scholarly journals Non-Ionizing Radiation for Cardiac Human Amniotic Mesenchymal Stromal Cell Commitment: A Physical Strategy in Regenerative Medicine

2018 ◽  
Vol 19 (8) ◽  
pp. 2324 ◽  
Author(s):  
Mario Ledda ◽  
Enrico D’Emilia ◽  
Maria Lolli ◽  
Rodolfo Marchese ◽  
Claudio De Lazzari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Myocardial Damage ◽  
Stem Cell Differentiation ◽  
Differentiation Markers ◽  
Innovative Strategy ◽  
Cell Commitment

Cell therapy is an innovative strategy for tissue repair, since adult stem cells could have limited regenerative ability as in the case of myocardial damage. This leads to a local contractile dysfunction due to scar formation. For these reasons, refining strategy approaches for “in vitro” stem cell commitment, preparatory to the “in vivo” stem cell differentiation, is imperative. In this work, we isolated and characterized at molecular and cellular level, human Amniotic Mesenchymal Stromal Cells (hAMSCs) and exposed them to a physical Extremely Low Frequency Electromagnetic Field (ELF-EMF) stimulus and to a chemical Nitric Oxide treatment. Physically exposed cells showed a decrease of cell proliferation and no change in metabolic activity, cell vitality and apoptotic rate. An increase in the mRNA expression of cardiac and angiogenic differentiation markers, confirmed at the translational level, was also highlighted in exposed cells. Our data, for the first time, provide evidence that physical ELF-EMF stimulus (7 Hz, 2.5 µT), similarly to the chemical treatment, is able to trigger hAMSC cardiac commitment. More importantly, we also observed that only the physical stimulus is able to induce both types of commitments contemporarily (cardiac and angiogenic), suggesting its potential use to obtain a better regenerative response in cell-therapy protocols.

scholarly journals Human adipose stem cell differentiation is highly affected by cancer cells both in vitro and in vivo: implication for autologous fat grafting

2017 ◽  
Vol 8 (1) ◽  
pp. e2568-e2568 ◽  
Author(s):  
Francesca Paino ◽  
Marcella La Noce ◽  
Diego Di Nucci ◽  
Giovanni Francesco Nicoletti ◽  
Rosa Salzillo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Fat Grafting ◽  
Adipose Stem Cell ◽  
Autologous Fat Grafting ◽  
Autologous Fat ◽  
Human Adipose Stem Cell

scholarly journals Diabetic Retinopathy and Stem Cell Therapy

2021 ◽  
Author(s):  
Sevil Kestane
Keyword(s):  
Stem Cells ◽  
Diabetic Retinopathy ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Treatment Strategies ◽  
Cell Therapies ◽  
Long Time

This overview was evaluated by the development of diabetic retinopathy (DR) and the stem cell therapy approach. DR is a microvascular complication of diabetes mellitus, characterized by damage to the retinal blood vessels leading to progressive loss of vision. However, the pathophysiological mechanisms are complicated and not completely understood yet. The current treatment strategies have included medical, laser, intravitreal, and surgical approaches. It is known that the use of mesenchymal stem cells (MSC), which has a great potential, is promising for the treatment of many degenerative disorders, including the eye. In retinal degenerative diseases, MSCs were ameliorated retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Stem cell therapies show promise in neurodegenerative diseases. However, it is very important to know which type of stem cell will be used in which situations, the amount of stem cells to be applied, the method of application, and its physiological/neurophysiological effects. Therefore, it is of great importance to evaluate this subject physiologically. After stem cell application, its safety and efficacy should be followed for a long time. In the near future, widespread application of regenerative stem cell therapy may be a standard treatment in DR.

scholarly journals Fetal liver mesenchymal stem cells restore ovarian function in premature ovarian insufficiency by targeting MT1

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Boxian Huang ◽  
Chunfeng Qian ◽  
Chenyue Ding ◽  
Qingxia Meng ◽  
Qinyan Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Ovarian Function ◽  
Ovarian Insufficiency ◽  
Apoptotic Genes

Abstract Background With the development of regenerative medicine and tissue engineering technology, almost all stem cell therapy is efficacious for the treatment of premature ovarian failure (POF) or premature ovarian insufficiency (POI) animal models, whereas little stem cell therapy has been practiced in clinical settings. The underlying molecular mechanism and safety of stem cell treatment in POI are not fully understood. In this study, we explored whether fetal mesenchymal stem cells (fMSCs) from the liver restore ovarian function and whether melatonin membrane receptor 1 (MT1) acts as a regulator for treating POI disease. Methods We designed an in vivo model (chemotherapy-induced ovary damage) and an in vitro model (human ovarian granulosa cells (hGCs)) to understand the efficacy and molecular cues of fMSC treatment of POI. Follicle development was observed by H&E staining. The concentration of sex hormones in serum (E2, AMH, and FSH) and the concentration of oxidative and antioxidative metabolites and the enzymes MDA, SOD, CAT, LDH, GR, and GPx were measured by ELISA. Flow cytometry (FACS) was employed to detect the percentages of ROS and proliferation rates. mRNA and protein expression of antiapoptotic genes (SURVIVIN and BCL2), apoptotic genes (CASPASE-3 and CASPASE-9), and MT1 and its downstream genes (JNK1, PCNA, AMPK) were tested by qPCR and western blotting. MT1 siRNA and related antagonists were used to assess the mechanism. Results fMSC treatment prevented cyclophosphamide (CTX)-induced follicle loss and recovered sex hormone levels. Additionally, fMSCs significantly decreased oxidative damage, increased oxidative protection, improved antiapoptotic effects, and inhibited apoptotic genes in vivo and in vitro. Furthermore, fMSCs also upregulated MT1, JNK1, PCNA, and AMPK at the mRNA and protein levels. With MT1 knockdown or antagonist treatment in normal hGCs, the protein expression of JNK1, PCNA, and AMPK and the percentage of proliferation were impaired. Conclusions fMSCs might play a crucial role in mediating follicular development in the POI mouse model and stimulating the activity of POI hGCs by targeting MT1.

