scholarly journals Engineered Human Muscle Tissue from Skeletal Muscle Derived Stem Cells and Induced Pluripotent Stem Cell Derived Cardiac Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Jason Tchao ◽  
Jong Jin Kim ◽  
Bo Lin ◽  
Guy Salama ◽  
Cecilia W. Lo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Muscle Tissue ◽  
Connexin 43 ◽  
Stem Cell Differentiation ◽  
Cardiac Cells ◽  
Transcriptional Level ◽  
Skeletal Muscle Myosin ◽  
Induced Pluripotent

During development, cardiac and skeletal muscle share major transcription factors and sarcomere proteins which were generally regarded as specific to either cardiac or skeletal muscle but not both in terminally differentiated adult cardiac or skeletal muscle. Here, we investigated whether artificial muscle constructed from human skeletal muscle derived stem cells (MDSCs) recapitulates developmental similarities between cardiac and skeletal muscle. We constructed 3-dimensional collagen-based engineered muscle tissue (EMT) using MDSCs (MDSC-EMT) and compared the biochemical and contractile properties with EMT using induced pluripotent stem (iPS) cell-derived cardiac cells (iPS-EMT). Both MDSC-EMT and iPS-EMT expressed cardiac specific troponins, fast skeletal muscle myosin heavy chain, and connexin-43 mimicking developing cardiac or skeletal muscle. At the transcriptional level, MDSC-EMT and iPS-EMT upregulated both cardiac and skeletal muscle-specific genes and expressed Nkx2.5 and Myo-D proteins. MDSC-EMT displayed intracellular calcium ion transients and responses to isoproterenol. Contractile force measurements of MDSC-EMT demonstrated functional properties of immature cardiac and skeletal muscle in both tissues. Results suggest that the EMT from MDSCs mimics developing cardiac and skeletal muscle and can serve as a useful in vitro functioning striated muscle model for investigation of stem cell differentiation and therapeutic options of MDSCs for cardiac repair.

scholarly journals Conducting Polymer Mediated Electrical Stimulation Induces Multilineage Differentiation with Robust Neuronal Fate Determination of Human Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 658 ◽  
Author(s):  
Eva Tomaskovic-Crook ◽  
Qi Gu ◽  
Siti N Abdul Rahim ◽  
Gordon G Wallace ◽  
Jeremy M Crook
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Electrical Stimulation ◽  
Cell Differentiation ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Chemical Inducers ◽  
Neuronal Fate ◽  
Induced Pluripotent

Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) to augment biocompatibility and cell-effects. Extending our earlier work, which showed that CP-mediated electrical stimulation promotes human neural stem cell differentiation, here we report using electroactive PPy containing the anionic dopant dodecylbenzenesulfonate (DBS) to modulate the fate determination of human induced pluripotent stem cells (iPSCs). Remarkably, the stimulation without conventional chemical inducers resulted in the iPSCs differentiating to cells of the three germ lineages—endoderm, ectoderm, and mesoderm. The unstimulated iPSC controls remained undifferentiated. Phenotypic characterisation further showed a robust induction to neuronal fate with electrical stimulation, again without customary chemical inducers. Our findings add to the growing body of evidence supporting the use of electrical stimulation to augment stem cell differentiation, more specifically, pluripotent stem cell differentiation, and especially neuronal induction. Moreover, we have shown the versatility of electroactive PPy as a cell-compatible platform for advanced stem cell research and translation, including identifying novel mechanisms of fate regulation, tissue development, electroceuticals, and regenerative medicine.

scholarly journals Histone Deacetylase Inhibitors in Cell Pluripotency, Differentiation, and Reprogramming

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Androniki Kretsovali ◽  
Christiana Hadjimichael ◽  
Nikolaos Charmpilas
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Stem Cell Differentiation ◽  
Induced Pluripotent

Histone deacetylase inhibitors (HDACi) are small molecules that have important and pleiotropic effects on cell homeostasis. Under distinct developmental conditions, they can promote either self-renewal or differentiation of embryonic stem cells. In addition, they can promote directed differentiation of embryonic and tissue-specific stem cells along the neuronal, cardiomyocytic, and hepatic lineages. They have been used to facilitate embryo development following somatic cell nuclear transfer and induced pluripotent stem cell derivation by ectopic expression of pluripotency factors. In the latter method, these molecules not only increase effectiveness, but can also render the induction independent of the oncogenes c-Myc and Klf4. Here we review the molecular pathways that are involved in the functions of HDAC inhibitors on stem cell differentiation and reprogramming of somatic cells into pluripotency. Deciphering the mechanisms of HDAC inhibitor actions is very important to enable their exploitation for efficient and simple tissue regeneration therapies.

