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Published Medical Research
| Dental Stem Cells
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| 01/04/2012 - Differentiation of dental pulp stem cells into islet-like aggregates.
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The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes.
Source - Stempeutics Research Malaysia Sdn Bhd, (773817-K), Lot G-E-2A, Enterprise 4, Technology Park Malaysia, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
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| 12/06/2011 - Dental Stem Cells Promote Spinal Cord Regeneration After Injury
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Recently,
a team of researchers at the Nagoya University Graduate School of
Medicine, motivated by the knowledge that stem cells taken from tooth
pulp are capable of stimulating long-term regeneration of nerves in
damaged spinal cords, tested the ability of dental stem cells to treat
said injuries. The results have positively demonstrated that dental stem
cells not only “promoted the regeneration of transected axons by
directly inhibiting multiple axon growth inhibitors,” but also,
“prevented a damage-induced apoptosis,” and were able to replaced the
original cells that were lost due to injury.
“To our knowledge,
the latter two neuroregenerative activities are unique to tooth-derived
stem cells and are not exhibited by any other previously described stem
cells,” the researchers stated. “We propose that tooth-derived stem
cells may be an excellent and practical cellular resource for the
treatment of SCI [spinal cord injury].”
The era of regenerative medicine is now.
To read the full article click here. |
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| 11/13/2011 - Stem cells in dental pulp of deciduous teeth
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Dental pulp from deciduous (baby) teeth, which are discarded after exfoliation, represents an advantageous source of young stem cells. Herein, we discuss the methods of Deciduous Teeth Stem Cells (DTSCs) isolation and cultivation. We show that based on these methods, at least three different stem cells populations can be identified: a population similar to bone marrow derived mesenchymal stem cells (BM-MSCs), an epithelial stem-like cells (ESCs) and/or a mixed population composed of both cell types. We analyzed the embryonic origin and stem
cell niche of DTSCs with respect to the advantages they can provide for
their future use in cell therapies and regenerative medicine. In vitro
and in vivo differentiation of the DTSCs populations, their
developmental potential, immunological compatibility, tissues
engineering, transplantation use in studies in animal models are also
the focus of the present report. We briefly describe the derivation of
induced pluripotent stem (iPS) cells from DTSCs, which can be obtained more easily and efficiently in comparison with human fibroblasts. These iPS cells
represent an interesting model for the investigation of pediatric
diseases and disorders. The importance of DTSCs banking is also
discussed.
Butantan, Genetics, av. Vital Brasil, 1500, São Paulo, Brazil, 05503-900, 55 11 3726 7222; ikerkis@butantan.gov.br. |
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| 10/28/2011 - Human dental pulp cells: a new source of cell therapy in a mouse model of compressive spinal cord injury.
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Programa
de Pesquisa em Neurociência Básica e Clínica, Instituto de Ciências
Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de
Janeiro, Brazil. Strategies
aimed at improving spinal cord regeneration after trauma are still
challenging neurologists and neuroscientists throughout the world. Many
cell-based therapies have been tested, with limited success in terms of
functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). These cells
present some advantages, such as the ease of the extraction process,
and expression of trophic factors and embryonic markers from both
ecto-mesenchymal and mesenchymal components. Young adult female C57/BL6
mice were subjected to laminectomy at T9 and compression of the spinal
cord with a vascular clip for 1?min. The cells
were transplanted 7 days or 28 days after the lesion, in order to
compare the recovery when treatment is applied in a subacute or chronic
phase. We performed quantitative analyses of white-matter preservation,
trophic-factor expression and quantification, and ultrastructural and
functional analysis. Our results for the HDPC-transplanted animals
showed better white-matter preservation than the DMEM groups, higher
levels of trophic-factor expression in the tissue, better tissue
organization, and the presence of many axons being myelinated by either
Schwann cells or
oligodendrocytes, in addition to the presence of some healthy-appearing
intact neurons with synapse contacts on their cell bodies. We also
demonstrated that HDPCs were able to express some glial markers such as
GFAP and S-100. The functional analysis also showed locomotor
improvement in these animals. Based on these findings, we propose that
HDPCs may be feasible candidates for therapeutic intervention after SCI
and central nervous system disorders in humans. |
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| 10/28/2011 - Feeder-free derivation of induced pluripotent stem cells from human immature dental pulp stem cells.
