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International Journal of Molecular... Oct 2021Mesenchymal stromal cells (MSCs) have the capacity for self-renewal and multi-differentiation, and for this reason they are considered a potential cellular source in...
Mesenchymal stromal cells (MSCs) have the capacity for self-renewal and multi-differentiation, and for this reason they are considered a potential cellular source in regenerative medicine of cartilage and bone. However, research on this field is impaired by the predisposition of primary MSCs to senescence during culture expansion. Therefore, the aim of this study was to generate and characterize immortalized MSC (iMSC) lines from aged donors. Primary MSCs were immortalized by transduction of simian virus 40 large T antigen (SV40LT) and human telomerase reverse transcriptase (hTERT). Proliferation, senescence, phenotype and multi-differentiation potential of the resulting iMSC lines were analyzed. MSCs proliferate faster than primary MSCs, overcome senescence and are phenotypically similar to primary MSCs. Nevertheless, their multi-differentiation potential is unbalanced towards the osteogenic lineage. There are no clear differences between osteoarthritis (OA) and non-OA iMSCs in terms of proliferation, senescence, phenotype or differentiation potential. Primary MSCs obtained from elderly patients can be immortalized by transduction of SV40LT and hTERT. The high osteogenic potential of iMSCs converts them into an excellent cellular source to take part in in vitro models to study bone tissue engineering.
Topics: Aged; Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Proliferation; Cells, Cultured; Gene Expression; Humans; Immunohistochemistry; Mesenchymal Stem Cells; Osteogenesis; Telomerase; Tissue Donors; Transduction, Genetic
PubMed: 34639008
DOI: 10.3390/ijms221910667 -
Current Opinion in Hematology Nov 2006Our understanding of the biology and properties of mesenchymal stem cells or multipotent mesenchymal stromal cells has expanded dramatically over the last 3 years and is... (Review)
Review
PURPOSE OF REVIEW
Our understanding of the biology and properties of mesenchymal stem cells or multipotent mesenchymal stromal cells has expanded dramatically over the last 3 years and is likely to have an impact on clinical practice in the near future, making a review of this topic both timely and relevant
RECENT FINDINGS
Recommendations regarding nomenclature and the definition of mesenchymal stromal cells have been proposed, a rapidly dividing population within the mesenchymal stromal cell compartment has been better defined and the ability of these cells to exhibit characteristics of cells from a variety of lineages has been extended. The notion that tissue repair with mesenchymal stromal cells is related to transdifferentiation has been re-evaluated and, for the myocardium at least, may be due rather to a paracrine mechanism. The most dramatic developments have been in identifying some of the complex mechanisms underlying the immunosuppressive and nonimmunogenic properties of mesenchymal stromal cells which have important implications for the management of conditions like acute graft-versus-host disease.
SUMMARY
Mesenchymal stromal cells are a biologically important cell population that are able to support hematopoiesis, can differentiate along mesenchymal and nonmesenchymal lineages in vitro, are capable of suppressing alloresponses and appear to be nonimmunogenic. These properties suggest emerging roles for mesenchymal stromal cells in cell therapy.
Topics: Animals; Cell Differentiation; Graft vs Host Disease; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Stromal Cells; Terminology as Topic
PubMed: 17053453
DOI: 10.1097/01.moh.0000245697.54887.6f -
The Journal of Biological Chemistry Apr 2024Single-cell RNA-seq has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type....
Single-cell RNA-seq has led to novel designations for mesenchymal cells associated with bone as well as multiple designations for what appear to be the same cell type. The main goals of this study were to increase the amount of single-cell RNA sequence data for osteoblasts and osteocytes, to compare cells from the periosteum to those inside bone, and to clarify the major categories of cell types associated with murine bone. We created an atlas of murine bone-associated cells by harmonizing published datasets with in-house data from cells targeted by Osx1-Cre and Dmp1-Cre driver strains. Cells from periosteal bone were analyzed separately from those isolated from the endosteum and trabecular bone. Over 100,000 mesenchymal cells were mapped to reveal 11 major clusters designated fibro-1, fibro-2, chondrocytes, articular chondrocytes, tenocytes, adipo-Cxcl12 abundant reticular (CAR), osteo-CAR, preosteoblasts, osteoblasts, osteocytes, and osteo-X, the latter defined in part by periostin expression. Osteo-X, osteo-CAR, and preosteoblasts were closely associated with osteoblasts at the trabecular bone surface. Wnt16 was expressed in multiple cell types from the periosteum but not in cells from endocortical or cancellous bone. Fibro-2 cells, which express markers of stem cells, localized to the periosteum but not trabecular bone in adult mice. Suppressing bone remodeling eliminated osteoblasts and altered gene expression in preosteoblasts but did not change the abundance or location of osteo-X or osteo-CAR cells. These results provide a framework for identifying bone cell types in murine single-cell RNA-seq datasets and suggest that osteoblast progenitors reside near the surface of remodeling bone.
Topics: Animals; Mice; Chondrocytes; Mesenchymal Stem Cells; Osteoblasts; Osteocytes; Periosteum; Single-Cell Analysis; Mice, Inbred C57BL
PubMed: 38479598
DOI: 10.1016/j.jbc.2024.107158 -
Methods in Molecular Biology (Clifton,... 2021Mesenchymal-to-epithelial transition (MET) describes the ability of loosely associated migratory cells to form a more adherent sheet-like assembly of cells. MET is a...
Mesenchymal-to-epithelial transition (MET) describes the ability of loosely associated migratory cells to form a more adherent sheet-like assembly of cells. MET is a conserved motif occurring throughout organogenesis and plays a key role in regeneration and cancer metastasis, and is the first step in producing induced pluripotent stem cells (iPSCs). To resolve fundamental biological questions about MET, its relation to epithelial-to-mesenchymal transition, and to explore MET's role in tissue assembly and remodeling requires live models for MET that are amenable to experimentation. Many cases of clinically important MET are inferred since they occur deep with the body of the embryo or adult. We have developed a tractable model for MET, where cellular transitions can be directly observed under conditions where molecular, mechanical, and cellular contexts can be controlled experimentally. In this chapter, we introduce a 3-dimensional (3D) tissue model to study MET using Xenopus laevis embryonic mesenchymal cell aggregates.
Topics: Animals; Cell Movement; Cell Tracking; Ectoderm; Epithelial Cells; Imaging, Three-Dimensional; Mesenchymal Stem Cells; Mesoderm; Tissue Culture Techniques; Xenopus
PubMed: 32939727
DOI: 10.1007/978-1-0716-0779-4_21 -
Biomolecules Mar 2020Mesenchymal stem cells serve as the body's reservoir for healing and tissue regeneration. In cases of severe tissue trauma where there is also a need for tissue...
Mesenchymal stem cells serve as the body's reservoir for healing and tissue regeneration. In cases of severe tissue trauma where there is also a need for tissue organization, a scaffold may be of use to support the cells in the damaged tissue. Such a scaffold should be composed of a material that can biomimic the mechanical and biological properties of the target tissues in order to support autologous cell-adhesion, their proliferation, and differentiation. In this study, we developed and assayed a new biocomposite made of unique collagen fibers and alginate hydrogel that was assessed for the ability to support mesenchymal cell-proliferation and differentiation. Analysis over 11 weeks in vitro demonstrated that the scaffold was biocompatible and supports the cells viability and differentiation to produce tissue-like structures or become adipocyte under differentiation medium. When the biocomposite was enriched with nano particles (NPs), mesenchymal cells grew well after uptake of fluorescein isothiocyanate (FITC) labeled NPs, maintained their viability, migrated through the biocomposite, reached, and adhered to the tissue culture dish. These promising findings revealed that the scaffold supports the growth and differentiation of mesenchymal cells that demonstrate their full physiological function with no sign of material toxicity. The cells' functionality performance indicates and suggests that the scaffold is suitable to be developed as a new medical device that has the potential to support regeneration and the production of functional tissue.
Topics: 3T3-L1 Cells; Animals; Cell Differentiation; Cell Proliferation; Materials Testing; Mesenchymal Stem Cells; Mice; Tissue Scaffolds
PubMed: 32188110
DOI: 10.3390/biom10030458 -
Trends in Cell Biology Mar 2021Mesenchymal-epithelial crosstalk plays a crucial role in organ development and stem cell function. However, the identity of the mesenchymal cells involved in this... (Review)
Review
Mesenchymal-epithelial crosstalk plays a crucial role in organ development and stem cell function. However, the identity of the mesenchymal cells involved in this exchange was unclear. Recent significant advances in single-cell transcriptomics have defined the heterogeneity of these mesenchymal niches. By combining multiomic profiling, animal models, and organoid culture, new studies have not only demonstrated the roles of diverse mesenchymal cell populations but also defined the mechanisms underlying their regulation of niche signals. Focusing on several digestive organs, we describe how similar and diverse mesenchymal cell populations promote organ development and maintain proper stem cell activity, and how the heterogeneity of mesenchymal niches is altered in digestive diseases such as inflammation and cancer.
Topics: Animals; Homeostasis; Inflammation; Mesenchymal Stem Cells; Neoplasms; Stem Cells
PubMed: 33349527
DOI: 10.1016/j.tcb.2020.11.010 -
The Journal of Surgical Research Nov 2013Therapies using mesenchymal stem cells are a popular current avenue for development and utilization, especially in the fields of de novo tissue engineering... (Review)
Review
Therapies using mesenchymal stem cells are a popular current avenue for development and utilization, especially in the fields of de novo tissue engineering (Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000;164:247.) or tissue regeneration after physical injury (Kitoh H, Kitakoji T, Tsuchiya H, et al. Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis-a preliminary result of three cases. Bone 2004;35:892; Shumakov VI, Onishchenko NA, Rasulov MF, Krasheninnikov ME, Zaidenov VA. Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts. Bull Exp Biol Med 2003;136:192; Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J Cell Biochem 1994;56:283.). The osteogenic potential of these cells is of particular interest, given their recent usage for the closure of critical-sized bone defects and other nonhealing bone scenarios such as a nonunion. Recent literature suggests that inflammatory cytokines can significantly impact the osteogenic potential of these cells. A review of relevant, recent literature is presented regarding the impact of the inflammatory cascade on the osteogenic differentiation of these cells and how this varies across species. Finally, we identify areas of conflicting or absent evidence regarding the behavior of mesenchymal stem cells in response to inflammatory cytokines.
Topics: Animals; Bone Marrow Cells; Cell Differentiation; Cytokines; Humans; Inflammation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis
PubMed: 23972621
DOI: 10.1016/j.jss.2013.06.063 -
Cell Transplantation 2008Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. The lack of effective treatment and the characteristic of... (Review)
Review
Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. The lack of effective treatment and the characteristic of their pathology make these diseases appropriate candidates for cell therapy. Mesenchymal stem cells (MSCs) are multipotent stem-like cells that are capable of differentiating into mesenchymal and nonmesenchymal lineages. Their regenerative capacity after in vivo transplantation into animal models of neurodegenerative diseases has suggested that they could be useful against human diseases. Human bone marrow-derived MSCs (hMSCs) can be easily amplified in vitro and their transdifferentiation has been claimed in vitro and in vivo in neural cells. There are some doubts concerning the exact mechanisms responsible for the beneficial outcome observed after MSC transplantation into neurodegenerating tissues. Possible interpretations include cell replacement, trophic factor delivery, and immunomodulation. This review mainly concerns hMSCs transplantation in neurodegenerative diseases, because it has proven to be feasible, safe, and potentially effective. Although they have been used in hundreds of clinical trials, mixed results and no functional and long-lasting integration have so far been observed. hMSCs transplantations therefore still have their "dark side." However, the challenge in well-planned clinical trials merits discussion.
Topics: Animals; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neurodegenerative Diseases
PubMed: 19181205
DOI: 10.3727/096368908787236576 -
Expert Opinion on Biological Therapy Jan 2010Regulating stem cell contributions to vascularization is a challenging goal, but a fundamental aspect of regenerative medicine. Human mesenchymal stem cells retain... (Review)
Review
IMPORTANCE OF THE FIELD
Regulating stem cell contributions to vascularization is a challenging goal, but a fundamental aspect of regenerative medicine. Human mesenchymal stem cells retain considerable potential for adult vascular repair and regeneration therapies. They are readily obtained, rapidly proliferate in culture, display a capacity to differentiate towards endothelial or vascular smooth muscle cells, and play an important role in postnatal neovascularization in various tissue contexts. To therapeutically enhance neovascularization during ischemic disease, or inhibit neovascularization during tumorigenesis, an essential prerequisite is to determine the mechanisms which control the recruitment and differentiation of mesenchymal stem cells towards vascular cells.
AREAS COVERED IN THIS REVIEW
In this review, we describe the current understanding of how PDGF receptors contribute prominently to neovascularization, and play a decisive role in modulating mesenchymal stem cell recruitment and differentiation towards vascular cells. We discuss PDGF receptor-based therapeutic strategies to exploit mesenchymal stem cells during vascular repair and regeneration, and to control pathological neovascularization.
TAKE HOME MESSAGE
PDGF receptor signaling is emerging as a critical regulatory mechanism and important therapeutic target, that critically directs the fate of mesenchymal stem cells during postnatal neovascularization.
Topics: Animals; Humans; Mesenchymal Stem Cells; Neovascularization, Physiologic; Receptors, Platelet-Derived Growth Factor
PubMed: 20078229
DOI: 10.1517/14712590903379510 -
Tissue Engineering. Part B, Reviews Mar 2009Ever since synovium-derived mesenchymal stem cells (SMSCs) were first identified and successfully isolated in 2001, as a brand new member in MSC families, they have been... (Review)
Review
Ever since synovium-derived mesenchymal stem cells (SMSCs) were first identified and successfully isolated in 2001, as a brand new member in MSC families, they have been increasingly regarded as a promising therapeutic cell species for musculoskeletal regeneration, particularly for reconstructions of cartilage, bones, tendons, and muscles. Besides the general multipotency in common among the MSC community, SMSCs excel other sourced MSCs in higher ability of proliferation and superiority in chondrogenesis. This review summarizes the latest advances in SMSC-related studies covering their specific isolation methodologies, biological insights, and practical applications in musculoskeletal therapeutics of which an emphasis is cast on engineered chondrogenesis.
Topics: Animals; Bone and Bones; Cartilage; Cell Proliferation; Cells, Cultured; Humans; Immunosuppressive Agents; Mesenchymal Stem Cells; Muscle, Skeletal; Osteoarthritis; Phenotype; Synovial Membrane; Tendons; Tissue Engineering
PubMed: 19196118
DOI: 10.1089/ten.teb.2008.0586