scholarly journals Enhanced Osteogenic Differentiation of Pluripotent Stem Cells via γ-Secretase Inhibition

2021 ◽  
Vol 22 (10) ◽  
pp. 5215
Author(s):  
Summer Helmi ◽  
Leili Rohani ◽  
Ahmed Zaher ◽  
Youssry El Hawary ◽  
Derrick Rancourt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Notch Signaling ◽  
Induced Pluripotent Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Healing ◽  
Pluripotent Stem Cells ◽  
Healing Process ◽  
Stem Cell Differentiation ◽  
Induced Pluripotent

Bone healing is a complex, well-organized process. Multiple factors regulate this process, including growth factors, hormones, cytokines, mechanical stimulation, and aging. One of the most important signaling pathways that affect bone healing is the Notch signaling pathway. It has a significant role in controlling the differentiation of bone mesenchymal stem cells and forming new bone. Interventions to enhance the healing of critical-sized bone defects are of great importance, and stem cell transplantations are eminent candidates for treating such defects. Understanding how Notch signaling impacts pluripotent stem cell differentiation can significantly enhance osteogenesis and improve the overall healing process upon transplantation. In Rancourt’s lab, mouse embryonic stem cells (ESC) have been successfully differentiated to the osteogenic cell lineage. This study investigates the role of Notch signaling inhibition in the osteogenic differentiation of mouse embryonic and induced pluripotent stem cells (iPS). Our data showed that Notch inhibition greatly enhanced the differentiation of both mouse embryonic and induced pluripotent stem cells.

scholarly journals Using single-cell entropy to describe the dynamics of reprogramming and differentiation of induced pluripotent stem cells

2020 ◽  
Vol 34 (30) ◽  
pp. 2050288
Author(s):  
Y. Ye ◽  
Z. Yang ◽  
M. Zhu ◽  
J. Lei
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Cell Level ◽  
Macroscopic Variable ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) provide a great model to study the process of stem cell reprogramming and differentiation. Single-cell RNA sequencing (scRNA-seq) enables us to investigate the reprogramming process at single-cell level. Here, we introduce single-cell entropy (scEntropy) as a macroscopic variable to quantify the cellular transcriptome from scRNA-seq data during reprogramming and differentiation of iPSCs. scEntropy measures the relative order parameter of genomic transcriptions at single cell level during the process of cell fate changes, which show increase tendency during differentiation, and decrease upon reprogramming. Hence, scEntropy provides an intrinsic measurement of the cell state, and can be served as a pseudo-time of the stem cell differentiation process. Moreover, based on the evolutionary dynamics of scEntropy, we construct a phenomenological Fokker-Planck equation model and the corresponding stochastic differential equation for the process of cell state transitions during pluripotent stem cell differentiation. These equations provide further insights to infer the processes of cell fates changes and stem cell differentiation. This study is the first to introduce the novel concept of scEntropy to quantify the biological process of iPSC, and suggests that the scEntropy can provide a suitable macroscopic variable for single cells to describe cell fate transition during differentiation and reprogramming of stem cells.

scholarly journals Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells

2012 ◽  
Vol 21 (15) ◽  
pp. 2798-2808 ◽  
Author(s):  
Xiaohu Ge ◽  
I-Ning E. Wang ◽  
Ildiko Toma ◽  
Vittorio Sebastiano ◽  
Jianwei Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Cells ◽  
Induced Pluripotent

scholarly journals Stem Cells: The Game Changers of Human Cardiac Disease Modelling and Regenerative Medicine

2019 ◽  
Vol 20 (22) ◽  
pp. 5760 ◽  
Author(s):  
Elvira Immacolata Parrotta ◽  
Stefania Scalise ◽  
Luana Scaramuzzino ◽  
Giovanni Cuda
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Human Disease ◽  
Cell Biology ◽  
Stem Cell Differentiation ◽  
Patient Specific ◽  
To Come ◽  
Induced Pluripotent ◽  
Based Medicine

A comprehensive understanding of the molecular basis and mechanisms underlying cardiac diseases is mandatory for the development of new and effective therapeutic strategies. The lack of appropriate in vitro cell models that faithfully mirror the human disease phenotypes has hampered the understanding of molecular insights responsible of heart injury and disease development. Over the past decade, important scientific advances have revolutionized the field of stem cell biology through the remarkable discovery of reprogramming somatic cells into induced pluripotent stem cells (iPSCs). These advances allowed to achieve the long-standing ambition of modelling human disease in a dish and, more interestingly, paved the way for unprecedented opportunities to translate bench discoveries into new therapies and to come closer to a real and effective stem cell-based medicine. The possibility to generate patient-specific iPSCs, together with the new advances in stem cell differentiation procedures and the availability of novel gene editing approaches and tissue engineering, has proven to be a powerful combination for the generation of phenotypically complex, pluripotent stem cell-based cellular disease models with potential use for early diagnosis, drug screening, and personalized therapy. This review will focus on recent progress and future outcome of iPSCs technology toward a customized medicine and new therapeutic options.