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Induced pluripotent stem cells
(iPSC) can be created by forcing expression of certain genes in
fibroblasts or other somatic cell types, reversing them to a pluripotent
state similar to that of embryonic stem cells (ESC). Here, we used human immature dental pulp stem cells
(hIDPSC) as an alternative source for creating iPSC. HIDPSC can be
easily isolated from accessible tissue of young and adult patients.
HIDPSC possess a fibroblast-like morphology, retaining characteristics
of adult multipotent stem cells.
Reprogramming of hIDPSC was fast, producing primary hIDPSC-iPSC
colonies even under feeder-free conditions. hIDPSC acquired ESC-like
morphology, expressed pluripotent markers, possessed stable, normal
karyotypes and demonstrate the ability to differentiated in vitro and in
vivo. Our data demonstrate that hIDPSC-iPSC offer an advantageous cell
system for future cell therapy and basic studies, particularly as a
model for pediatric developmental disorders. |
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| 09/03/2011 - Human dental pulp stem cells demonstrate better neural and epithelial stem cell properties than bone marrow-derived mesenchymal stem cells.
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Department of Stem Cell, Center for Stem
Cell and Gene Therapies Research and Practice, Institute of Health
Sciences, Kocaeli University, 41380, Kocaeli, Turkey,
ekaraoz@hotmail.com. Dental pulp stem cells
(hDP-SCs) were primarily derived from pulp tissues of primary incisors,
exfoliated deciduous and permanent third molar teeth. To understand the
characteristics of hDP-SCs from impacted third molar, proliferation
capacities, gene expression profiles, phenotypic, ultrastructural, and
differentiation characteristics were analyzed in comparison with human
bone marrow-derived mesenchymal stem cells (hBM-MSCs), extensively. hDP-SCs showed more developed and metabolically active cells.
Contrary to hBM-MSCs, hDP-SCs strongly expressed both cytokeratin
(CK)-18 and -19, which could involve in odontoblast differentiation and
dentine repair. The intrinsic neuro-glia characteristics of hDP-MSCs
were demonstrated by the expression of several specific transcripts and
proteins of neural stem cell and neurons. These cells
not only differentiate into adipogenic, osteogenic, and chondrogenic
lineage, but also share some special characteristics of expressing some
neural stem cell and epithelial
markers. Under defined conditions, hDP-SCs are able to differentiate
into both neural and vascular endothelial cells in vitro. Dental
pulp might provide an alternative source for human MSCs. hDP-SCs with a
promising differentiation capacity could be easily isolated, and
possible clinical use could be developed for neurodegenerative and oral
diseases in the future. |
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| 07/30/2011 - Differentiation and Neuro-Protective Properties of Immortalized Human Tooth Germ Stem Cells.
