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One of the greatest challenges in t
One of the greatest challenges in the treatment of
inner-ear disorders is to find a cure for the hearing loss
that is caused by the loss of cochlear hair cells or spiral
ganglion neurons. The recent discovery of stem cells in
the adult inner ear that are capable of differentiating
into hair cells, as well as the finding that embryonic
stem cells can be converted into hair cells, raise hope
for the future development of stem-cell-based treatment
regimens. Here, we propose different approaches
for using stem cells to regenerate the damaged inner
ear and we describe the potential obstacles that translational
approaches must overcome for the development
of stem-cell-based cell-replacement therapies for
the damaged inner ear.
The sense of hearing is integral to our interaction with our
environment, yet the cellular components of the inner ear
are vulnerable to a variety of damaging agents. All hearing
sensation is derived from the output of a remarkably small
number of sensory cells: fewer than 15 000 per inner ear.
These hair cells are the mechanoelectrical transducers of
the ear; deflections of the stereociliary bundles (the hairlike
structures that give hair cells their name) on their
apical surfaces lead to transmitter release from their
basolateral poles, leading, in turn, to action potentials in
the auditory nerve fibers.
Most types of congenital and acquired hearing loss arise
from damage to, or loss of, cochlear hair cells or their
associated neurons. The incidence of heritable deafness is
high: one child in a thousand is born deaf; another one in a
thousand becomes deaf before adulthood [1,2]. Depending
on the age of onset, hearing impairment can affect oral
language acquisition, cognitive development and psychosocial
development. The prevalence of acquired hearing
loss is rising, as the population of the world increases
and ages and as noise pollution steadily increases. It is
estimated that one in three adults over the age of 65
has a handicapping hearing loss, making this condition
one of the most common chronic disorders, with more
than 250 million affected people worldwide in 2001
(http://www.who.org).
Underlying the irreversibility of hearing loss in
mammals is the inability to replace lost hair cells by cell
division and by regeneration from endogenous cells in the
inner-ear epithelia. Hearing impairment in humans is, in
most cases, a direct consequence of hair-cell loss. Clinically,
the functionality of lost hair cells can be partially
restored by the electrical stimulation of the auditory
nerve, which is achieved by the implantation of electronic
devices. For example, cochlear implants can provide a
subset of suitable patients with improved hearing. Other
avenues of therapy are being explored to find more
biologically based and more widely applicable treatments.
The past year has introduced stem cells into the search
for new approaches to hair-cell regeneration in mammals.
A major advance in the prospects for the use of stem cells
for the replacement of inner-ear cells came with the recent
discovery that hair cells could be generated in vivo from
embryonic stem (ES) cells, from adult inner-ear stem cells
and from neural stem cells [3–5]. These stem cells are
pluripotent, such that all cell types in the inner ear can, in
theory, be regenerated from these cells. We propose that
stem-cell-based treatment regimens might be applicable to
the damaged inner ear as part of future clinical applications
for the treatment of hearing loss.
Stem cells for the treatment of degenerative diseases
Cell-replacement therapywith stem cellshas the potential to
have a massive impact on human health during the coming
decades. The first targets for therapeutic stem-cell applications
are degenerative ailments, such as heart disease,
diabetes, Parkinson’s disease and other neurodegenerative
disorders. The initial results using stem-cell-based generation
of replacement cells for these disorders indicate that
stem cells can be developed into highly specialized cell types
and that these new cells can function in animal models, even
improving the underlying organ function [6–9].
There are three principal sources for stem cells that
have been used to (re-)generate organ-specific cell types:
ES cells, stem cells that are isolated from the organ to be
generated and stem cells from other organs. Consequently,
the regeneration of lost hair cells can, theoretically, involve
ES cells, inner-ear stem cells or stem cells from brain, skin
or the hematopoietic system.
Hair cells from embryonic stem cells
ES cells are derived from the inner cell mass of the
blastocyst. Because they are the precursors for all other
embryonic cells, ES cells have the greatest capacity for
differentiation into multiple cell types, which is termed
pluripotency. ES cells also have the capacity for selfrenewal
and can, therefore, be expanded to large numbers.
The generation of specific cell types by directing ES-cell
differentiation hypothetically offers an extensive resource
for developing clinical applications to replace diseased
or injured cells. Successful application of this strategy
appears to validate this hypothesis, because it has led to
Corresponding author: Stefan Heller (hellers@epl.meei.harvard.edu).
