanembryonic stem cells
in research and published it in the journalScience
(70), whereas more than 70
scientists, 67 of them Nobellaureates, voiced their strong support for the
stance takenby the National Institutes of Health in support of funding for
humanES cell research (71).
In August 2000, the National Institutesof Health released guidelines for the
use of federal money tosupport human stem cell research much to the dismay of
the conservativeright.
A recent article by Charles Karuthammer printed in the February12, 2001,
issue of TIME magazine (71)
warns of the impendingmonsters that we will be capable of creating if allowed
to continuethis line of investigation. Many people express these concernsand
believe that stem cell research is immoral, illegal, andunnecessary. Stem
cell scientists do not know where the majorbreakthroughs will come because
embryonic, fetal, and adultstem cells all hold scientific potential.
Application of findingsobtained from nonhuman research must await subsequent
adjudication,and until the story is complete, it is highly appropriate that
researchbe allowed to move forward. Understandably, rigorous guidelinesmust
be followed just as they are for organ donation.
Lessons learned from the recombinant DNA debate were usefulin considering
policies for the use of human ES and fetal stemcells. The process of policy
development was public, and committeesconsisted of individuals with very
diverse backgrounds of expertiseand opinions. Although public debate was and
still is contentious,a careful and well-thought-out analysis of the issues
prevailed,which allows researchers to be supported by federal dollars.The
results illustrate that government officials, scientists,and the public can
work together and draft guidelines that allcan abide by in this sensitive and
controversial area of investigation.
The plasticity of adult stem cells seems to be bright and possiblya better
choice over ES or fetal stem cells for the treatmentof patients based on
immune response mechanisms. The use ofone's own stem cells for treatment
would reduce the need forimmunosuppressive drugs (self to
self-transplantation) and wouldend the ethical issues surrounding the use of
ES and fetal stemcells. Nonetheless, ES and fetal stem cell research should
continuebecause the invaluable information gained from these cell systems
willprovide a better understanding on the manner in which to manipulateand
manage adult stem cells in a more proficient manner.
Future of Stem Cells and the New Field of Regenerative Medicine
Stem cell biologists will have to overcome two very differentobstacles to
succeed in making stem cells a viable tool in thetreatment of humans. The
first hurdle will be to maintain stemcells as undifferentiated cells in
culture. The second hurdlewill be to differentiate cells, such as ES cells,
down lineagecommitment pathways. It may be unrealistic to think that thecell
biologist will be able to reproduce the precise set ofsignals that a cell
receives in vivo that permits a cell toachieve full commitment. What
comes first? Is it the cell-to-cellcontact, the ECM, or perhaps the
cytokine/growth factor signaling?So far, the first switch that sends the cell
down the path ofcommitment has been elusive. There are far too many signals
beingsent to the cell for us to decipher. It makes sense to try todevelop
culture systems that allow stem cells to proliferateand survive as stem cells
and use these cells as a source forgene/cell therapy techniques.
Transplanting these stem-likecells into the site of preference and allowing
the microenvironmentof the body to set into motion the proper signals seems
to bea logical approach to developing the desired cell type. However,in the
case of ES cells, it will be essential to initiate thepathway of commitment
before transplanting them into humans.When ES cells are transplanted into
mice, the cells developinto teratoma. Thus, the problem will not be to grow
them ina stem-like state but to direct them down various lineage pathways
withouttaking them so far that they become useless for transplantation.
If this occurs in the next few years—and by all indications,it seems
that it is likely to succeed—a great deal ofnew therapeutic uses can be
foreseen. Among these new therapieswill be the generation of different types
of neural cells forthe treatment of degenerative diseases such as Alzheimer's
andParkinson's. It would be within the realm of possibility thatspinal cord
injury patients may regain full function of theirbody. Even some genetic
disorders could be cured, not just treated.For example, stem cells from a
patient with hemophilia couldbe isolated and grown in culture, then
transfected with theclotting factor(s) gene(s) and transplanted back into the
patient'sliver.
These stem cells also could be used as building blocks in themaking of
artificial organs, such as the liver or kidney orperhaps even heart muscle.
Clearly, there are major hurdlesto overcome, including the problem of
differentiation discussedpreviously and the ability to devise
three-dimensional structuresin which the matrix will disintegrate while the
cells buildthere own matrix. Bioengineers and material scientists are already
addressingthese matrix problems. Medical centers all over the world havebeen
using artificial skin (dermal cells grown in culture) formore than two
decades and with great success in helping severelyburned patients recover
from their injuries. Clearly, more workneeds to be accomplished to overcome
the complexities of organdevelopment, but being able to grow somatic cells in
cultureover a long period of time (hepatocyte long-term cultures) andto take
some stem cell types (e.g., MSC) and begin their differentiationdown
distinct lineages are critical first steps for making theonce seemingly
unrealistic into reality.
In conclusion, the possibilities for stem cell—based therapiesseem
limitless. The German philosopher Nietzsche once said,"Many a man fails
as an original thinker simply because hismemory is too good." It is
this type of mentality that has keptthe blinders on many very prominent
scientists, which may haveslowed the pace of stem cell research. This may or
may not havebeen a bad thing. Fortunately, it now seems that the blinders
havebeen taken off and stem cell research is now proceeding at avery rapid
pace; through the use of stem cells, a host of humanailments possibly may be
eliminated in the not-too-distant future.It took billions of years of
evolution to produce cells thatcarry the awesome power to develop
independently through a veryprecise set of instructions enabling them to
differentiate intoanything from a liver cell to a kidney cell to a fully
grownorganism. The stem cell dogmas of yesterday are not withstandingthe
research findings of today, and many investigators are discoveringthat what
once was, is no longer. Now that we stand at the crossroads,do we try to
harness this power for the good of humankind despitea plethora of potential
problems, or do we turn our back onthe potential opportunity to cure a vast
number of sick peoplethroughout the world who require organ replacement? It
is imperativethat we, the stem cell scientists, work with the public
officialsto address the difficult questions that lies ahead. We havealready
begun the process with the new National Institutes ofHealth guidelines, but
the process must continue. To gain thesupport of the public, we must keep
them informed and includethem in the decision- making process as well. As
scientists,we cannot and must not forge recklessly ahead without gaining
publicsupport. What should give all of us reason to stop and contemplateis
not from where the cells originated but the sheer power thatthese cells
possess, which is the essence of life itself.
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Received for publication April 16, 2001.
Accepted for publication May 4, 2001.
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Introduction
ES Cells