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Yalvaç ME, Yilmaz A, Mercan D, Aydin S, Dogan A, Arslan A, Demir Z, Salafutdinov II, Shafigullina AK, Sahin F, Rizvanov AA, Palotás A. Department
of Genetics and BioEngineering, College of Engineering and
Architecture, Yeditepe University, 26 Agustos Campus, Kayisdagi cad,
Kayisdagi, 34755, Istanbul, Turkey. Stem cells
are considered to be promising therapeutic options in many
neuro-degenerative diseases and injuries to the central nervous system,
including brain ischemia and spinal cord trauma. Apart from the gold
standard embryonic and mesenchymal origin, human tooth germ stem cells (hTGSCs) have also been shown to enjoy the characteristics of mesenchymal stem cells (MSCs) and the ability to differentiate into adipo-, chondro-, osteo- and neuro-genic cells, suggesting that they might serve as potential alternatives in the cellular therapy of various maladies. Immortalization of stem cells may be useful to avoid senescence of stem cells
and to increase their proliferation potential without altering their
natural characteristics. This study evaluated the expression of stem
cell markers, surface antigens, differentiation capacity, and karyotype
of hTGSCs that have been immortalized by human telomerase reverse
transcriptase (hTERT) or simian vacuolating virus 40 (SV40) large T
antigen. These undying cells were also evaluated for their
neuro-protective potential using an in vitro SH-SY5Y neuro-blastoma
model treated with hydrogen-peroxide or doxo-rubicin. Although
hTGSC-SV40 showed abnormal karyotypes, our results suggest that
hTGSC-hTERT preserve their MSC characteristics, differentiation capacity
and normal karyotype, and they also possess high proliferation rate and
neuro-protective effects even at great passage numbers. These peculiars
indicate that hTGSC-hTERT could be used as a viable model for studying
adipo-, osteo-, odonto- and neuro-genesis, as well as neuro-protection
of MSCs, which may serve as a springboard for potentially utilizing dental waste material in cellular therapy. |
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| 07/30/2011 - Isolation of pluripotent stem cells from human third molar dental pulp.
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Regenerative Medicine Laboratory, Universitat Internacional de Catalunya, Barcelona, Spain. Potent stem/progenitor cells have been isolated from normal human dental pulps, termed dental pulp stem cells (DPSCs). However, no study has described the presence of stem cell populations in human dental pulp from the third molar with embryonic phenotypes. The dental
pulp tissue was cultured in media with the presence of LIF, EGF, and
PDGF. In the present study, we describe a new population of pluripotent stem cells that were isolated from dental pulp (DPPSC). These cells
are SSEA-4+, Oct4+, Nanog+, FLK-1+, HNF3beta+, Nestin+, Sox2+, Lin28+,
c-Myc+, CD13+, CD105+, CD34-, CD45-, CD90low, CD29+, CD73low, STRO-1low
and CD146-. We have investigated by SEM analysis and q-RT-PCR the
capacity of DPPSCs to 3D differentiate in vitro using the Cell Carrier
3D glass scaffold into tissues that have similar characteristics to
embryonic mesoderm and endoderm layers. These data would support the use
of these cells, which are derived from an easily accessible
source and can be used in future regeneration protocols for many tissue
types that differentiate from the three embryonic layers. |
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| 07/30/2011 - Induced in vitro differentiation of neural-like cells from human exfoliated deciduous teeth-derived stem cells.
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Nourbakhsh N, Soleimani M, Taghipour Z, Karbalaie K, Mousavi SB, Talebi A, Nadali F, Tanhaei S, Kiyani GA, Nematollahi M, Rabiei F, Mardani M, Bahramiyan H, Torabinejad M, Nasr-Esfahani MH, Baharvand H. Pediatric
Department, School of Dentistry, 2Department of Anatomical Sciences,
School of Medicine, Isfahan University of Medical Sciences, Isfahan,
Iran. Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic and multipotent stem cells
with a neural crest cell origin. Additionally, they can be collected
with minimal invasiveness in comparison with other sources of
mesenchymal stem cells (MSCs). Therefore, SHED could be a
desirable option for potential therapeutic applications. In this study,
SHEDs were established from enzyme-disaggregated deciduous dental pulp obtained from 6 to 9 year-old children. The cells
had typical fibroblastoid morphology and expressed antigens
characteristic of MSCs, STRO1, CD146, CD45, CD90, CD106 and CD166, but
not the hematopoietic and endothelial markers, CD34 and CD31, as
assessed by FACS analysis. Differentiation assessment revealed a strong
osteogenic and adipogenic potential of SHEDs. In order to further
evaluate the in vitro differentiation potential of SHED into neural cells,
a simple short time growth factor-mediated induction was used.