Available online 17 June 2004
Opinion TRENDS in Molecular Medicine Vol.10 No.7 July 2004
www.sciencedirect.com 1471-4914/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.molmed.2004.05.008
the generation of dopaminergic neurons for Parkinson’s
disease [6,8], motor neurons for spinal-cord injuries [10]
and, apparently, insulin-secreting cells for diabetes [7]
(but see [11]). Recently, inner-ear progenitors have been
generated from murine ES cells in vitro [4]. These progenitors
express a set of marker genes that identify them
as cells in the lineage of the hair cells, because these
markers can only be found in this specific combination in
the developing inner ear. After differentiation in vitro, a
subpopulation of the ES-cell-derived progenitors exhibited
a hair-cell phenotype, as revealed by the expression of
characteristic markers such as the transcription factors
Math1 (murine atonal homologue 1) and Brn3.1, which are
important for the generation of, and for maintaining the
maturation of, hair cells [12,13]. Expression of these
transcriptional key regulators was accompanied by the
upregulation of structural hair-cell proteins, such as
the unconventional myosin VIIA [14,15], parvalbumin 3
[16,17] and espin [18,19].
The implantation of genetically labeled ES-cell-derived
inner-ear progenitors into the inner ear of chicken embryos
and following their fate through early otic development
showed that engrafted cells initiated the expression of
hair-cell markers when situated in developing inner-ear
sensory epithelia. Progenitor-derived cells that were
found elsewhere in the inner ear did not express haircell
markers. Consequently, it has been hypothesized that
grafted murine ES-cell-derived inner-ear progenitor cells
can respond to local cues that control (hair) cell-type
specification in the developing chicken inner ear [4].
Although the developing avian inner-ear sensory epithelia
are different from injured or diseased mammalian organ
of Corti or vestibular hair-cell-bearing epithelia, these
results are the first successful approach using ES cells to
generate hair cells in vivo.
Hair cells from adult stem cells
Stem cells have been isolated and propagated from
many adult organs, including the brain, bone marrow,
muscle, heart, skin, eye and, recently, from the inner ear
[3,9,20–23]. Neural stem cells, which have the ability to
differentiate into many neuronal cell types, have been
successfully grafted into the drug-injured mouse inner
ear; the cells survived for several weeks and expressed
markers of mature cell types, including glia, neurons and
hair cells, albeit not in the cochlea [5,24]. Comparison of
the in vitro potential of adult neural stem cells with stem
cells from the inner ear of adult mice revealed two
substantial differences in the potential of the cells to
differentiate into hair-cell-marker-positive cells [3]. First,
the upregulation of hair-cell markers was readily observed
in ,10% of all cells that were differentiated from innerear-derived
stem cells in vitro, whereas adult neural stem
cells that were isolated from the forebrain rarely (,0.1%)
gave rise to hair-cell-marker-positive cells in this assay.
Second, inner-ear stem cells appeared to differentiate
more completely into hair cells than the neural stem-cell
derivatives. This became apparent by the formation of
hair-bundle-like structures that were immunopositive
for specific stereociliary markers (Figure 1k) [3]. In vitro
inner-ear stem-cell-derived cells, after transplantation
into a developing chicken inner ear, upregulate hair-cellspecific
markers in a similar manner to grafted ES-cellderivatives
[3,4].
Adult inner-ear stem cells reside in the sensory epithelium
of the utricle [3] and are a plausible candidate for
the progenitor cells that have been postulated as the
source of hair-cell regeneration in the damaged utricular
sensory epithelium [25–29]. Inner-ear stem cells are
pluripotent because they can develop into many other
cell types outside of the inner ear that are derived from
either ectodermal, endodermal or mesodermal germ layers.
The defining stem-cell feature of inner-ear stem cells is
their high proliferative capacity, which makes it possible to
isolate these cells in the form of clonal floating colonies or
‘spheres’. Proliferation potential is crucial to developing
treatment strategies for hearing loss, because propagation
of these cells might become the foundation of a replacement
strategy for human inner-ear cells.
Do hair cells that are generated from stem cells follow the
native developmental program?
