scholarly journals Pharmacological Retention of Oral Mucosa Progenitor/Stem Cells

2009 ◽  
Vol 88 (12) ◽  
pp. 1113-1118 ◽  
Author(s):  
K. Izumi ◽  
K. Inoki ◽  
Y. Fujimori ◽  
C.L. Marcelo ◽  
S.E. Feinberg
Keyword(s):  
Stem Cells ◽  
Cell Size ◽  
Oral Mucosa ◽  
Cell Population ◽  
Mammalian Target Of Rapamycin ◽  
Specific Inhibitor ◽  
Proliferative Potential ◽  
Oral Keratinocytes ◽  
Ability To Regenerate

Oral mucosa progenitor/stem cells reside as a small-sized cell population that eventually differentiates concurrently with an increase in cell size. Activation of the mammalian target of rapamycin (mTOR) leads to an increase in cell size. We hypothesized that rapamycin, a specific inhibitor of mTOR, will maintain primary human oral keratinocytes as a small-sized, undifferentiated cell population capable of retaining their proliferative capacity. Primary, rapamycin-treated (2 nM, 20 nM) oral keratinocytes showed a diminished cell size that correlated with a higher clonogenicity, a longer-term proliferative potential, and a slower cycling cell population concurrent with decreased expression of a differentiation marker when compared with untreated cells. Only the 2-nM rapamycin-treated oral keratinocytes maintained their ability to regenerate oral mucosa in vitro after 15 weeks of culture. Rapamycin, a Food and Drug Administration-approved drug, may have applicability for use in creating a highly proliferative cell population for use in regenerative medicine.

Isolation of Human Oral Keratinocyte Progenitor/Stem Cells

2007 ◽  
Vol 86 (4) ◽  
pp. 341-346 ◽  
Author(s):  
K. Izumi ◽  
T. Tobita ◽  
S.E. Feinberg
Keyword(s):  
Stem Cells ◽  
Cell Population ◽  
Proliferative Potential ◽  
Peroxisome Proliferator ◽  
Oral Keratinocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ability To Regenerate ◽  
Forming Efficiency ◽  
Stem Cell Populations

Progenitor/stem cell populations of epithelium are known to reside in the small-sized cell population. Our objective was to physically isolate and characterize an oral keratinocyte-enriched population of small-sized progenitor/stem cells. Primary human oral mucosal keratinocytes cultured in a chemically defined serum-free culture system, devoid of animal-derived feeder cells, were sorted by relative cell size and characterized by immunolabeling for β1 integrin, nuclear transcription factor, peroxisome proliferator-activated receptor-gamma, and cell-cycle analysis. Sorted cells were distinguished as progenitor/stem cells by functional assays and their ability to regenerate an oral mucosal graft. Small-sized cells demonstrated the lowest expression of peroxisome proliferator-activated receptor-gamma, the highest colony-forming efficiency, a longer long-term proliferative potential, an enriched quiescent cell population, and the ability to regenerate an oral mucosal graft, implying that the small-sized cultured oral keratinocytes contained an enriched population of progenitor/stem cells.

scholarly journals A Preliminary Study of Constructing Tissue Engineered Oral Mucosa

2021 ◽  
Author(s):  
Qin Zhang ◽  
Yu-Jing Tian ◽  
Tao Ding ◽  
De-Hong Femg
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Small Intestine ◽  
Oral Mucosa ◽  
Porous Membrane ◽  
Adipose Derived Stem Cells ◽  
Oral Keratinocytes ◽  
Cell Scaffold ◽  
Compound Graft

Abstract Background: Adipose derived stem cells (ADSCs) have a great potential for tissue-engineering purposes, and they may be introduced in oral mucosa tissue engineering for urethroplasty. This study was aim to develop a tissue-engineered oral mucosa through seeding oral keratinocytes (OKs) and adipose derived stem cells (ADSCs) on small intestine submucosa (SIS). Methods: SIS was obtained from porcine small intestine, and OKs and ADSCs were obtained from canine sources and were cultured and expanded in vitro. The two cell lines were seeded on the two surfaces of the SIS, and the cell-scaffold compound graft was cultured in an air fluid level for 1 week.Results: The SIS exhibited a porous membrane, and no cells were found through HE staining. The model cultured with OK-SIS only formed a thin and loose epithelium. Whereas the model cultured with OK-SIS-ADSC was much thicker and denser. Conclusion: The co-cultured of ADSC and OK grew well on the SIS in which the OKs formed a multilayer of epithelium. So it is feasible to construct a tissue-engineered oral mucosa graft with ADSCs, OKs and SIS. The ADSCs contribute to a thicker epithelium formation.

scholarly journals A Preliminary Study of Constructing Tissue Engineered Oral Mucosa