Immunofluorescence staining and flow cytometric analysis revealed that
SHED rapidly expressed nestin and b-III tubulin, and later expressed
intermediate neural markers. In addition, the intensity and percentages
of nestin and b-III tubulin and mature neural markers (PSA-NCAM, NeuN,
Tau, TH, or GFAP) increased significantly following treatment. Moreover,
RT-PCR and Western blot analyses showed that the neural markers were
strongly up-regulated after induction. In conclusion, these results
provide evidence that SHED can differentiate into neural cells by the expression of a comprehensive set of genes and proteins that define neural-like cells in vitro. SHED cells
might be considered as new candidates for the autologous
transplantation of a wide variety of neurological diseases and
neurotraumatic injuries. |
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| 07/30/2011 - Pulp tissue from primary teeth: new source of stem cells.
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Department of Community Dentistry and Pediatric Dentistry, Dental School, Federal University of Bahia, Salvador, BA, Brazil. p-telles@uol.com.br SHED (stem cells from human exfoliated deciduous teeth) represent a population of postnatal stem cells capable of extensive proliferation and multipotential differentiation. Primary teeth may be an ideal source of postnatal stem cells
to regenerate tooth structures and bone, and possibly to treat neural
tissue injury or degenerative diseases. SHED are highly proliferative cells derived from an accessible tissue source, and therefore hold potential for providing enough cells for clinical applications. In this review, we describe the current knowledge about dental pulp stem cells
and discuss tissue engineering approaches that use SHED to replace
irreversibly inflamed or necrotic pulps with a healthy and functionally
competent tissue that is capable of forming new dentin. |
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| 05/01/2011 - Dual origin of mesenchymal stem cells contributing to organ growth and repair.
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Department
of Craniofacial Development and Comprehensive Biomedical Research
Centre, Dental Institute, Kings College London, London SE1 9RT, United
Kingdom. In many adult
tissues, mesenchymal stem cells (MSCs) are closely associated with
perivascular niches and coexpress many markers in common with pericytes.
The ability of pericytes to act as MSCs, however, remains
controversial. By using genetic lineage tracing, we show that some
pericytes differentiate into specialized tooth mesenchyme-derived
cells-odontoblasts-during tooth growth and in response to damage in
vivo. As the pericyte-derived mesenchymal cell contribution to
odontoblast differentiation does not account for all cell
differentiation, we identify an additional source of cells with MSC-like
properties that are stimulated to migrate toward areas of tissue damage
and differentiate into odontoblasts. Thus, although pericytes are
capable of acting as a source of MSCs and differentiating into cells of
mesenchymal origin, they do so alongside other MSCs of a nonpericyte
origin. This study identifies a dual origin of MSCs in a single tissue
and suggests that the pericyte contribution to MSC-derived mesenchymal
cells in any given tissue is variable and possibly dependent on the
extent of the vascularity. |
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| 03/08/2011 - 03/08/2011 - Type 1 diabetes stem cell treatment advances utilizing autologous dental stem cells
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by Doctor Dharmini Pathmanathan, DMD, PhD
Diabetes is a chronic degenerative disease of the beta-cells of the pancreas leading to a lifelong dependency on insulin treatments. While the cure for diabetes would be transplantation of cadaveric pancreatic islet cells to the diabetic individual, the scarcity of transplantable organs and side effects arising from a lifelong immunosuppressive regimen limits its therapeutic potential and is thus far from an ideal option. Similarly, the use of embryonic stem cells (ES), a favored option due to enormous differentiation potential of ES, is limited in its application in regenerative medicine because of persistent ethical and legal concerns. Thus, mesenchymal stem cells (MSCs) have been extensively studied for their ability to differentiate into insulin-producing cells. However, limited sources and the invasive procedures necessary to procure these cells restrict their application. Given the limitations of the above procedures, locating a source of MSCs that is readily available and accessible and without any significant donor morbidity would be an ideal solution. Recent article in the Journal of Dental Research presented a benchmark study in which dental pulp stem cells (DPSCs) were differentiated into functional pancreatic cells. DPSCs were isolated from deciduous teeth that were already planned for serial extraction as part of orthodontic management. In short, the DPSCs were differentiated to islet-like cell aggregates (ICAs) using various growth factors and their identity confirmed using expression studies. In vitro functional studies showing that the DPSCs differentiated into ICAs could indeed respond to a glucose challenge with insulin production provided further confirmation for their potential use in islet transplantation programs. These findings add to the body of evidence regarding DPSCs ability to be differentiated into pancreatic cell lineage and their potential as a source of human tissue that could be used for an autologous stem cell therapy for diabetes without fear of rejection. Since DPSCs do not have the same restrictions as ES, are readily accessible, can be harvested from the individual himself, and virtually eliminate the possibility of rejection and therefore the use of immunosuppressants, DPSCs are considered to be an ideal source for MSCs for emerging diabetes stem cell treatments. Beyond diabetes, these findings also validate and encourage the banking of dental pulp stem cells for use in autologous stem cell therapy.
