scholarly journals Multi-differentiation potential is necessary for optimal tenogenesis of tendon stem cells

2019 ◽  
Author(s):  
Ibtesam Rajpar ◽  
Jennifer G. Barrett
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Cell Phenotype ◽  
Differentiation Potential ◽  
Therapeutic Benefits ◽  
Tendon Stem Cells ◽  
Stem Cell Lines ◽  
Population Doublings ◽  
Cell Phenotypes

ABSTRACTBackgroundTendon injury is a significant clinical problem, and regenerative treatments are limited by our understanding of endogenous tendon stem cells. Recent evidence suggests that tendon stem cells are diverse in phenotypic character, and may in fact exist on a spectrum of differentiation capacities. However, the functional significance of each differentiation phenotype is poorly understood. Toward this end, we performed a comprehensive assessment of differentiation capacity toward four connective tissue lineages (adipose, bone, cartilage and tendon) with clonal tendon stem cell lines to: 1) evaluate the differences, if any, in tenogenic potential, and 2) identify the relationships in differentiation phenotype and proliferation capacity.MethodsTendon stem cells were derived from whole equine flexor tendons for this study (N=3). Clonal tendon stem lines were generated by low-density cell plating, and subjected to standard assays of tri-lineage differentiation and population doublings. For tenogenesis, a previously engineered three-dimensional hydrogel construct was incorporated. Differentiation was quantified by the relative gene expression of lineage-specific markers, and confirmed with lineage-specific cell staining. Tenogenesis was further analyzed by hydrogel contraction and histomorphometry. Statistical significance was determined using analysis of variance and post-hoc Tukey’s tests.ResultsThree distinct tendon stem cell phenotypes were identified, namely differentiation toward: 1) adipose, bone, cartilage and tendon, 2) bone, cartilage and tendon, or 3) adipose, cartilage and tendon. Further, a positive correlation was found in the ability to differentiate toward all four lineages and the generation of a robust, composite tendon-like construct upon tenogenesis, manifested by the strongest expressions of scleraxis and mohawk, and parallel alignment of tenocyte-like cells with elongated cell morphologies. Significantly increased numbers of cumulative cell population doublings were seen in the absence of adipogenic potential in clonal tendon stem cell lines.ConclusionsOur study strengthens reports on the heterogeneous character of tendon stem cells and identifies key differences in their differentiation and proliferative potentials. Isolation of potent tendon stem cell populations from tendon stromal fractions may yield improved therapeutic benefits in clinical models of repair and promote a native, regenerative phenotype in engineered tendons. Future studies may be targeted to understanding the functional contributions of each tendon stem cell phenotype in vivo, and identifying additional cell phenotypes.

Ex Uno Plures: Molecular Designs for Embryonic Pluripotency

2015 ◽  
Vol 95 (1) ◽  
pp. 245-295 ◽  
Author(s):  
Kyle M. Loh ◽  
Bing Lim ◽  
Lay Teng Ang
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Cell Lines ◽  
Multilineage Differentiation ◽  
Pluripotent Cells ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Pluripotency Factors ◽  
Stem Cell Lines

Pluripotent cells in embryos are situated near the apex of the hierarchy of developmental potential. They are capable of generating all cell types of the mammalian body proper. Therefore, they are the exemplar of stem cells. In vivo, pluripotent cells exist transiently and become expended within a few days of their establishment. Yet, when explanted into artificial culture conditions, they can be indefinitely propagated in vitro as pluripotent stem cell lines. A host of transcription factors and regulatory genes are now known to underpin the pluripotent state. Nonetheless, how pluripotent cells are equipped with their vast multilineage differentiation potential remains elusive. Consensus holds that pluripotency transcription factors prevent differentiation by inhibiting the expression of differentiation genes. However, this does not explain the developmental potential of pluripotent cells. We have presented another emergent perspective, namely, that pluripotency factors function as lineage specifiers that enable pluripotent cells to differentiate into specific lineages, therefore endowing pluripotent cells with their multilineage potential. Here we provide a comprehensive overview of the developmental biology, transcription factors, and extrinsic signaling associated with pluripotent cells, and their accompanying subtypes, in vitro heterogeneity and chromatin states. Although much has been learned since the appreciation of mammalian pluripotency in the 1950s and the derivation of embryonic stem cell lines in 1981, we will specifically emphasize what currently remains unclear. However, the view that pluripotency factors capacitate differentiation, recently corroborated by experimental evidence, might perhaps address the long-standing question of how pluripotent cells are endowed with their multilineage differentiation potential.

