Microscopic local stiffening in a supramolecular hydrogel network expedites stem cell mechanosensing in 3D and bone regeneration

2021 ◽  
Author(s):  
Weihao Yuan ◽  
Haixing Wang ◽  
Chao Fang ◽  
Yongkang Yang ◽  
Xingyu Xia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Bone Regeneration ◽  
Network Topology ◽  
Supramolecular Hydrogel ◽  
Hydrogel Network ◽  
A Cell ◽  
Cell Mechanosensing

A cell-adaptable hydrogel containing microscopically local stiffening structures shows a heterogeneous and hierarchical hydrogel network topology, thereby facilitating the 3D stellate spreading of stem cells and promoting the bone regeneration.

Accept or Reject: The Role of Immune Tolerance in the Development of Stem Cell Therapies and Possible Future Approaches

2020 ◽  
pp. 019262332091824
Author(s):  
Richard Haworth ◽  
Michaela Sharpe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Immune Recognition ◽  
Cell Of Origin ◽  
In Vivo Models ◽  
Cell Product ◽  
A Cell

In 2011, Goldring and colleagues published a review article describing the potential safety issues of novel stem cell-derived treatments. Immunogenicity and immunotoxicity of the administered cell product were considered risks in the light of clinical experience of transplantation. The relative immunogenicity of mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) was being addressed through in vitro and in vivo models. But the question arose as to whether the implanted cells needed to be identical to the recipient in every respect, including epigenetically, to evade immune recognition? If so, this set a high bar which may preclude use of many cells derived from iPSCs which have vestiges of a fetal phenotype and epigenetic memory of their cell of origin. However, for autologous iPSCs, the immunogenicity reduces once the surface antigen expression profile becomes close to that of the parent somatic cells. Therefore, a cell product containing incompletely differentiated cells could be more immunogenic. The properties of the administered cells, the immune privilege of the administration site, and the host immune status influence graft success or failure. In addition, the various approaches available to characterize potential immunogenicity of a cell therapy will be discussed.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

Abstract An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

scholarly journals The Potential of Different Origin Stem Cells in Modulating Oral Bone Regeneration Processes

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 29 ◽  
Author(s):  
Smaranda Dana Buduru ◽  
Diana Gulei ◽  
Alina-Andreea Zimta ◽  
Adrian Bogdan Tigu ◽  
Diana Cenariu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Bone Regeneration ◽  
Embryonic Stem ◽  
Short Review ◽  
Advantages And Disadvantages ◽  
Life Threatening ◽  
Induced Pluripotent ◽  
Stem Cell Isolation ◽  
The Right

Tissue engineering has gained much momentum since the implementation of stem cell isolation and manipulation for regenerative purposes. Despite significant technical improvements, researchers still have to decide which strategy (which type of stem cell) is the most suitable for their specific purpose. Therefore, this short review discusses the advantages and disadvantages of the three main categories of stem cells: embryonic stem cells, mesenchymal stem cells and induced pluripotent stem cells in the context of bone regeneration for dentistry-associated conditions. Importantly, when deciding upon the right strategy, the selection needs to be made in concordance with the morbidity and the life-threatening level of the condition in discussion. Therefore, even when a specific type of stem cell holds several advantages over others, their availability, invasiveness of the collection method and ethical standards become deciding parameters.

Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cell Activity ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
A Cell

An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.

scholarly journals Clinical Efficacy of Mesenchymal Stem Cells in Bone Regeneration in Oral Implantology. Systematic Review and Meta-Analysis

2021 ◽  
Vol 18 (3) ◽  
pp. 894
Author(s):  
Sonia Egido-Moreno ◽  
Joan Valls-Roca-Umbert ◽  
Juan Manuel Céspedes-Sánchez ◽  
José López-López ◽  
Eugenio Velasco-Ortega
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Bone Regeneration ◽  
Meta Analysis ◽  
Cell Group ◽  
Control Group ◽  
Publication Date ◽  
Native Bone

In bone regeneration, obtaining a vital bone as similar as possible to native bone is sought. This review aimed to evaluate the efficacy of stem cells in maxillary bone regeneration for implant rehabilitation and to review the different techniques for obtaining and processing these cells. A systematic review and meta-analysis were performed using the Pubmed/Medline (NCBI), Cochrane, Scielo, and Scopus databases, without restriction on the publication date. The following Mesh terms were used, combined by the Boolean operator “AND”: “dental implants” AND “stem cells” AND “bioengineering”. Applying inclusion and exclusion criteria, five articles were obtained and three were added after manual search. The results from the meta-analysis (18 patients) did not provide significant differences despite the percentage of bone formed in the maxillary sinus, favoring the stem cell group, and the analysis of the percentage of residual Bio-Oss® showed results favoring the control group. Stem cell regeneration usually shows positive vascular and viable bone formation. In conclusion, using mesenchymal stem cells in bone regeneration provides benefits in the quality of bone, similar or even superior to autologous bone, all this through a minimally invasive procedure.