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| 03/07/2011 - Vascular endothelial growth factor enhances in vitro proliferation and osteogenic differentiation of human dental pulp stem cells.
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J Biol Regul Homeost Agents. 2011 Jan-Mar;25(1):57-69. D' Alimonte I, Nargi E, Mastrangelo F, Falco G, Lanuti P, Marchisio M, Miscia S, Robuffo I, Capogreco M, Buccella S, Caputi S, Caciagli F, Tetè S, Ciccarelli R. Departments of Biomedical Sciences, University of Chieti, Italy Mesenchymal
stem cells (MSC), isolated from dental tissues, are largely studied for
future application in regenerative dentistry. In this study, we used
MSC obtained from human dental pulp (DPSC) of normal impacted third
molars that, when cultured in lineage-specific inducing media,
differentiate into osteoblasts and adipocytes (evaluated by Alizarin Red
S and Red Oil O stainings, respectively), thus showing a multipotency.
We confirmed that DPSC, grown under undifferentiating conditions, are
negative for hematopoietic (CD45, CD31, CD34, CD144) and positive for
mesenchymal (CD29, CD90, CD105, CD166, CD146, STRO-1) markers, that
underwent down-regulation when cells were grown in osteogenic medium for
3 weeks. In this condition, they also exhibit an increase in the
expression of osteogenic markers (RUNX-2, alkaline phosphatase) and
extracellular calcium deposition, whereas the expression of receptors
(VEGFR-1 and -2) for vascular endothelial growth factors (VEGF) and
related VEGF binding proteins was similar to that found in
undifferentiated DPSC. Exposure of DPSC growing under undifferentiating
or osteogenic conditions to VEGF-A165 peptide (10-40 ng/ml) for 8 days
dose- and time-dependently increased the number of proliferating cells
without inducing differentiation towards endothelial lineage, as
evaluated by the lack of expression of specific markers (CD31, CD34,
CD144). Additionally, exposure of DPSC cultured in osteogenic medium to
VEGF-A165 for a similar period enhanced cell differentiation towards
osteoblasts as evaluated after 14 and 21 days by Alizarin Red S staining
and alkaline phosphatase activity quantification. These findings may
have clinical implications possibly facilitating tissue repair and
remodeling. |
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| 03/07/2011 - Comparative Analysis of Telomere Length, Telomerase and Reverse Transcriptase Activity in Human Dental Stem Cells.
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Cell Transplant. 2011 Mar 8.
Byeong GJ, Kang EJ, Kumar BM, Maeng GH, Ock SA, Kwack DO, Park BW, Rho GJ. Stem
cells from dental tissues have been isolated and established for tooth
regenerative applications. However, basic characterization on their
biological properties still needs to be investigated before employing
them for effective clinical trials. In this study, we compared the
telomere length, relative telomerase activity ( RTA) and relative
reverse transcriptase activity ( RRA) as well as the surface antigen
profile and mesenchymal differentiation ability in human dental papilla
stem cells ( DPaSCs) , dental pulp stem cells ( DPuSCs) and dental
follicle stem cells ( DFSCs) with mesenchymal stem cells ( MSCs) derived
from bone marrow. Dental stem cells ( DSCs) were strongly positive for
cell surface markers, such as CD44 and CD90. However, slightly lower
expression of CD105 was observed in DPaSCs and DPuSCs compared to DFSCs
and MSCs. Following specific induction, DPaSCs, DFSCs and MSCs were
successfully differentiated into adipocytes and osteocytes. However,
DPuSCS, in particular, were able to differentiate into adipocytes but
failed to induce into osteogenic differentiation. Further, all DSCs,
MSCs, and MRC- 5 fibroblasts as control were investigated for telomere
length by non- radioactive chemiluminescent assay, RTA by relative-
quantitative telomerase repeat amplification protocol ( RQ- TRAP) , and
RRA by PCR- based assay. Mean telomere lengths in DPaSCs, DPuSCs, DFSCs
and MSCs was '11 kb, and the values did not differ significantly
(P<0.05) among the cells analyzed. RTA levels in DPaSCs were
significantly ( P<0. 05) higher than in MSCs, DPuSCs, DFSCs, and MRC-
5 fibroblasts and among DSCs, DFSCs showed a significantly ( P<0.