scholarly journals Fetal hemoglobin in paroxysmal nocturnal hemoglobinuria (PNH): evidence for derivation of HbF-containing erythrocytes (F cells) from the PNH clone as well as from normal hemopoietic stem cell lines

Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 740-749 ◽  
Author(s):  
T Papayannopoulou ◽  
W Rosse ◽  
G Stamatoyannopoulos
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Whole Blood ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Red Cells ◽  
Hemopoietic Stem Cell ◽  
Normal Cells ◽  
F Cells ◽  
Stem Cell Lines

Abstract The cellular distribution of HbF was studied in nine patients with paroxysmal nocturnal hemoglobinuria (PNH) by measuring the level of HbF and determining the number of HbF-containing red cells (F cells) in whole blood and in the population of normal cells obtained after immune lysis of the abnormal erythrocytes. The amounts of HbF and the F cell frequencies found in the normal red cells were strikingly similar to the values seen in whole blood. The observed frequencies of F cells in normal cells best fitted those expected under the assumption that the F cells arise equally from normal hemopoietic stem cells and from the stem cells with the PNH defect. Since PNH appears to be a clonal hemopoietic stem cell disorder, this evidence argues against a derivation of F cells from distinct pluripotent stem cell lines.

scholarly journals PPARγ2 Regulates a Molecular Signature of Marrow Mesenchymal Stem Cells

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-13 ◽  
Author(s):  
K. R. Shockley ◽  
C. J. Rosen ◽  
G. A. Churchill ◽  
B. Lecka-Czernik
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Molecular Signature ◽  
Cell Phenotype ◽  
Differentiation Potential ◽  
Gene Markers ◽  
Therapeutic Consequences ◽  
Expression Of Genes ◽  
Stem Cell Phenotype

Bone formation and hematopoiesis are anatomically juxtaposed and share common regulatory mechanisms. Bone marrow mesenchymal stromal/stem cells (MSC) contain a compartment that provides progeny with bone forming osteoblasts and fat laden adipocytes as well as fibroblasts, chondrocytes, and muscle cells. In addition, marrow MSC provide an environment for support of hematopoiesis, including the development of bone resorbing osteoclasts. The PPARγ2 nuclear receptor is an adipocyte-specific transcription factor that controls marrow MSC lineage allocation toward adipocytes and osteoblasts. Increased expression of PPARγ2 with aging correlates with changes in the MSC status in respect to both their intrinsic differentiation potential and production of signaling molecules that contribute to the formation of a specific marrow microenvironment. Here, we investigated the effect of PPARγ2 on MSC molecular signature in respect to the expression of gene markers associated exclusively with stem cell phenotype, as well as genes involved in the formation of a stem cell supporting marrow environment. We found that PPARγ2 is a powerful modulator of stem cell-related gene expression. In general, PPARγ2 affects the expression of genes specific for the maintenance of stem cell phenotype, including LIF, LIF receptor, Kit ligand, SDF-1, Rex-1/Zfp42, and Oct-4. Moreover, the antidiabetic PPARγagonist TZD rosiglitazone specifically affects the expression of “stemness” genes, including ABCG2, Egfr, and CD44. Our data indicate that aging and antidiabetic TZD therapy may affect mesenchymal stem cell phenotype through modulation of PPARγ2 activity. These observations may have important therapeutic consequences and indicate a need for more detailed studies of PPARγ2 role in stem cell biology.

scholarly journals Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells

2015 ◽  
Vol 370 (1680) ◽  
pp. 20140365 ◽  
Author(s):  
Maria Rostovskaya ◽  
Nicholas Bredenkamp ◽  
Austin Smith
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cells ◽  
Type I ◽  
Pancreatic Progenitors ◽  
Stem Cell Lines

Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification.