The variety of cellular interactions that have roles during
the complex development and morphogenesis of the inner
ear are
inner-ear disorders is to find a cure for the hearing loss
that is caused by the loss of cochlear hair cells or spiral
ganglion neurons. The recent discovery of stem cells in
the adult inner ear that are capable of differentiating
into hair cells, as well as the finding that embryonic
stem cells can be converted into hair cells, raise hope
for the future development of stem-cell-based treatment
regimens. Here, we propose different approaches
for using stem cells to regenerate the damaged inner
ear and we describe the potential obstacles that translational
approaches must overcome for the development
of stem-cell-based cell-replacement therapies for
the damaged inner ear.
The sense of hearing is integral to our interaction with our
environment, yet the cellular components of the inner ear
are vulnerable to a variety of damaging agents. All hearing
sensation is derived from the output of a remarkably small
number of sensory cells: fewer than 15 000 per inner ear.
These hair cells are the mechanoelectrical transducers of
the ear; deflections of the stereociliary bundles (the hairlike
structures that give hair cells their name) on their
apical surfaces lead to transmitter release from their
basolateral poles, leading, in turn, to action potentials in
the auditory nerve fibers.
Most types of congenital and acquired hearing loss arise
from damage to, or loss of, cochlear hair cells or their
associated neurons. The incidence of heritable deafness is
high: one child in a thousand is born deaf; another one in a
thousand becomes deaf before adulthood [1,2]. Depending
on the age of onset, hearing impairment can affect oral
language acquisition, cognitive development and psychosocial
development. The prevalence of acquired hearing
loss is rising, as the population of the world increases
and ages and as noise pollution steadily increases. It is
estimated that one in three adults over the age of 65
has a handicapping hearing loss, making this condition
one of the most common chronic disorders, with more
than 250 million affected people worldwide in 2001
(http://www.who.org).
Underlying the irreversibility of hearing loss in
mammals is the inability to replace lost hair cells by cell
division and by regeneration from endogenous cells in the
inner-ear epithelia. Hearing impairment in humans is, in
most cases, a direct consequence of hair-cell loss. Clinically,
the functionality of lost hair cells can be partially
restored by the electrical stimulation of the auditory
nerve, which is achieved by the implantation of electronic
devices. For example, cochlear implants can provide a
subset of suitable patients with improved hearing. Other
avenues of therapy are being explored to find more
biologically based and more widely applicable treatments.
The past year has introduced stem cells into the search
for new approaches to hair-cell regeneration in mammals.
A major advance in the prospects for the use of stem cells
for the replacement of inner-ear cells came with the recent
discovery that hair cells could be generated in vivo from
embryonic stem (ES) cells, from adult inner-ear stem cells
and from neural stem cells [3–5]. These stem cells are
pluripotent, such that all cell types in the inner ear can, in
theory, be regenerated from these cells. We propose that
stem-cell-based treatment regimens might be applicable to
the damaged inner ear as part of future clinical applications
for the treatment of hearing loss.
Stem cells for the treatment of degenerative diseases
Cell-replacement therapywith stem cellshas the potential to
have a massive impact on human health during the coming
decades. The first targets for therapeutic stem-cell applications
are degenerative ailments, such as heart disease,
diabetes, Parkinson’s disease and other neurodegenerative
disorders. The initial results using stem-cell-based generation
of replacement cells for these disorders indicate that
stem cells can be developed into highly specialized cell types
and that these new cells can function in animal models, even
improving the underlying organ function [6–9].
There are three principal sources for stem cells that
have been used to (re-)generate organ-specific cell types:
ES cells, stem cells that are isolated from the organ to be
generated and stem cells from other organs. Consequently,
the regeneration of lost hair cells can, theoretically, involve
ES cells, inner-ear stem cells or stem cells from brain, skin
or the hematopoietic system.
Hair cells from embryonic stem cells
ES cells are derived from the inner cell mass of the
blastocyst. Because they are the precursors for all other
embryonic cells, ES cells have the greatest capacity for
differentiation into multiple cell types, which is termed
pluripotency. ES cells also have the capacity for selfrenewal
and can, therefore, be expanded to large numbers.
The generation of specific cell types by directing ES-cell
differentiation hypothetically offers an extensive resource
for developing clinical applications to replace diseased
or injured cells. Successful application of this strategy
appears to validate this hypothesis, because it has led to
Corresponding author: Stefan Heller (hellers@epl.meei.harvard.edu).