Defining Adult Stem Cells by Function, not by Phenotype

2018 ◽  
Vol 87 (1) ◽  
pp. 1015-1027 ◽  
Author(s):  
Hans Clevers ◽  
Fiona M. Watt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Tissue Repair ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Open Approach ◽  
Physical Entity ◽  
Hematopoietic Stem ◽  
A Cell

Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. The nature of such a cell may be different under steady state conditions and during tissue repair. We discuss emerging examples including the renewal strategies of the skin, gut epithelium, liver, lung, and mammary gland in comparison with those of the hematopoietic system. While certain key housekeeping and developmental signaling pathways are shared between different stem cell systems, there may be no general, deeper principles underlying the renewal mechanisms of the various individual tissues.

1. What are stem cells?

2021 ◽  
pp. 1-18
Author(s):  
Jonathan Slack
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Structural Unit ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Body ◽  
Differentiated Cells ◽  
Mammalian Embryos ◽  
A Cell

‘What are stem cells?’ explains that a stem cell is a cell that can both reproduce itself and generate offspring of different functional cell types and begins by considering the nature of cells in general, wherein cells are understood to be the ultimate structural unit of an animal or plant body. Stem cells in the body persist long term, usually for the lifetime of the organism. Good examples of differentiated cells arising from stem cells are those of the skin, the blood, and the lining of the intestine. Embryonic stem cells are grown in culture from early mammalian embryos. The reason that stem cell research is seen as the source for new cures is largely because this technology offers a route to cell therapy.

Differentiation Hotspots on a Cell Cycle Related Continuum.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3703-3703
Author(s):  
Gerald A. Colvin ◽  
David Berz ◽  
Mark S. Dooner ◽  
Gerri J. Dooner ◽  
Kevin Johnson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
S Phase ◽  
Differentiation Potential ◽  
Steel Factor ◽  
A Cell ◽  
Inductive Signaling

Abstract Directed differentiation is defined as the ability to program a stem cell at the most primitive level while it still has its reproductive and full proliferative potential. This is in contrast to ex-vivo expansion where the stem cells are forced into specific lineage commitments, limiting the overall therapeutic utility. We have demonstrated differentiation “hotspots” on a cell cycle continuum (Exp Heme35:96, 2007). In this work we showed marked but reversible increases in differentiation potential to megakryocyte and granulocytes at different phases of a single cytokine induced cell cycle passage of highly purified quiescent murine lineagenegative rhodaminelowHoeschtlow (LRH) marrow stem cells. We have reproducibly induced directed stem cell differentiation by capitalizing on inherent changes in sensitivities to inductive cytokine signals in the context of cell cycle position. These cells, when exposed to thrombopoietin, FLT3-ligand and steel factor, synchronously pass through cell cycle. We have found that using a differentiation cytokine cocktail of G-CSF at 0.075ng/ml, GM-CSF at 0.0375ng/ml and steel factor at 50ng/ml, we were able to see enhanced megakaryopoiesis occurring 14-days after culture in those LRH stem cells that were in early to mid S-phase at time of inductive signaling. We have now shown that a megakaryocyte hotspot clusters around 32 hours; the G1/S interface, and that dramatic reversible changes in differentiation potential occur over one hour time intervals. We have confirmed this data by looking at LRH cells through cell cycle transit after initial cell division showing that a megakaryocyte hotspot occurs in two sequential cell cycles and still tied to S-phase at time of inductive signaling of the daughter cells. This hotspot has been demonstrated on a clonal basis, although the kinetics of the hotspot shifts when clonal as opposed to population studies are carried out. An important issue is whether in vitro cytokine exposure, separate from cell cycle status, determines the existence of the hotspot. To address this, we used Hoechst 33342 dye content to assist in separation of different cell cycle fractions (G0–1, early, mid and late components of S, G2/M) of lineage negative Sca-1+ stem cells, a cycling stem/progenitor cell population in which approximately 20% of the cells are in S-phase at isolation. These cells were only exposed to the differentiation cytokines and showed a megakaryocyte hotspot present in only early S-phase cells after 14-days of culture, showing that in vitro cell cycle phase determined the presence of the hotspot, separate from cytokine exposure. These data indicate that differentiation potential of marrow stem cells exists on a cell cycle related continuum and that this potential can be demonstrated on a single cell basis. This suggests a continuum model of stem cell regulation at the stem cell level as opposed to a pure hierarchical model.

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