Epigenetic regulation in stem cell development, cell fate conversion, and reprogramming

2015 ◽  
Vol 6 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Kazuyuki Ohbo ◽  
Shin-ichi Tomizawa
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cell Fate ◽  
Cell Lines ◽  
Cell Fate Decisions ◽  
Micro Rnas ◽  
Stem Cell Lines ◽  
Cell Fate Conversion

AbstractStem cells are identified classically by an in vivo transplantation assay plus additional characterization, such as marker analysis, linage-tracing and in vitro/ex vivo differentiation assays. Stem cell lines have been derived, in vitro, from adult tissues, the inner cell mass (ICM), epiblast, and male germ stem cells, providing intriguing insight into stem cell biology, plasticity, heterogeneity, metastable state, and the pivotal point at which stem cells irreversibly differentiate to non-stem cells. During the past decade, strategies for manipulating cell fate have revolutionized our understanding about the basic concept of cell differentiation: stem cell lines can be established by introducing transcription factors, as with the case for iPSCs, revealing some of the molecular interplay of key factors during the course of phenotypic changes. In addition to de-differentiation approaches for establishing stem cells, another method has been developed whereby induced expression of certain transcription factors and/or micro RNAs artificially converts differentiated cells from one committed lineage to another; notably, these cells need not transit through a stem/progenitor state. The molecular cues guiding such cell fate conversion and reprogramming remain largely unknown. As differentiation and de-differentiation are directly linked to epigenetic changes, we overview cell fate decisions, and associated gene and epigenetic regulations.

Male germ line stem cells: from cell biology to cell therapy

2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Germ Cells ◽  
Germ Line ◽  
Current Status ◽  
Seminiferous Tubules ◽  
Male Germ Line ◽  
Male Germ Cells ◽  
Stem Cell Lines

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.

scholarly journals Generation of human pluripotent stem cell lines (iPSCs) from mesenchymal stem cells (MSCs) from three elderly patients with osteoarthritis

2020 ◽  
Vol 44 ◽  
pp. 101721 ◽  
Author(s):  
Lydiane Pichard ◽  
Jean-Marc Brondelo ◽  
Fabienne Becker ◽  
Romain Desprat ◽  
Frédéric De Ceuninck ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Elderly Patients ◽  
Cell Lines ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Stem Cell Lines

scholarly journals Embryos, Clones, and Stem Cells: A Scientific Primer

2004 ◽  
Vol 4 ◽  
pp. 662-715 ◽  
Author(s):  
Kenyon S. Tweedell
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Cell Lines ◽  
Human Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Normal Function ◽  
Cell Recovery ◽  
Stem Cell Lines

This article is intended to give the nonspecialist an insight into the nuances of “clones”, cloning, and stem cells. It distinguishes embryonic and adult stem cells, their normal function in the organism, their origin, and how they are recovered to produce stem cell lines in culture. As background, the fundamental processes of embryo development are reviewed and defined, since the manipulation of stem cell lines into desired specialized cells employs many of the same events. Stem cells are defined and characterized and shown how they function in the intact organism during early development and later during cell regeneration in the adult. The complexity of stem cell recovery and their manipulation into specific cells and tissue is illustrated by reviewing current experimentation on both embryonic and adult stem cells in animals and limited research on human stem cell lines. The current and projected use of stem cells for human diseases and repair, along with the expanding methodology for the recovery of human embryonic stem cells, is described. An assessment on the use of human embryonic stem cells is considered from ethical, legal, religious, and political viewpoints.

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