Available online 17 June 2004
Opinion TRENDS in Molecular Medicine Vol.10 No.7 July 2004
www.sciencedirect.com 1471-4914/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.molmed.2004.05.008
the generation of dopaminergic neurons for Parkinson’s
disease [6,8], motor neurons for spinal-cord injuries [10]
and, apparently, insulin-secreting cells for diabetes [7]
(but see [11]). Recently, inner-ear progenitors have been
generated from murine ES cells in vitro [4]. These progenitors
express a set of marker genes that identify them
as cells in the lineage of the hair cells, because these
markers can only be found in this specific combination in
the developing inner ear. After differentiation in vitro, a
subpopulation of the ES-cell-derived progenitors exhibited
a hair-cell phenotype, as revealed by the expression of
characteristic markers such as the transcription factors
Math1 (murine atonal homologue 1) and Brn3.1, which are
important for the generation of, and for maintaining the
maturation of, hair cells [12,13]. Expression of these
transcriptional key regulators was accompanied by the
upregulation of structural hair-cell proteins, such as
the unconventional myosin VIIA [14,15], parvalbumin 3
[16,17] and espin [18,19].
The implantation of genetically labeled ES-cell-derived
inner-ear progenitors into the inner ear of chicken embryos
and following their fate through early otic development
showed that engrafted cells initiated the expression of
hair-cell markers when situated in developing inner-ear
sensory epithelia. Progenitor-derived cells that were
found elsewhere in the inner ear did not express haircell
markers. Consequently, it has been hypothesized that
grafted murine ES-cell-derived inner-ear progenitor cells
can respond to local cues that control (hair) cell-type
specification in the developing chicken inner ear [4].
Although the developing avian inner-ear sensory epithelia
are different from injured or diseased mammalian organ
of Corti or vestibular hair-cell-bearing epithelia, these
results are the first successful approach using ES cells to
generate hair cells in vivo.
Hair cells from adult stem cells
Stem cells have been isolated and propagated from
many adult organs, including the brain, bone marrow,
muscle, heart, skin, eye and, recently, from the inner ear
[3,9,20–23]. Neural stem cells, which have the ability to
differentiate into many neuronal cell types, have been
successfully grafted into the drug-injured mouse inner
ear; the cells survived for several weeks and expressed
markers of mature cell types, including glia, neurons and
hair cells, albeit not in the cochlea [5,24]. Comparison of
the in vitro potential of adult neural stem cells with stem
cells from the inner ear of adult mice revealed two
substantial differences in the potential of the cells to
differentiate into hair-cell-marker-positive cells [3]. First,
the upregulation of hair-cell markers was readily observed
in ,10% of all cells that were differentiated from innerear-derived
stem cells in vitro, whereas adult neural stem
cells that were isolated from the forebrain rarely (,0.1%)
gave rise to hair-cell-marker-positive cells in this assay.
Second, inner-ear stem cells appeared to differentiate
more completely into hair cells than the neural stem-cell
derivatives. This became apparent by the formation of
hair-bundle-like structures that were immunopositive
for specific stereociliary markers (Figure 1k) [3]. In vitro
inner-ear stem-cell-derived cells, after transplantation
into a developing chicken inner ear, upregulate hair-cellspecific
markers in a similar manner to grafted ES-cellderivatives
[3,4].
Adult inner-ear stem cells reside in the sensory epithelium
of the utricle [3] and are a plausible candidate for
the progenitor cells that have been postulated as the
source of hair-cell regeneration in the damaged utricular
sensory epithelium [25–29]. Inner-ear stem cells are
pluripotent because they can develop into many other
cell types outside of the inner ear that are derived from
either ectodermal, endodermal or mesodermal germ layers.
The defining stem-cell feature of inner-ear stem cells is
their high proliferative capacity, which makes it possible to
isolate these cells in the form of clonal floating colonies or
‘spheres’. Proliferation potential is crucial to developing
treatment strategies for hearing loss, because propagation
of these cells might become the foundation of a replacement
strategy for human inner-ear cells.
Do hair cells that are generated from stem cells follow the
native developmental program?
