scholarly journals Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Jason P. Weick
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Functional Properties ◽  
New Technologies ◽  
Synaptic Activity ◽  
Model Systems ◽  
Phenotypic Characterization ◽  
Human Stem Cell ◽  
Human Stem Cells

Stem cell-derived neurons from various source materials present unique model systems to examine the fundamental properties of central nervous system (CNS) development as well as the molecular underpinnings of disease phenotypes. In order to more accurately assess potential therapies for neurological disorders, multiple strategies have been employed in recent years to produce neuronal populations that accurately representin vivoregional and transmitter phenotypes. These include new technologies such as direct conversion of somatic cell types into neurons and glia which may accelerate maturation and retain genetic hallmarks of aging. In addition, novel forms of genetic manipulations have brought human stem cells nearly on par with those of rodent with respect to gene targeting. For neurons of the CNS, the ultimate phenotypic characterization lies with their ability to recapitulate functional properties such as passive and active membrane characteristics, synaptic activity, and plasticity. These features critically depend on the coordinated expression and localization of hundreds of ion channels and receptors, as well as scaffolding and signaling molecules. In this review I will highlight the current state of knowledge regarding functional properties of human stem cell-derived neurons, with a primary focus on pluripotent stem cells. While significant advances have been made, critical hurdles must be overcome in order for this technology to support progression toward clinical applications.

The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1433-1442 ◽  
Author(s):  
Clinton J. V. Campbell ◽  
Jung Bok Lee ◽  
Marilyne Levadoux-Martin ◽  
Tracy Wynder ