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Journal of Biomedical Materials... May 2016Acquiring adequate number of cells is one of the crucial factors to apply tissue engineering strategies in order to recover critical-sized defects. While the... (Review)
Review
Acquiring adequate number of cells is one of the crucial factors to apply tissue engineering strategies in order to recover critical-sized defects. While the reprogramming technology used for inducing pluripotent stem cells (iPSCs) opened up a direct path for generating pluripotent stem cells, a direct conversion strategy may provide another possibility to obtain desired cells for tissue engineering. In order to convert a somatic cell into any other cell type, diverse approaches have been investigated. Conspicuously, in contrast to traditional viral transduction method, non-viral delivery of conversion factors has the merit of lowering immune responses and provides safer genetic manipulation, thus revolutionizing the generation of directly converted cells and its application in therapeutics. In addition, applying various microenvironmental modulations have potential to ameliorate the conversion of somatic cells into different lineages. In this review, we discuss the recent progress in direct conversion technologies, specifically focusing on generating mesenchymal cell types.
Topics: Animals; Cellular Reprogramming Techniques; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Stem Cell Niche; Tissue Engineering
PubMed: 26729213
DOI: 10.1002/jbm.b.33601 -
Scientific Reports Mar 2017Dentin sialoprotein (DSP) is a dentin extracellular matrix protein. It is involved in dental mesenchymal cell lineages and dentin formation through regulation of its...
Dentin sialoprotein (DSP) is a dentin extracellular matrix protein. It is involved in dental mesenchymal cell lineages and dentin formation through regulation of its target gene expression. DSP mutations cause dentin genetic diseases. However, mechanisms of DSP in controlling dental mesenchymal cell differentiation are unknown. Using DSP as bait, we screened a protein library from mouse odontoblastic cells and found that DSP is a ligand and binds to cell surface receptor, occludin. Further study identified that the C-terminal DSP domain interacts with the occludin extracellular loop 2. The C-terminal DSP domain induced phosphorylation of occludin Ser and focal adhesion kinase (FAK) Ser and Tyr. Coexpression of DSP, occludin and FAK was detected in dental mesenchymal cells during tooth development. Occludin physically interacts with FAK, and occludin and FAK phosphorylation can be blocked by DSP and occludin antibodies. This DSP domain facilitates dental mesenchymal cell differentiation and mineralization. Furthermore, transplantation and pulp-capping procedures revealed that this DSP domain induces endogenous dental pulp mesenchymal cell proliferation, differentiation and migration, while stimulating blood vessel proliferation. This study elucidates the mechanism of DSP in dental mesenchymal lineages and implies that DSP may serve as a therapeutic agent for dentin-pulp complex regeneration in dental caries.
Topics: Animals; Cell Differentiation; Dentin; Extracellular Matrix Proteins; Focal Adhesion Kinase 1; Mesenchymal Stem Cells; Mice; Occludin; Phosphoproteins; Phosphorylation; Protein Binding; Protein Interaction Mapping; Protein Processing, Post-Translational; Sialoglycoproteins
PubMed: 28331230
DOI: 10.1038/s41598-017-00339-w -
The American Journal of Pathology Mar 2018In vitro models for the investigation of renal vascular development are limited. We previously showed that isolated metanephric mesenchymal (MM) and ureteric bud (UB)...
In vitro models for the investigation of renal vascular development are limited. We previously showed that isolated metanephric mesenchymal (MM) and ureteric bud (UB) cells grown in three-dimensional (3D) matrices formed organoids that consisted of primitive vascular structures surrounding a polarized epithelium. Here, we examined the potential of two principal effectors of vasculogenesis, vascular endothelial growth factor A (VEGF-A), and platelet-derived growth factor B chain (PDGF-BB), to stimulate MM cell differentiation. The results showed that MM cells possess angioblast characteristics by expressing phenotypic markers for endothelial and mesenchymal cells. UB cells synthesize VEGF-A and PDGF-BB proteins and RNA, whereas the MM cells express the respective cognate receptors, supporting their role in directional induction of vasculogenesis. VEGF-A stimulated proliferation of MM cells in monolayer and in 3D sponges but did not affect MM cell migration, organization, or vasculogenesis. However, PDGF-BB stimulated MM cell proliferation, migration, and vasculogenesis in monolayer and organization of the cells into primitive capillary-like assemblies in 3D sea sponge scaffolds in vitro. A role for PDGF-BB in vasculogenesis in the 3D MM/UB co-culture system was validated by direct interference with PDGF-BB or PDGF receptor-β cell interactions to implicate PDGF-BB as a primary effector of MM cell vasculogenesis. Thus, MM cells resemble early renal angioblasts that may provide an ideal platform for the investigation of renal vasculogenesis in vitro.
Topics: Animals; Becaplermin; Cell Movement; Cell Proliferation; Cells, Cultured; Mesenchymal Stem Cells; Mice; Neovascularization, Physiologic; Vascular Endothelial Growth Factor A
PubMed: 29269120
DOI: 10.1016/j.ajpath.2017.10.022 -
Medecine Sciences : M/S Mar 2011
Topics: Cell Differentiation; Mesenchymal Stem Cells
PubMed: 21568121
DOI: 10.1051/medsci/2011273227 -
Scientific Reports Jun 2019Human mesenchymal stem (hMSCs) are defined as multi-potent colony-forming cells expressing a specific subset of plasma membrane markers when grown on flat tissue culture...
Human mesenchymal stem (hMSCs) are defined as multi-potent colony-forming cells expressing a specific subset of plasma membrane markers when grown on flat tissue culture polystyrene. However, as soon as hMSCs are used for transplantation, they are exposed to a 3D environment, which can strongly impact cell physiology and influence proliferation, differentiation and metabolism. Strategies to control in vivo hMSC behavior, for instance in stem cell transplantation or cancer treatment, are skewed by the un-physiological flatness of the standard well plates. Even though it is common knowledge that cells behave differently in vitro compared to in vivo, only little is known about the underlying adaptation processes. Here, we used micrometer-scale defined surface topographies as a model to describe the phenotype of hMSCs during this adaptation to their new environment. We used well established techniques to compare hMSCs cultured on flat and topographically enhanced polystyreneand observed dramatically changed cell morphologies accompanied by shrinkage of cytoplasm and nucleus, a decreased overall cellular metabolism, and slower cell cycle progression resulting in a lower proliferation rate in cells exposed to surface topographies. We hypothesized that this reduction in proliferation rate effects their sensitivity to certain cancer drugs, which was confirmed by higher survival rate of hMSCs cultured on topographies exposed to paclitaxel. Thus, micro-topographies can be used as a model system to mimic the natural cell micro-environment, and be a powerful tool to optimize cell treatment in vitro.
Topics: Adaptation, Physiological; Aged; Cell Cycle; Cell Shape; Cell Size; Female; Humans; Mesenchymal Stem Cells; Paclitaxel; Phenotype; Surface Properties
PubMed: 31235713
DOI: 10.1038/s41598-019-45284-y -
Best Practice & Research. Clinical... Feb 2016The discovery of mesenchymal stem cells (MSCs) in perinatal sources, such as the amniotic fluid (AF) and the umbilical connective tissue, the so-called Wharton's jelly... (Review)
Review
The discovery of mesenchymal stem cells (MSCs) in perinatal sources, such as the amniotic fluid (AF) and the umbilical connective tissue, the so-called Wharton's jelly (WJ), has transformed them into promising stem cell grafts for the application in regenerative medicine. The advantages of AF-MSCs and WJ-MSCs over adult MSCs, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), include their minimally invasive isolation procedure, their more primitive cell character without being tumourigenic, their low immunogenicity and their potential autologous application in congenital disorders and when cryopreserved in adulthood. This chapter gives an overview of the biology of AF-MSCs and WJ-MSCs, and their regenerative potential based on the results of recent preclinical and clinical studies. In the end, open questions concerning the use of WJ-MSCs and AF-MSCs in regenerative medicine will be emphasized.
Topics: Amniotic Fluid; Animals; Brain Diseases; Cell Differentiation; Cell Movement; Diabetes Mellitus; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regeneration; Skin; Skin Physiological Phenomena; Wharton Jelly
PubMed: 26482184
DOI: 10.1016/j.bpobgyn.2015.07.006 -
Vox Sanguinis Jul 2004
Review
Topics: Animals; Blood Component Removal; Cell Differentiation; Cytokines; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Immunophenotyping; Mesenchymal Stem Cells; Stem Cells
PubMed: 15209876
DOI: 10.1111/j.1741-6892.2004.00452.x -
Oxidative Medicine and Cellular... 2017Mesenchymal stem cells (MSCs) are multipotent cells that are currently being investigated in a wide variety of clinical trials for their anti-inflammatory and...
Mesenchymal stem cells (MSCs) are multipotent cells that are currently being investigated in a wide variety of clinical trials for their anti-inflammatory and immunomodulatory properties as well as their osteogenic and chondrogenic capabilities. However, there are considerable interdonor variability and heterogeneity of MSC populations, making it challenging to compare different products. Furthermore, proliferation, differentiation, and immunomodulation of MSCs decrease with aging and ex vivo expansion. The sirtuins have emerged as a class of protein deacylases involved in aging, oxidative stress, and metabolism. Sirtuin 3 (SIRT3) is the major mitochondrial deacetylase involved in reducing oxidative stress while preserving oxidative metabolism, and its levels have been shown to decrease with age. This study investigated the role of SIRT3 in MSC differentiation and aging. As MSCs were expanded ex vivo, SIRT3 levels decreased. In addition, SIRT3 depletion reduced MSC differentiation into adipocytes and osteoblasts. Furthermore, overexpression of SIRT3 in later-passage MSCs reduced aging-related senescence, reduced oxidative stress, and enhanced their ability to differentiate. These data suggest that overexpressing SIRT3 might represent a strategy to increase the quality and quantity of MSCs utilized for clinical applications.
Topics: Cell Differentiation; Cellular Senescence; Humans; Immunophenotyping; Mesenchymal Stem Cells; Sirtuin 3
PubMed: 28717408
DOI: 10.1155/2017/5841716 -
Advances in Experimental Medicine and... 2018Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem... (Review)
Review
Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis - supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great therapeutic potential in cancer therapy, as well as stem cell exosome and/or microvesicle-mediated tissue regeneration. In this review, the use of hMSCs in stem cell-mediated cancer therapy is discussed.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasms
PubMed: 28730382
DOI: 10.1007/5584_2017_64 -
Journal of Interferon & Cytokine... Oct 2021Infection is the leading cause of admission and mortality in neonatal intensive care units. Immature immune function and antibiotic resistance make the treatment more... (Review)
Review
Infection is the leading cause of admission and mortality in neonatal intensive care units. Immature immune function and antibiotic resistance make the treatment more difficult. However, there is no effective prevention for it. Recently, more and more researches are focusing on stem cell therapy, especially mesenchymal stem cells (MSCs); their potential paracrine effect confer MSCs with a major advantage to treat the immune and inflammatory disorders associated with neonatal infection. In this review, we summarize the basal properties and preclinical evidence of MSCs and explore the potential mechanisms of paracrine factors of MSCs for neonatal infection.
Topics: Animals; Humans; Infections; Mesenchymal Stem Cells
PubMed: 34672801
DOI: 10.1089/jir.2021.0094