The variety of cellular interactions that have roles during
the complex development and morphogenesis of the inner
ear are
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واحدة من أكبر التحديات في معالجةاضطرابات الإذن الداخلية لإيجاد علاج لفقدان السمعالذي يسببه فقدان خلايا الشعر cochlear أو دوامةالعقدة العصبية. الاكتشاف الأخير للخلايا الجذعية فيالإذن الداخلية الكبار التي قادرة على التمييز بينإلى خلايا الشعر، فضلا عن إيجاد هذا الجنينيةخلايا جذعية يمكن تحويلها إلى خلايا الشعر، ورفع الأملللتنمية المستقبلية لعلاج يستند إلى الخلية الجذعيةالأنظمة العلاجية. هنا، فإننا نقترح نهجاً مختلفةلاستخدام الخلايا الجذعية لتجديد الداخلية التالفةالإذن، ووصف العقبات المحتملة أن متعديةويجب التغلب على النهج لتطويرمن العلاجات المستندة إلى الخلية الجذعية خلية-استبدالالإذن الداخلية تالفة.حاسة السمع جزء لا يتجزأ من تفاعلنا مع موقعناالبيئة، ومع ذلك المكونات الخلوية للإذن الداخليةمعرضون لمجموعة متنوعة من العوامل الضارة. استماع جميعالإحساس مشتق من إخراج شكل ملحوظ صغيرةعدد الخلايا الحسية: أقل من 15 000 في الإذن الداخلية.من هذه الخلايا الشعر محولات ميتشانويليكتريكال منالإذن؛ أو الحزم ستيريوسيلياري (hairlikeالهياكل التي تعطي خلايا الشعر اسم) على ماالأسطح قمي يؤدي إلى الإفراج عن مرسل من بهمأقطاب باسولاتيرال، مما يؤدي، بدوره، إلى إمكانات العمل فيألياف العصب السمعي.تنشأ معظم أنواع فقدان السمع الخلقية والمكتسبةمن تلف أو فقدان خلايا الشعر cochlear أو بهمالخلايا العصبية المرتبطة بها. معدل الإصابة بالصمم الموروثةعالية: ولادة طفل واحد في الألف الصم؛ واحد آخر فيألف يصبح الصم قبل بلوغ سن الرشد [1، 2]. يعتمدعمر البدء، يمكن أن يؤثر ضعف السمع على الفماكتساب اللغة، والنمو المعرفي والنفسي والاجتماعيالتنمية. انتشار السمع المكتسبةارتفاع الخسائر، كسكان الزيادات العالميةوالإعمار ويزيد باطراد التلوث الضوضائي. إنه من دواعي سرورييقدر أن واحداً من ثلاثة بالغين فوق سن ال 65وقد فقدان السمع المعوقة، مما يجعل هذا الشرطواحدة من الاضطرابات المزمنة الأكثر شيوعاً، المزيدالمتضررة من 250 مليون شخص في العالم في عام 2001(http://www.who.org.)الكامنة وراء عدم الرجوع عن فقدان السمع فيالثدييات هي عدم القدرة على استبدال خلايا الشعر المفقودة بالخليةشعبة ومن التجدد من الخلايا الذاتية فيابيثيليا الإذن الداخلية. ضعف السمع لدى البشر،معظم الحالات، كنتيجة مباشرة لفقدان خلايا الشعر. سريرياً،يمكن أن يكون الأداء الوظيفي لفقدان الشعر الخلايا جزئيااستعادة بواسطة التحفيز الكهربائي للسمعالعصب، الذي يتحقق من خلال غرس الإلكترونيةالأجهزة. على سبيل المثال، يمكن أن توفر عملية زرع cochlearمجموعة فرعية مرضى مناسبة مع تحسين السمع. الأخرىويجري استكشاف سبل العلاج العثور على المزيدالعلاجات أساس بيولوجيا وقابلة للتطبيق على نطاق أوسع.العام الماضي أدخلت الخلايا الجذعية في البحثلنهج جديدة لتجديد خلايا الشعر في الثدييات.تقدما كبيرا في احتمالات استخدام الخلايا الجذعيةلاستبدال خلايا الإذن الداخلية وجاء مع الأخيرةاكتشاف أن خلايا الشعر يمكن أن تتولد في فيفو منالخلايا الجذعية الجنينية (ES)، من الخلايا الجذعية البالغة الإذن الداخليةوتنبع من العصبية خلايا [3-5]. من هذه الخلايا الجذعيةpluripotent، مثل كافة الخلية أنواع في الإذن الداخلية يمكن أن،من الناحية النظرية، يمكن إعادة إنشائها من هذه الخلايا. ونحن نقترح أنيمكن تطبيقها لنظم العلاج القائمة على الخلايا الجذعيةتلف الإذن الداخلية كجزء من التطبيقات السريرية مستقبلالعلاج فقدان السمع.