05) lower RTA. Moreover, RRA levels were significantly ( P<0. 05)
higher in DPaSCs, DPuSCs and MSCs than in DFSCs. Based on these
observations, we conclude that among DSCs, DPaSCs possessed ideal
characteristics on telomere length, telomerase activity and reverse
transcriptase ( RTase) activity, and may serve as suitable alternative
candidates for regenerative medicine. |
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| 03/01/2011 - Biomaterials coated by dental pulp cells as substrate for neural stem cell differentiation.
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Abstract
This
study is focused on the development of an in vitro hybrid system,
consisting in a polymeric biomaterial covered by a dental pulp cellular
stroma that acts as a scaffold offering a neurotrophic support for the
subsequent survival and differentiation of neural stem cells. In the
first place, the behavior of dental pulp stroma on the polymeric
biomaterial based on ethyl acrylate and hydroxy ethyl acrylate copolymer
was studied. For this purpose, cells from normal human third molars
were grown onto 0.5-mm-diameter biomaterial discs. After cell culture,
quantification of neurotrophic factors generated by the stromal cells
was performed by means of an ELISA assay. In the second place, survival
and differentiation of adult murine neural stem cells on the polymeric
biomaterials covered by dental pulp stromal cells was studied. The
results show the capacity of dental pulp cells to uniformly coat the
majority of the material's surface and to secrete neurotrophic factors
that become crucial for a subsequent differentiation of neural stem
cells. The use of stromal cells cultured on scaffolding biomaterials
provides neurotrophic pumps that may suggest new criteria for the design
of cell therapy experiments in animal models to assist the repair of
lesions in Central Nervous System. © 2011 Wiley Periodicals, Inc. J
Biomed Mater Res Part A:, 2011J Biomed Mater Res A. 2011 Feb 11. doi: 10.1002/jbm.a.33032. [Epub ahead of print]
Soria JM, Sancho-Tello M, Esparza MA, Mirabet V, Bagan JV, Monleón M, Carda C.
Facultad
Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avda Seminario
sn. 46113 Moncada, Valencia, Spain. jose.soria@uch.ceu.es. |
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| 01/25/2011 - Dental Stem Cells to regrow and repair Salivary Glands.
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By Doctor Dharmini Pathmanathan, DMD, PhD
Doctor Xing Yan, has been awarded a grant from the National Natural Science Foundation of China in the field of salivary gland regeneration utilizing dental stem cells. Dr. Yan will collaborate with Dr. George Huang, a StemSave Scientific Advisor on this important research project. The purpose of the research is to study the functional regeneration of salivary glands, specifically the parotid glands damaged by radiation, using induced pluripotent stem (iPS) cells reprogrammed from dental pulp stem cells. Salivary gland stem cells and iPS cells differentiated into salivary gland cells will be isolated and using animal models will be tested for their ability to regenerate a functional salivary gland.
