Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration

Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.

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Induced Pluripotent Stem Cells in Dental and Nondental Tissue Regeneration: A Review of an Unexploited Potential

Stem Cells International ◽

10.1155/2020/1941629 ◽

2020 ◽

Vol 2020 ◽

pp. 1-24 ◽

Cited By ~ 2

Author(s):

Israa Ahmed Radwan ◽

Dina Rady ◽

Marwa M. S. Abbass ◽

Sara El Moshy ◽

Nermeen AbuBakr ◽

...

Keyword(s):

Stem Cells ◽

Regenerative Medicine ◽

Induced Pluripotent Stem Cells ◽

Tissue Regeneration ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Potential Applications ◽

Induced Pluripotent

Cell-based therapies currently represent the state of art for tissue regenerative treatment approaches for various diseases and disorders. Induced pluripotent stem cells (iPSCs), reprogrammed from adult somatic cells, using vectors carrying definite transcription factors, have manifested a breakthrough in regenerative medicine, relying on their pluripotent nature and ease of generation in large amounts from various dental and nondental tissues. In addition to their potential applications in regenerative medicine and dentistry, iPSCs can also be used in disease modeling and drug testing for personalized medicine. The current review discusses various techniques for the production of iPSC-derived osteogenic and odontogenic progenitors, the therapeutic applications of iPSCs, and their regenerative potential in vivo and in vitro. Through the present review, we aim to explore the potential applications of iPSCs in dental and nondental tissue regeneration and to highlight different protocols used for the generation of different tissues and cell lines from iPSCs.

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MicroRNAs: Crucial Players in the Differentiation of Human Pluripotent and Multipotent Stem Cells into Functional Hepatocyte-Like Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666211006102039 ◽

2021 ◽

Vol 16 ◽

Author(s):

Hao Xu ◽

Liying Wu ◽

Guojia Yuan ◽

Xiaolu Liang ◽

Xiaoguang Liu ◽

...

Keyword(s):

Stem Cells ◽

Liver Disease ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Critical Role ◽

Ectopic Expression ◽

Embryonic Stem ◽

The Body

: Hepatic disease negatively impacts liver function and metabolism. Primary human hepatocytes are the gold standard for the prediction and successful treatment of liver disease. However, the sources of hepatocytes for drug toxicity testing and disease modeling are limited. To overcome this issue, pluripotent stem cells (PSCs) have emerged as an alternative strategy for liver disease therapy. Human PSCs, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can self-renew and give rise to all cells of the body. Human PSCs are attractive cell sources for regenerative medicine, tissue engineering, drug discovery, and developmental studies. Several recent studies have shown that mesenchymal stem cells (MSCs) can also differentiate (or trans-differentiate) into hepatocytes. Differentiation of human PSCs and MSCs into functional hepatocyte-like cells (HLCs) opens new strategies to study genetic diseases, hepatotoxicity, infection of hepatotropic viruses, and analyze hepatic biology. Numerous in vitro and in vivo differentiation protocols have been established to obtain human PSCs/MSCs-derived HLCs and mimic their characteristics. It was recently discovered that microRNAs (miRNAs) play a critical role in controlling the ectopic expression of transcription factors and governing the hepatocyte differentiation of human PSCs and MSCs. In this review, we focused on the role of miRNAs in the differentiation of human PSCs and MSCs into hepatocytes.

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Constructing stem cell microenvironments using bioengineering approaches

Physiological Genomics ◽

10.1152/physiolgenomics.00099.2013 ◽

2013 ◽

Vol 45 (23) ◽

pp. 1123-1135 ◽

Cited By ~ 29

Author(s):

David A. Brafman

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Disease Modeling ◽

Mechanical Stimuli ◽

Culture Methods ◽

Stem Cell Fate ◽

And Function

Within the adult organism, stem cells reside in defined anatomical microenvironments called niches. These architecturally diverse microenvironments serve to balance stem cell self-renewal and differentiation. Proper regulation of this balance is instrumental to tissue repair and homeostasis, and any imbalance can potentially lead to diseases such as cancer. Within each of these microenvironments, a myriad of chemical and physical stimuli interact in a complex (synergistic or antagonistic) manner to tightly regulate stem cell fate. The in vitro replication of these in vivo microenvironments will be necessary for the application of stem cells for disease modeling, drug discovery, and regenerative medicine purposes. However, traditional reductionist approaches have only led to the generation of cell culture methods that poorly recapitulate the in vivo microenvironment. To that end, novel engineering and systems biology approaches have allowed for the investigation of the biological and mechanical stimuli that govern stem cell fate. In this review, the application of these technologies for the dissection of stem cell microenvironments will be analyzed. Moreover, the use of these engineering approaches to construct in vitro stem cell microenvironments that precisely control stem cell fate and function will be reviewed. Finally, the emerging trend of using high-throughput, combinatorial methods for the stepwise engineering of stem cell microenvironments will be explored.