2021 ◽  
Vol 7 (6) ◽  
Author(s):  
Zhang Q ◽  
Tian YJ ◽  
Ding T ◽  
Feng DH
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Small Intestine ◽  
Oral Mucosa ◽  
Porous Membrane ◽  
Adipose Derived Stem Cells ◽  
Oral Keratinocytes ◽  
Cell Scaffold ◽  
Compound Graft

Adipose derived stem cells (ADSCs) have a great potential for tissue-engineering purposes, and they may be introduced in oral mucosa tissue engineering for urethroplasty. This study was aimed to develop a tissue-engineered oral mucosa through seeding oral keratinocytes (OKs) and adipose derived stem cells (ADSCs) on small intestine submucosa (SIS). From August 2018 to October 2019, an observational study was conducted in the laboratory of our hospital, to develop a tissue-engineered oral mucosa.SIS was obtained from porcine small intestine, and OKs and ADSCs were obtained from canine sources and were cultured and expanded in vitro. The two cell lines were seeded on the two surfaces of the SIS, and the cell-scaffold compound graft was cultured in an air fluid level for 1 week. The SIS exhibited a porous membrane, and no cells were found through HE staining. The model cultured with OK-SIS only formed a thin and loose epithelium. Whereas the model cultured with OK-SIS-ADSC was much thicker and denser. The co-cultured of ADSC and OK grew well on the SIS in which the OKs formed a multilayer of epithelium. So it is feasible to construct a tissue-engineered oral mucosa graft with ADSCs, OKs and SIS. The ADSCs contribute to a thicker epithelium formation.

Characteristics of homogeneously small keratinocytes from newborn rat skin: possible epidermal stem cells

1991 ◽  
Vol 261 (6) ◽  
pp. C964-C972 ◽  
Author(s):  
J. H. Pavlovitch ◽  
M. Rizk-Rabin ◽  
P. Jaffray ◽  
H. Hoehn ◽  
M. Poot
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Population ◽  
Calcium Binding ◽  
Small Cells ◽  
Proliferative Potential ◽  
Rat Skin ◽  
Newborn Rat ◽  
Basal Keratinocytes

The aims of the present study were to characterize the phenotype, growth kinetics, and proliferative activation in culture of a population of poorly differentiated homogeneously small (HS) keratinocytes. These slow-cycling cells were separated by unit gravity sedimentation from a population of actively proliferating basal keratinocytes in newborn rat skin. This population (approximately 1% of the total basal keratinocytes) consisted of extremely small cells with little cytoplasm or RNA. Their positive KL4 staining demonstrates that they were keratinocytes. HS keratinocytes did not, however, contain epidermal calcium binding protein. Acridine orange, bivariate Hoechst, and ethidium bromide flow cytometry of in vitro bromodeoxyuridine-labeled cells as well as Ki67 staining showed that HS keratinocytes were in the G0 stage of the cell cycle and did not actively proliferate in vivo. [3H]thymidine label-retaining cells were found only in the HS cell population, showing that HS cells may originate from a central position in the epidermal proliferative unit. Growth of HS cells in vitro was characterized by a delayed but progressive increase in RNA before entry into the cell cycle. The clonogenic efficiency of HS cells in primary culture was much less than that of larger cells. Subclones of HS cell colonies exceeded primary colonies in their cloning efficiency and proliferative potential, suggesting that HS cells, although normally prevented from dividing, retain a high self-renewal capacity. They also maintain the ability to differentiate. The results are consistent with the concept that HS cell population may represent the epidermal-specific progenitor cells which act as stem cells in this tissue.

Stem Cells Derived from Human Exfoliated Deciduous teeth [shed] in Neuronal Disorders: A Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Minu Anoop ◽  
Indrani Datta
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Dental Pulp ◽  
Therapeutic Potential ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Proliferative Potential ◽  
Pulp Tissue ◽  
Human Exfoliated Deciduous Teeth

: Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell‐based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.

In vitro cultured autologous pre-confluent oral keratinocytes for experimental prefabrication of oral mucosa

2004 ◽  
Vol 33 (5) ◽  
pp. 476-485 ◽  
Author(s):  
S Schultze-Mosgau ◽  
B.-K Lee ◽  
J Ries ◽  
K Amann ◽  
J Wiltfang
Keyword(s):  
Oral Mucosa ◽  
Oral Keratinocytes

scholarly journals Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis

2021 ◽  
Author(s):  
meng li ◽  
ning yang ◽  
li hao ◽  
wei zhou ◽  
lei li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
High Dose ◽  
Treatment Pathways ◽  
Marrow Mesenchymal Stem Cells

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

scholarly journals Hematopoietic stem/progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4773-4777 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Man-Ryul Lee ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Nutan Prasain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Induced Pluripotent