While primary salivary gland tumors are rare, surgical and radiation treatments can have adverse consequences to salivary gland function. Annually, about 40,000 individuals are affected by radiation damage to the salivary glands secondary to head and neck cancer radiation therapy. Salivary gland hypofunction significantly compromises the quality of life of those individuals through poor oral health and neglect and non-compliance of drug treatments that reduce salivary flow. Options for those who suffer from salivary hypofunction are limited and at best palliative. Therefore, studies by Drs. Huang and Yan using dental stem cells to regenerate functional salivary glands are at the scientific forefront of finding real solutions to millions affected by poor salivary function. |
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| 01/24/2011 - Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures.
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Eur J Histochem. 2010 Nov 10;54(4):e46. Riccio M, Resca E, Maraldi T, Pisciotta A, Ferrari A, Bruzzesi G, De Pol A. Dept. Anatomy and Histology, University of Modena and Reggio Emilia. massimo.riccio@unimore.it. The
aim of this study was to characterize the in vitro osteogenic
differentiation of dental pulp stem cells (DPSCs) in 2D cultures and 3D
biomaterials. DPSCs, separated from dental pulp by enzymatic digestion,
and isolated by magnetic cell sorting were differentiated toward
osteogenic lineage on 2D surface by using an osteogenic medium. During
the differentiation process, DPSCs express specific bone proteins like
Runx-2, Osx, OPN and OCN with a sequential expression, analogous to
those occurring during osteoblast differentiation, and produce
extracellular calcium deposits. In order to differentiate cells in a 3D
space that mimes the physiological environment, DPSCs were cultured in
two distinct bioscaffolds, MatrigelTM and Collagen sponge. With the
addition of a third dimension, osteogenic differentiation and
mineralized extracellular matrix production significantly improved. In
particular, in MatrigelTM DPSCs differentiated with
osteoblast/osteocyte characteristics and connected by gap junction, and
therefore formed calcified nodules with a 3D intercellular network.
Furthermore, DPSCs differentiated in collagen sponge actively secrete
human type I collagen micro-fibrils and form calcified matrix
containing trabecular-like structures. These neo-formed DPSCs-scaffold
devices may be used in regenerative surgical applications in order to
resolve pathologies and traumas characterized by critical size bone
defects. |
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| 01/24/2011 - Integration of neuronally predifferentiated human dental pulp stem cells into rat brain in vivo.
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Neurochem Int. 2011 Jan 8.
Király M, Kádár K, Horváthy DB, Nardai P, Rácz GZ, Lacza Z, Varga G, Gerber G. Department of Oral Biology, Semmelweis University, Nagyvarad ter 4, 1089 Budapest, Hungary. AbstractPluripotency
and their neural crest origin make dental pulp stem cells (DPSCs) an
attractive donor source for neuronal cell replacement. Despite recent
encouraging results in this field, little is known about the
integration of transplanted DPSC derived neuronal pecursors into the
central nervous system. To address this issue, NFneuronally
predifferentiated DPSCs, labeled with a vital cell dye Vybrant DiD were
introduced into postnatal rat brain. DPSCs were transplanted into the
cerebrospinal fluid of 3-day-old male Wistar rats. Cortical lesion was
induced by touching a cold (-60°C) metal stamp to the calvaria over the
forelimb motor cortex. Four weeks later cell localization was detected
by fluorescent microscopy and neuronal cell markers were studied by
immunohistochemistry. To investigate electrophysiological properties of
engrafted, fluorescently labeled DPSCs, 300µm-thick horizontal brain
slices were prepared and the presence of voltage-dependent sodium and
potassium channels were recorded by patch clamping. Predifferentiated
donor DPSCs injected into the cerebrospinal fluid of newborn rats
migrated as single cells into a variety of brain regions. Most of the
cells were localized in the normal neural progenitor zones of the
brain, the subventricular zone (SVZ), subgranular zone (SGZ) and
subcallosal zone (SCZ). Immunohistochemical analysis revealed that
transplanted DPSCs expressed the early neuronal marker N-tubulin, the
neuronal specific intermediate filament protein NF-M, the postmitotic
neuronal marker NeuN, and glial GFAP. Moreover, the cells displayed TTX
sensitive voltage dependent (VD) sodium currents (I(Na)) and TEA
sensitive delayed rectifier potassium currents (K(DR)). Four weeks
after injury, fluorescently labeled cells were detected in the lesioned
cortex. Neurospecific marker expression was increased in DPSCs found in
the area of the cortical lesions compared to that in fluorescent cells
of uninjured brain. TTX sensitive VD sodium currents and TEA sensitive
K(DR) significantly increased in labeled cells of the cortically
injured area. In conclusion, our data demonstrate that engrafted
DPSC-derived cells integrate into the host brain and show neuronal
properties not only by expressing neuron-specific markers but also by
exhibiting voltage dependent sodium and potassium channels. This proof
of concept study reveals that predifferentiated hDPSCs may serve as
useful sources of neuro- and gliogenesis in vivo, especially when the
brain is injured. |
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| 01/24/2011 - Effect of platelet-rich plasma on dental stem cells derived from human impacted third molars.
