scholarly journals Effect of Age and Diabetes on the Response of Mesenchymal Progenitor Cells to Fibrin Matrices

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
A. Stolzing ◽  
H. Colley ◽  
A. Scutt
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Wound Healing ◽  
Stem Cell ◽  
Fibrin Clot ◽  
Diabetic Rats ◽  
Cell Phenotype ◽  
Mesenchymal Progenitor Cells

Mesenchymal stem cells are showing increasing promise in applications such as tissue engineering and cell therapy. MSC are low in number in bone marrow, and thereforein vitroexpansion is often necessary.In vivo, stem cells often reside within a niche acting to protect the cells. These niches are composed of niche cells, stem cells, and extracellular matrix. When blood vessels are damaged, a fibrin clot forms as part of the wound healing response. The clot constitutes a form of stem cell niche as it appears to maintain the stem cell phenotype while supporting MSC proliferation and differentiation during healing. This is particularly appropriate as fibrin is increasingly being suggested as a scaffold meaning that fibrin-based tissue engineering may to some extent recapitulate wound healing. Here, we describe how fibrin modulates the clonogenic capacity of MSC derived from young/old human donors and normal/diabetic rats. Fibrin was prepared using different concentrations to modulate the stiffness of the substrate. MSC were expanded on these scaffolds and analysed. MSC showed an increased self-renewal on soft surfaces. Old and diabetic cells lost the ability to react to these signals and can no longer adapt to the changed environment.

MT1-MMP Plays a Critical Role in Hematopoiesis by Regulating HIF-Mediated Chemo-/Cytokine Gene Transcription within Niche Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2351-2351
Author(s):  
Chiemi Nishida ◽  
Kaori Sato-Kusubata ◽  
Yoshihiko Tashiro ◽  
Ismael Gritli ◽  
Aki Sato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transcription ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Stem Cell Differentiation ◽  
Cell Phenotype ◽  
Hematopoietic Stem

Abstract Abstract 2351 Stem cells reside in a physical niche. The organization of cellular niches has been shown to play a key role in regulating normal stem cell differentiation, stem cell maintenance and regeneration. Various stem cell niches have been shown to be hypoxic, thereby maintaining the stem cell phenotype of e.g. hematopoietic stem cells (HSCs) or cancer stem cells. The bone marrow (BM) niche is a rich reservoir of tissue-specific pluripotent HSCs. Proteases such as matrix metalloproteinases (MMPs) have been implicated in cell movement, partly due to their proteolytic function, and they have been linked to cellular processes such as cell proliferation and differentiation. The proteolytic function of Membrane-type 1 MMP (MT1-MMP/MMP-14) is essential for angiogenesis, arthritis and tumour growth. Recently, it has been reported that MT1-MMP is highly expressed in HSCs and stromal/niche cells. However the clear function of MT1-MMP in hematopoiesis is not well understood. To reveal the functional consequences of MT1-MMP deficiency for post-natal hematopoiesis in vivo, we have taken advantage of MT1-MMP−/− mice to demonstrate that MT1-MMP deficiency leads to impaired steady state hematopoiesis of all hematopoietic cell lineages. In a search for factors whose deficiency could cause this hematopoietic phenotype, we found not only reduced protein release, but also reduced transcription of the following growth factors/chemokines in MT1-MMP−/− mice: erythropoietin (Epo), stromal cell-derived factor-1 (SDF-1a/CXCL12), interleukin-7 (IL-7) and Kit ligand (KitL, also known as stem cell factor). All of these factors, except for Epo, are typical stromal cell-derived factors. To ensure that impaired gene transcription in vivo was not due to a lower number of stromal cells in vivo, we demonstrated that MT1-MMP knockdown in stromal cells in vitro also reduced transcription of the stromal cell derived factors SDF-1a/CXCL12, IL-7 and KitL. In contrast, overexpression of MT1-MMP in stromal cells enhanced gene transcription of these factors. All genes, whose transcription was altered in vitro and in vivo due to MT1-MMP deficiency, had one thing in common: their gene transcription is regulated by the hypoxia inducible factor-1 (HIF-1) pathway. Further mechanistic studies revealed that MT1-MMP activates the HIF-1 pathway via factor inhibiting HIF-1 (FIH-1) within niche cells, thereby inducing the transcription of HIF-responsive genes, which induce terminal hematopoietic differentiation. Thus, MT1-MMP in niche cells regulates postnatal hematopoiesis by modulating hematopoietic HIF-dependent niche factors that are critical for terminal differentiation and migration. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jianing Ding ◽  
Xin Wang ◽  
Bi Chen ◽  
Jieyuan Zhang ◽  
Jianguang Xu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Wound Repair ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Diabetic Rats

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

scholarly journals Pituitary Remodeling Throughout Life: Are Resident Stem Cells Involved?