Abstract Cryopreservation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) is crucial for cord blood (CB) banking and transplantation. We evaluated recovery of functional HPC cryopreserved as mononuclear or unseparated cells for up to 23.5 years compared with prefreeze values of the same CB units. Highly efficient recovery (80%-100%) was apparent for granulocyte-macrophage and multipotential hematopoietic progenitors, although some collections had reproducible low recovery. Proliferative potential, response to multiple cytokines, and replating of HPC colonies was extensive. CD34+ cells isolated from CB cryopreserved for up to 21 years had long-term (≥ 6 month) engrafting capability in primary and secondary immunodeficient mice reflecting recovery of long-term repopulating, self-renewing HSCs. We recovered functionally responsive CD4+ and CD8+ T lymphocytes, generated induced pluripotent stem (iPS) cells with differentiation representing all 3 germ cell lineages in vitro and in vivo, and detected high proliferative endothelial colony forming cells, results of relevance to CB biology and banking.

scholarly journals Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4102-4109 ◽  
Author(s):  
CI Civin ◽  
G Almeida-Porada ◽  
MJ Lee ◽  
J Olweus ◽  
LW Terstappen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Population ◽  
Mononuclear Cells ◽  
Cell Subset ◽  
Fetal Sheep ◽  
Adult Human

Abstract Data from many laboratory and clinical investigations indicate that CD34+ cells comprise approximately 1% of human bone marrow (BM) mononuclear cells, including the progenitor cells of all the lymphohematopoietic lineages and lymphohematopoietic stem cells (stem cells). Because stem cells are an important but rare cell type in the CD34+ cell population, investigators have subdivided the CD34+ cell population to further enrich stem cells. The CD34+/CD38-cell subset comprises less than 10% of human CD34+ adult BM cells (equivalent to < 0.1% of marrow mononuclear cells), lacks lineage (lin) antigens, contains cells with in vitro replating capacity, and is predicted to be highly enriched for stem cells. The present investigation tested whether the CD34+/CD38-subset of adult human marrow generates human hematopoiesis after transfer to preimmune fetal sheep. CD34+/ CD38- cells purified from marrow using immunomagnetic microspheres or fluorescence-activated cell sorting generated easily detectable, long- term, multilineage human hematopoiesis in the human-fetal sheep in vivo model. In contrast, transfer of CD34+/CD38+ cells to preimmune fetal sheep generated only short-term human hematopoiesis, possibly suggesting that the CD34+/CD38+ cell population contains relatively early multipotent hematopoletic progenitor cells, but not stem cells. This work extends the prior in vitro evidence that the earliest cells in fetal and adult human marrow lack CD38 expression. In summary, the CD34+/ CD38-cell population has a high capacity for long-term multilineage hematopoietic engraftment, suggesting the presence of stem cells in this minor adult human marrow cell subset.

Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cells differentiated in vitro

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2740-2749 ◽  
Author(s):  
CD Helgason ◽  
G Sauvageau ◽  
HJ Lawrence ◽  
C Largman ◽  
RK Humphries
Keyword(s):  
Stem Cells ◽  
Es Cells ◽  
Hematopoietic Cells ◽  
Embryonic Stem ◽  
Homeobox Genes ◽  
Embryoid Bodies ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Differentiation And Proliferation

Little is known about the molecular mechanisms controlling primitive hematopoietic stem cells, especially during embryogenesis. Homeobox genes encode a family of transcription factors that have gained increasing attention as master regulators of developmental processes and recently have been implicated in the differentiation and proliferation of hematopoietic cells. Several Hox homeobox genes are now known to be differentially expressed in various subpopulations of human hematopoietic cells and one such gene, HOXB4, has recently been shown to positively determine the proliferative potential of primitive murine bone marrow cells, including cells with long-term repopulating ability. To determine if this gene might influence hematopoiesis at the earliest stages of development, embryonic stem (ES) cells were genetically modified by retroviral gene transfer to overexpress HOXB4 and the effect on their in vitro differentiation was examined. HOXB4 overexpression significantly increased the number of progenitors of mixed erythroid/myeloid colonies and definitive, but not primitive, erythroid colonies derived from embryoid bodies (EBs) at various stages after induction of differentiation. There appeared to be no significant effect on the generation of granulocytic or monocytic progenitors, nor on the efficiency of EB formation or growth rate. Analysis of mRNA from EBs derived from HOXB4-transduced ES cells on different days of primary differentiation showed a significant increase in adult beta-globin expression, with no detectable effect on GATA-1 or embryonic globin (beta H-1). Thus, HOXB4 enhances the erythropoietic, and possibly more primitive, hematopoietic differentiative potential of ES cells. These results provide new evidence implicating Hox genes in the control of very early stages in the development of the hematopoietic system and highlight the utility of the ES model for gaining insights into the molecular genetic regulation of differentiation and proliferation events.

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