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Regen Med. 2011 Jan;6(1):67-79. Lee UL, Jeon SH, Park JY, Choung PH. Department of Oral & Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, South Korea. AbstractAIM: Platelet-rich
plasma (PRP) is fabricated from autologous blood and extensively used
to promote soft and hard tissue healing. In the dental field,
autologous PRP is widely used combined with dental implant installation
and bone graft. This study will evaluate the biologic effect of PRP on
the proliferation and the differentiation of human dental stem cells,
and find the key cytokines inducing these effects to estimate the
clinical feasibility of PRP for dental tissue engineering. MATERIALS & METHODS: Venous
blood was obtained from four individuals and each PRP was fabricated.
The human dental stem cells were obtained from the periodontal ligament
(PDL) and dental pulp of the surgically extracted human third molars
and expanded in vitro. Immunocytochemical staining and flow cytometry
with STRO-1 and CD146 confirmed existence of mesenchymal stem cells in
the PDL and dental pulp. The effect of PRP on the proliferation of PDL
stem cells (PDLSCs) and dental pulp stem cells (DPSCs) was assessed by
colony-forming ability measurement,
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and
bromodeoxyuridine incorporation assay. Alkaline phosphatase activity
and calcium deposit were measured to evaluate the mineralization effect
of PRP PDLSCs and DPSCs. Alizarin red S staining was used to detect
mineral nodules. Odontogenic and osteogenic gene expressions were
evaluated in the PRP-treated PDLSCs and DPSCs by real-time quantitative
PCR. A protein array was performed to detect the key cytokines that
have an important role in the tissue regenerative effect of PRP. RESULTS: Flow
cytometry cell sorting showed that the cells from human PDL and dental
pulp contained mesenchymal stem cell populations. Colony-forming
ability and cellular proliferation of the dental stem cells were
increased at 0.5 and 1% PRP concentration but decreased at 5%
concentration. Long-term treatment with 1% PRP enhanced proliferation
of the human dental stem cells PDLSCs and DPSCs by 120 h and showed the
most significant enhancement at 96 h. PRP also promoted mineralization
differentiation of the two kinds of dental stem cells as shown by
measurement of alkaline phosphatase activity and calcium deposit under
mineralization conditioned media. Increased formation of mineral
nodules stained with alizarin red was observed in both PDLSCs and DPSCs
after treatment with 1% PRP. Real-time quantitative PCR showed higher
odontogenic and osteogenic gene expressions in PRP-treated PDLSCs and
DPSCs. RANTES/CCL5 and ICAM-1 were the two key cytokines that were
detected in human cytokine array with PRP. CONCLUSION: The
appropriate concentration of the PRP treatment enhanced proliferation
and mineralization differentiation of human dental stem cells.
RANTES/CCL5 and ICAM-1 might play an important role in PRP-induced
tissue regeneration but further study is needed to investigate the
whole mechanism. |
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| 12/12/2010 - Researchers at Boston University use stem cells to repair teeth
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Doctor George Huang discusses baby teeth and wisdom teeth as a potential source of stem cells that can be utilized in the treatment of disease and trauma.
By Doctor Alan A. Winter, DDS
Boston University Professor Doctor George Huang, the Herber
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