scholarly journals MHC class II cell-autonomously regulates self-renewal and differentiation of normal and malignant B cells

Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1108-1118 ◽  
Author(s):  
Julia Merkenschlager ◽  
Urszula Eksmond ◽  
Luca Danelli ◽  
Jan Attig ◽  
George R. Young ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cells ◽  
B Cell ◽  
Stem Cell Differentiation ◽  
Class Ii ◽  
Cell Phenotype ◽  
Self Renewal ◽  
Mhc Ii

Abstract Best known for presenting antigenic peptides to CD4+ T cells, major histocompatibility complex class II (MHC II) also transmits or may modify intracellular signals. Here, we show that MHC II cell-autonomously regulates the balance between self-renewal and differentiation in B-cell precursors, as well as in malignant B cells. Initiation of MHC II expression early during bone marrow B-cell development limited the occupancy of cycling compartments by promoting differentiation, thus regulating the numerical output of B cells. MHC II deficiency preserved stem cell characteristics in developing pro-B cells in vivo, and ectopic MHC II expression accelerated hematopoietic stem cell differentiation in vitro. Moreover, MHC II expression restrained growth of murine B-cell leukemia cell lines in vitro and in vivo, independently of CD4+ T-cell surveillance. Our results highlight an important cell-intrinsic contribution of MHC II expression to establishing the differentiated B-cell phenotype.

Abstract 213: Evolving Challenges in Promoting Stem Cell Based Cardiovascular Repair and Regeneration

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Mani T Valarmathi ◽  
Jiang Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Muscle ◽  
Adult Stem Cells ◽  
Cardiac Tissue ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Myocardial Damage ◽  
Culture Conditions

Introduction: Use of adult stem cells in the stimulation of mammalian cardiac muscle regeneration is in its infancy, and to date, it has been difficult to determine the efficacy of the procedures that have been employed. The outstanding question remains whether stem cells derived from the bone-marrow or some other location within or outside of the heart can populate a region of myocardial damage and transform into tissue-specific cells, and also exhibit functional synchronization. As a result, this necessitates the development of an appropriate in vitro three-dimensional (3-D) model of cardiomyogenesis and prompts the development of a 3-D cardiac muscle construct for tissue engineering purposes, especially using the adult stem cells. Hypothesis: Functioning vascularized cardiac tissue can be generated by the interaction of human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human multipotent mesenchymal stem cells (hMSCs) on a 3-D prevascularized collagen cell carrier (CCC) scaffold. Methods and Results: In order to achieve the above aim, we have developed an in vitro 3-D functioning vascularized cardiac muscle construct using hiPSC-ECMs and hMSCs. First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured on 3-D CCCs for 7 days under vasculogenic culture conditions, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of micro vessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed dramatic neo-angiogenesis and neo-cardiomyogenesis. Conclusions: Thus, our unique 3-D co-culture system provided us the apt in vitro functioning prevascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

Abstract 78: Pnmt+ "Primer" Cells Give Rise to Cardiac Myocytes and Neurons in the Mammalian Heart: Development of New Experimental Tools for Cardiac Regenerative Medicine Applications

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Namita M Varudkar ◽  
Jixiang Xia ◽  
Ibrahim Abukenda ◽  
Karl Pfeifer ◽  
Steven Ebert
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Neural Crest ◽  
Heart Development ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Stem Cell Differentiation ◽  
Left Ventricular

Phenylethanolamine n-methyltransferase (Pnmt) catalyzes the conversion of norepinephrine to epinephrine, and thus serves as a marker for adrenergic cells. We employed a combination of immunofluorescent histochemical staining and genetic fate-mapping strategies to show that two separate Pnmt+ cell populations contribute to heart development. Intrinsic cardiac adrenergic (ICA) cells originate from the primary heart field, and contribute to pacemaking, conduction, and working (contractile) myocardium. A second population of cardiac Pnmt+ cells is derived from migrating neural crest. These neural crest adrenergic (NCA) cells appear to contribute to cardiac neurons. By adulthood, most of the Pnmt+ cells show a distinctively left-sided orientation in the heart, with nearly 90% of them being found in the left atrium and ventricle. Surprisingly large swaths of ventricular muscle are derived from Pnmt+ primer cells. Since this region of the heart is highly vulnerable to coronary artery disease and often sustains varying degrees of damage following myocardial infarction, we hypothesize that directed stem cell differentiation into Pnmt+ primer cells could serve as a valuable resource for repair and/or regeneration of left ventricular myocardium for heart disease patients. To test this hypothesis, we have generated stable recombinant mouse embryonic stem cell (mESC) lines that express various fluorescent marker proteins under the control of the endogenous Pnmt gene regulatory network. These cells can be rapidly expanded in culture, sorted, and used for transplantation studies in animal models to determine their therapeutic effectiveness. The cells can be induced along cardiogenic or neurogenic pathways in vitro, and the resulting Pnmt+ cells from each population can then be collected and tested in vivo. To achieve this goal, we have knocked-in a nuclear-localized enhanced green fluorescent protein into the Pnmt locus to create Pnmt-nEGFP recombinant mESCs and mice. We show that nEGFP expression is specifically expressed in Pnmt+ cells in vitro and in vivo. This strategy allows us to identify and isolate Pnmt+ cells to evaluate their effectiveness for cardiac regenerative medicine applications. .

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.

Sign in / Sign up

Export Citation Format

Share Document