الخلايا الجذعية لعلاج الأمراض التنكسيةثيرابيويث استبدال الخلية الجذعية سيلشاس القدرة علىيكون له تأثير كبير على صحة الإنسان خلال القادمةالعقود. الأهداف الأولى لتطبيقات الخلايا الجذعية العلاجيةهي الأمراض التنكسية، مثل أمراض القلب،مرض السكري ومرض باركنسون وغيرها الأعصاباضطرابات. النتائج الأولية باستخدام الجيل يستند إلى الخلية الجذعيةلاستبدال خلايا لهذه الاضطرابات تشير إلى أنويمكن وضع الخلايا الجذعية في أنواع الخلايا المتخصصة للغايةوأن هذه الخلايا الجديدة يمكن أن تعمل في نماذج حيوانية، حتىتحسين وظيفة الجهاز الأساسي [6-9].وهناك ثلاثة مصادر رئيسية للخلايا الجذعية التيوقد استخدمت على (إعادة) إنشاء أنواع الخلايا الخاصة بالجهاز:دإط الخلايا، الخلايا الجذعية المعزولة من الجهاز لتكونالتي تم إنشاؤها، والخلايا الجذعية من الأجهزة الأخرى. ونتيجة لذلك،يمكن، من الناحية النظرية، تنطوي على تجديد خلايا الشعر المفقودةدإط الخلايا أو الخلايا الجذعية الإذن الداخلية أو الخلايا الجذعية من الدماغ، والجلدأو نظام المكونة للدم.خلايا الشعر من الخلايا الجذعية الجنينيةدإط الخلايا المشتقة من كتلة الخلايا الداخليةالكيسة. لأنهم على السلائف لسائرالخلايا الجنينية، دإط الخلايا لها قدرة أكبر علىالتمايز إلى أنواع متعددة من الخلايا، وهو ما يسمىبلوريبوتينسي. دإط الخلايا أيضا لديها القدرة على سيلفرينيوالويمكن، لذلك، يمكن توسيعها لإعداد كبيرة.توليد أنواع خلية معينة عن طريق توجيه دإط-الخليةالتفريق نظرياً يوفر موارد الواسعةلتطوير التطبيقات السريرية ليحل محل المريضةأو الخلايا المتضررة. التطبيق الناجح لهذه الاستراتيجيةويبدو أن التحقق من صحة هذه الفرضية، لأن ذلك قد أدى إلىالكاتب المقابلة: Stefan هيلر (البند hellers@epl.meei.harvard.edu).متاح على الإنترنت 17 يونيو 2004اتجاهات الرأي في الطب الجزيئي Vol.10 رقم 7 تموز/يوليه 2004www.sciencedirect.com 1471-4914/$-انظر مسألة الجبهة س 2004 السفير المحدودة. جميع الحقوق محفوظة. doi:10.1016/j.molmed.2004.05.008توليد الخلايا العصبية تتميز عن باركنسونمرض [6,8]، الخلايا العصبية الحركية لإصابات النخاع الشوكي [10]ويبدو أن إفراز الأنسولين الخلايا لمرضى السكري [7](ولكن انظر [11]). في الآونة الأخيرة، كانت فروعه الإذن الداخليةولدت من مورين دإط الخلايا في المختبر [4]. هذه موروثالتعبير عن مجموعة من الجينات ماركر أن التعرف عليهاكما الخلايا في نسب خلايا الشعر، نظراً لأن هذهيمكن فقط الاطلاع على علامات في هذه التركيبة المحددة فيالإذن الداخلية النامية. وبعد التمايز في المختبر،أظهرت يتدنى فروعه المستمدة من الخلية ESالنمط الظاهري خلايا شعر، كما يتضح من التعبير عنعلامات مميزة مثل عوامل النسخMath1 (مورين المناظرة واهن 1) و Brn3.1،هامة لتوليد، والحفاظ علىنضج، خلايا الشعر [12، 13]. التعبير عن هذهورافق النسخي المنظمين الرئيسيينupregulation بروتينات خلايا الشعر الهيكلية، مثلالميوسين غير تقليدية VIIA [14,15]، بارفالبومين 3[16,17] و [18,19] إسبن.غرس وراثيا المسمى مشتقة دإط-الخليةموروث الإذن الداخلية في الإذن الداخلية لاجنة الدجاجوفي أعقاب مصيرهم من خلال الإسراع بتطوير أوتيكوأظهرت أن الخلايا انجرافتيد شرعت في التعبير عنعلامات خلية الشعر عندما يقع في وضع الإذن الداخليةابيثيليا الحسية. الخلايا المستمدة من السلف التي كانتيتم العثور على أي مكان آخر في الإذن الداخلية لا تعبر عن هايرسيلعلامات. ونتيجة لذلك، فقد كان الافتراض بأنالمطعمة خلايا الإذن الداخلية السلف موريني مشتقة دإط-الخليةويمكن الرد على الرموز المحلية التي تتحكم في نوع الخلية (الشعر)مواصفات في الإذن الداخلية الدجاج النامي [4].