2021 ◽  
Vol 11 ◽  
Author(s):  
Emma Laporte ◽  
Annelies Vennekens ◽  
Hugo Vankelecom
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pituitary Gland ◽  
Molecular Mechanisms ◽  
Pituitary Function ◽  
Cell Phenotype ◽  
Cell Populations ◽  
Cell Remodeling

The pituitary gland has the primordial ability to dynamically adapt its cell composition to changing hormonal needs of the organism throughout life. During the first weeks after birth, an impressive growth and maturation phase is occurring in the gland during which the distinct hormonal cell populations expand. During pubertal growth and development, growth hormone (GH) levels need to peak which requires an adaptive enterprise in the GH-producing somatotrope population. At aging, pituitary function wanes which is associated with organismal decay including the somatopause in which GH levels drop. In addition to these key time points of life, the pituitary’s endocrine cell landscape plastically adapts during specific (patho-)physiological conditions such as lactation (need for PRL) and stress (engagement of ACTH). Particular resilience is witnessed after physical injury in the (murine) gland, culminating in regeneration of destroyed cell populations. In many other tissues, adaptive and regenerative processes involve the local stem cells. Over the last 15 years, evidence has accumulated that the pituitary gland houses a resident stem cell compartment. Recent studies propose their involvement in at least some of the cell remodeling processes that occur in the postnatal pituitary but support is still fragmentary and not unequivocal. Many questions remain unsolved such as whether the stem cells are key players in the vivid neonatal growth phase and whether the decline in pituitary function at old age is associated with decreased stem cell fitness. Furthermore, the underlying molecular mechanisms of pituitary plasticity, in particular the stem cell-linked ones, are still largely unknown. Pituitary research heavily relies on transgenic in vivo mouse models. While having proven their value, answers to pituitary stem cell-focused questions may more diligently come from a novel powerful in vitro research model, termed organoids, which grow from pituitary stem cells and recapitulate stem cell phenotype and activation status. In this review, we describe pituitary plasticity conditions and summarize what is known on the involvement and phenotype of pituitary stem cells during these pituitary remodeling events.

scholarly journals Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Manuel Pedro Jimenez-García ◽  
Antonio Lucena-Cacace ◽  
Daniel Otero-Albiol ◽  
Amancio Carnero
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Cell Biology ◽  
Wnt Pathway ◽  
Ectopic Expression ◽  
Homeobox Genes ◽  
Cell Phenotype

Abstract Background Sarcomas are a very heterogeneous group of tumors with intrinsic developmental programs derived from the cell of origin. This implies a functional hierarchy inside tumors governed by sarcoma stem cells. Therefore, genetic and/or epigenetic changes profoundly affect the biology of sarcoma tumor stem cells. EMX genes are proposed to be transcription factors that are involved in the sarcomagenesis process, regardless of the neural or mesodermal embryological sarcoma origin. It has been shown that EMX1 or EMX2 overexpression reduces tumorigenic properties, while reducing the levels of these genes enhances these properties. Furthermore, it has been shown that EMX genes decrease the expression of stem cell regulatory genes and the stem cell phenotype. Taken together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-remodeling populations or sarcoma stem cells, acting as tumor suppressors in sarcoma. Methods Bioinformatic analysis, quantitative mRNA and protein expression analysis, cell models of sarcoma by ectopic expression of EMX genes. By cell biology methods we measured tumorigenesis and populations enriched on stem cell phenotypes, either in vitro or in vivo. Results In this work, we showed that the canonical Wnt pathway is one of the mechanisms that explains the relationships of EMX1/EMX2 and stem cell genes in sarcoma. The Wnt-EMX1/EMX2 relationship was validated in silico with sarcoma patient datasets, in vitro in primary derived sarcoma cell lines, and in vivo. EMX expression was found to negatively regulate the Wnt pathway. In addition, the constitutive activation of the Wnt pathway revers to a more aggressive phenotype with stem cell properties, and stemness gene transcription increased even in the presence of EMX1 and/or EMX2 overexpression, establishing the relationship among the Wnt pathway, stem cell genes and the EMX transcription factors. Conclusions Our data showed that Empty Spiracles Homeobox Genes EMX1 and EMX2 represses WNT signalling and activation of WNT pathway bypass EMX-dependent stemness repression and induces sarcomagenesis. These results also suggest the relevance of the Wnt/b-catenin/stemness axis as a therapeutic target in sarcoma.

scholarly journals Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Manuel Pedro Jimenez-García ◽  
Antonio Lucena-Cacace ◽  
Daniel Otero-Albiol ◽  
Amancio Carnero
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Neural Crest ◽  
Tumor Suppressors ◽  
Homeobox Genes ◽  
Neuronal Cell ◽  
Cell Gene Expression

AbstractThe EMX (Empty Spiracles Homeobox) genes EMX1 and EMX2 are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. The EMX1 and EMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed that EMX1/EMX2 act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4, SOX2, KLF4, MYC, NANOG, NES, and PROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lacking Emx genes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression and nestin expression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

2009 ◽  
Vol 21 (03) ◽  
pp. 149-155 ◽  
Author(s):  
Hsu-Wei Fang
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Growth Factors ◽  
Bone Cells ◽  
Cartilage Tissue Engineering ◽  
Bioactive Molecules ◽  
In Vivo Studies ◽  
Cartilage Tissue

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.

scholarly journals Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

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