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Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2015/305217 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 27

Author(s):

John Michel ◽

Matthew Penna ◽

Juan Kochen ◽

Herman Cheung

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tissue Regeneration ◽

Therapeutic Option ◽

Synthetic Polymers ◽

Review Article ◽

Osteogenic Lineage ◽

Wide Range

Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs forin vitroandin vivoexperiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years.

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Behavior of Mesenchymal Stem Cells Obtained From Dental Tissues: A Review of the Literature

Odovtos - International Journal of Dental Sciences ◽

10.15517/ijds.v21i1.34884 ◽

2019 ◽

Vol 21 (1) ◽

pp. 31-40

Author(s):

Mariné Ortiz-Magdaleno DDS, MSc, PhD ◽

Ana Isabel Romo-Tobías DDS ◽

Fernando Romo-Ramírez DDS, MSc ◽

Diana María Escobar DDS, MSc, PhD ◽

Héctor Flores-Reyes DDS, MSc, PhD ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Clinical Evidence ◽

Periodontal Regeneration ◽

In Vivo Studies ◽

Specific Cell ◽

Key Factors ◽

Dental Tissues

The success of tissue engineering in combination with tissue regeneration depends on the behavior and cellular activity in the biological processes developed within a structure that functions as a support, better known as scaffolds, or directly at the site of the injury. The cell-cell and cell-biomaterial interaction are key factors for the induction of a specific cell behavior, together with the bioactive factors that allow the formation of the desired tissue. Mesenchymal Stem Cells (MSC) can be isolated from the umbilical cord and bone marrow; however, the behavior of Dental Pulp Stem Cells (DPSC) has been shown to have a high potential for the formation of bone tissue, and these cells have even been able to induce the process of angiogenesis. Advances in periodontal regeneration, dentin-pulp complex, and craniofacial bone defects through the induction of MSC obtained from tooth structures in in vitro-in vivo studies have permitted the obtaining of clinical evidence of the achievements obtained to date.

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Human Organoids for Predictive Toxicology Research and Drug Development

Frontiers in Genetics ◽

10.3389/fgene.2021.767621 ◽

2021 ◽

Vol 12 ◽

Author(s):

Toshikatsu Matsui ◽

Tadahiro Shinozawa

Keyword(s):

Stem Cells ◽

Drug Development ◽

Disease Modeling ◽

Cell Types ◽

Underlying Disease ◽

Future Research ◽

Specific Cell ◽

Predictive Toxicology

Organoids are three-dimensional structures fabricated in vitro from pluripotent stem cells or adult tissue stem cells via a process of self-organization that results in the formation of organ-specific cell types. Human organoids are expected to mimic complex microenvironments and many of the in vivo physiological functions of relevant tissues, thus filling the translational gap between animals and humans and increasing our understanding of the mechanisms underlying disease and developmental processes. In the last decade, organoid research has attracted increasing attention in areas such as disease modeling, drug development, regenerative medicine, toxicology research, and personalized medicine. In particular, in the field of toxicology, where there are various traditional models, human organoids are expected to blaze a new path in future research by overcoming the current limitations, such as those related to differences in drug responses among species. Here, we discuss the potential usefulness, limitations, and future prospects of human liver, heart, kidney, gut, and brain organoids from the viewpoints of predictive toxicology research and drug development, providing cutting edge information on their fabrication methods and functional characteristics.

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Transcriptomically-guided mesendoderm induction of human pluripotent stem cells using a systematically defined culture scheme

10.1101/561068 ◽

2019 ◽

Author(s):

Richard L Carpenedo ◽

Sarah Y Kwon ◽

R Matthew Tanner ◽

Julien Yockell-Lelièvre ◽

Chandarong Choey ◽

...

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Cell Biology ◽

Disease Modeling ◽

Human Pluripotent Stem Cells ◽

Endoderm Differentiation ◽

Prolonged Differentiation ◽

Defined Culture

SummaryHuman pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation. After prolonged differentiation in vitro or in vivo, BA pre-treatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation.

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Hypes and Hopes of Stem Cell Therapies in Dentistry: a Review

Stem Cell Reviews and Reports ◽

10.1007/s12015-021-10326-4 ◽

2022 ◽

Author(s):

Alessandra Rodriguez y Baena ◽

Andrea Casasco ◽

Manuela Monti

Keyword(s):

Stem Cells ◽

Temporal Dynamics ◽

3D Cell Culture ◽

Basic Research ◽

Science Research ◽

Dental Stem Cells ◽

Exciting Field ◽

Cell Therapies

AbstractOne of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies. Graphical abstract

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