ورغم أن إنفلونزا الطيور النامية من ابيثيليا الحسية الإذن الداخليةتختلف عن الجهاز الثدييات المتضررة أو المريضةof Corti or vestibular hair-cell-bearing epithelia, theseresults are the first successful approach using ES cells togenerate hair cells in vivo.Hair cells from adult stem cellsStem cells have been isolated and propagated frommany adult organs, including the brain, bone marrow,muscle, heart, skin, eye and, recently, from the inner ear[3,9,20–23]. Neural stem cells, which have the ability todifferentiate into many neuronal cell types, have beensuccessfully grafted into the drug-injured mouse innerear; the cells survived for several weeks and expressedmarkers of mature cell types, including glia, neurons andhair cells, albeit not in the cochlea [5,24]. Comparison ofthe in vitro potential of adult neural stem cells with stemcells from the inner ear of adult mice revealed twosubstantial differences in the potential of the cells todifferentiate into hair-cell-marker-positive cells [3]. First,the upregulation of hair-cell markers was readily observedin ,10% of all cells that were differentiated from innerear-derivedstem cells in vitro, whereas adult neural stemcells that were isolated from the forebrain rarely (,0.1%)gave rise to hair-cell-marker-positive cells in this assay.Second, inner-ear stem cells appeared to differentiatemore completely into hair cells than the neural stem-cellderivatives. This became apparent by the formation ofhair-bundle-like structures that were immunopositivefor specific stereociliary markers (Figure 1k) [3]. In vitroinner-ear stem-cell-derived cells, after transplantationinto a developing chicken inner ear, upregulate hair-cellspecificmarkers in a similar manner to grafted ES-cellderivatives[3,4].Adult inner-ear stem cells reside in the sensory epitheliumof the utricle [3] and are a plausible candidate forthe progenitor cells that have been postulated as thesource of hair-cell regeneration in the damaged utricularsensory epithelium [25–29]. Inner-ear stem cells arepluripotent because they can develop into many othercell types outside of the inner ear that are derived fromeither ectodermal, endodermal or mesodermal germ layers.The defining stem-cell feature of inner-ear stem cells istheir high proliferative capacity, which makes it possible toisolate these cells in the form of clonal floating colonies or‘spheres’. Proliferation potential is crucial to developingtreatment strategies for hearing loss, because propagationof these cells might become the foundation of a replacementstrategy for human inner-ear cells.Do hair cells that are generated from stem cells follow thenative developmental program?The variety of cellular interactions that have roles duringthe complex development and morphogenesis of the innerear are
يجري ترجمتها، يرجى الانتظار ..