scholarly journals Using single-cell entropy to describe the dynamics of reprogramming and differentiation of induced pluripotent stem cells

2020 ◽  
Author(s):  
Yusong Ye ◽  
Zhuoqin Yang ◽  
Meixia Zhu ◽  
Jinzhi Lei
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Single Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Cell Level ◽  
Macroscopic Variable ◽  
Induced Pluripotent

AbstractInduced pluripotent stem cells (iPSCs) provide a great model to study the process of stem cell reprogramming and differentiation. Single-cell RNA sequencing (scRNA-seq) enables us to investigate the reprogramming process at single-cell level. Here, we introduce single-cell entropy (scEntropy) as a macroscopic variable to quantify the cellular transcriptome from scRNA-seq data during reprogramming and differentiation of iPSCs. scEntropy measures the relative order parameter of genomic transcriptions at single cell level during the process of cell fate changes, which show increase tendency during differentiation, and decrease upon reprogramming. Hence, scEntropy provides an intrinsic measurement of the cell state, and can be served as a pseudo-time of the stem cell differentiation process. Moreover, based on the evolutionary dynamics of scEntropy, we construct a phenomenological Fokker-Planck equation model and the corresponding stochastic differential equation for the process of cell state transitions during pluripotent stem cell differentiation. These equations provide further insights to infer the processes of cell fates changes and stem cell differentiation. This study is the first to introduce the novel concept of scEntropy to quantify the biological process of iPSC, and suggests that the scEntropy can provide a suitable macroscopic variable for single cells to describe cell fate transition during differentiation and reprogramming of stem cells.

scholarly journals HIF-1α Affects the Neural Stem Cell Differentiation of Human Induced Pluripotent Stem Cells via MFN2-Mediated Wnt/β-Catenin Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Peng Cui ◽  
Ping Zhang ◽  
Lin Yuan ◽  
Li Wang ◽  
Xin Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Neural Stem Cell ◽  
Pluripotent Stem Cells ◽  
Stem Cell Differentiation ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Induced Pluripotent

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.

scholarly journals Current understanding and future perspectives of the roles of sirtuins in the reprogramming and differentiation of pluripotent stem cells

2018 ◽  
Vol 243 (6) ◽  
pp. 563-575 ◽  
Author(s):  
Yi-Chao Hsu ◽  
Yu-Ting Wu ◽  
Chia-Ling Tsai ◽  
Yau-Huei Wei
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Stem Cell Differentiation ◽  
Ppar Gamma ◽  
Metabolic Reprogramming ◽  
Induced Pluripotent

In mammalian cells, there are seven members of the sirtuin protein family (SIRT1–7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a–SIRT1–p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells. SIRT4 has no direct role in regulating reprogramming but may have the potential to prevent senescence of somatic cells and to facilitate the reprogramming of iPSCs. SIRT5 can deacetylate STAT3, which is an important transcription factor in regulating pluripotency and differentiation of stem cells. SIRT6 can enhance the reprogramming efficiency of iPSCs from aged skin fibroblasts through miR-766 and increase the expression levels of the reprogramming genes including Sox2, Oct4, and Nanog through acetylation of histone H3 lysine 56. SIRT7 plays a regulatory role in the process of mesenchymal-to-epithelial transition (MET), which has been suggested to be a crucial process in the generation of iPSCs from fibroblasts. In this review, we summarize recent findings of the roles of sirtuins in the metabolic reprogramming and differentiation of stem cells and discuss the bidirectional changes in the gene expression and activities of sirtuins in the commitment of differentiation of mesenchymal stem cells (MSCs) and reprogramming of somatic cells to iPSCs, respectively. Thus, understanding the molecular basis of the interplay between different sirtuins and mitochondrial function will provide new insights into the regulation of differentiation of stem cells and iPSCs formation, respectively, and may help design effective stem cell therapies for regenerative medicine. Impact statement This is an extensive review of the recent advances in our understanding of the roles of some members of the sirtuins family, such as SIRT1, SIRT2, SIRT3, and SIRT6, in the regulation of intermediary metabolism during stem cell differentiation and in the reprogramming of somatic cells to form induced pluripotent stem cells (iPSCs). This article provides an updated integrated view on the mechanisms by which sirtuins-mediated posttranslational protein modifications regulate mitochondrial biogenesis, bioenergetics, and antioxidant defense in the maintenance and differentiation of stem cells and in iPSCs formation, respectively.

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