واحدة من أكبر التحديات في معالجة اضطرابات
الأذن الداخلية هو البحث عن علاج فقدان السمع
ان سببها هو فقدان خلايا الشعر أو قوقعة حلزونية
العقدة العصبية.وإن اكتشاف الخلايا الجذعية في الكبار
في خلايا الشعر في الأذن الداخلية التي هي قادرة على التمييز، فضلا عن العثور على هذا جنيني
يمكن تحويل الخلايا الجذعية إلى خلايا الشعر، تثير الأمل
بالنسبة لمستقبل تطور الخلايا الجذعية على أساس العلاج
بالحمية.وهنا نقترح اتباع نهج مختلفة
لاستخدام الخلايا الجذعية تجديد معطوب
الأذن الداخلية و وصف لنا العقبات المحتملة أن التصدع
النهج يجب التغلب عليها من أجل تطوير
من الخلايا الجذعية تقوم علاجات استبدال الخلايا التالفة في الأذن الداخلية
-
إن حاسة السمع هي جزء لا يتجزأ من تفاعلنا مع شركائنا
البيئة، ومع ذلك فإن المكونات الخلوية من الأذن الداخلية
معرضة للعديد من العوامل الضارة.جميع السمع
الإحساس مستمد من الناتج صغير ملحوظ
عدد الخلايا الحسية: اقل من 15 الف في الأذن الداخلية -
هذه خلايا الشعر mechanoelectrical محولات
الأذن؛ والانحرافات stereociliary حزم (hairlike
الأذن الداخلية هو البحث عن علاج فقدان السمع
ان سببها هو فقدان خلايا الشعر أو قوقعة حلزونية
العقدة العصبية.وإن اكتشاف الخلايا الجذعية في الكبار
في خلايا الشعر في الأذن الداخلية التي هي قادرة على التمييز، فضلا عن العثور على هذا جنيني
يمكن تحويل الخلايا الجذعية إلى خلايا الشعر، تثير الأمل
بالنسبة لمستقبل تطور الخلايا الجذعية على أساس العلاج
بالحمية.وهنا نقترح اتباع نهج مختلفة
لاستخدام الخلايا الجذعية تجديد معطوب
الأذن الداخلية و وصف لنا العقبات المحتملة أن التصدع
النهج يجب التغلب عليها من أجل تطوير
من الخلايا الجذعية تقوم علاجات استبدال الخلايا التالفة في الأذن الداخلية
-
إن حاسة السمع هي جزء لا يتجزأ من تفاعلنا مع شركائنا
البيئة، ومع ذلك فإن المكونات الخلوية من الأذن الداخلية
معرضة للعديد من العوامل الضارة.جميع السمع
الإحساس مستمد من الناتج صغير ملحوظ
عدد الخلايا الحسية: اقل من 15 الف في الأذن الداخلية -
هذه خلايا الشعر mechanoelectrical محولات
الأذن؛ والانحرافات stereociliary حزم (hairlike
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لغات أخرى
دعم الترجمة أداة: الآيسلندية, الأذرية, الأردية, الأفريقانية, الألبانية, الألمانية, الأمهرية, الأوديا (الأوريا), الأوزبكية, الأوكرانية, الأويغورية, الأيرلندية, الإسبانية, الإستونية, الإنجليزية, الإندونيسية, الإيطالية, الإيغبو, الارمنية, الاسبرانتو, الاسكتلندية الغالية, الباسكية, الباشتوية, البرتغالية, البلغارية, البنجابية, البنغالية, البورمية, البوسنية, البولندية, البيلاروسية, التاميلية, التايلاندية, التتارية, التركمانية, التركية, التشيكية, التعرّف التلقائي على اللغة, التيلوجو, الجاليكية, الجاوية, الجورجية, الخؤوصا, الخميرية, الدانماركية, الروسية, الرومانية, الزولوية, الساموانية, الساندينيزية, السلوفاكية, السلوفينية, السندية, السنهالية, السواحيلية, السويدية, السيبيوانية, السيسوتو, الشونا, الصربية, الصومالية, الصينية, الطاجيكي, العبرية, العربية, الغوجراتية, الفارسية, الفرنسية, الفريزية, الفلبينية, الفنلندية, الفيتنامية, القطلونية, القيرغيزية, الكازاكي, الكانادا, الكردية, الكرواتية, الكشف التلقائي, الكورسيكي, الكورية, الكينيارواندية, اللاتفية, اللاتينية, اللاوو, اللغة الكريولية الهايتية, اللوكسمبورغية, الليتوانية, المالايالامية, المالطيّة, الماورية, المدغشقرية, المقدونية, الملايو, المنغولية, المهراتية, النرويجية, النيبالية, الهمونجية, الهندية, الهنغارية, الهوسا, الهولندية, الويلزية, اليورباية, اليونانية, الييدية, تشيتشوا, كلينجون, لغة هاواي, ياباني, لغة الترجمة.
- Password contains an invalid character.
- By Roberta L. Duyff, MS, RD, FADA, CFCSf
- So muxx
- Password contains an invalid character.
- شكرا على قبول الصداقه
- الخبرة
- مرحلة التصفيات
- تسلم
- اريد ان اكبر
- Ridículo
- Fine very well
- انا اك عجبتن و نتي
- العام التالى
- التعليم حق للسوريين
- هذا هو الحب
- Password contains an invalid character.
- يرتدي
- fat shaming
- انا ااريد ان تثق بي طول الوقت
- Meu amor senti tanto tua falta nao te pa
- داة مخلينى احبك
- Tenth
- By Roberta L. Duyff, MS, RD, FADA, CFCSf
- شكرا يا ولد عمي
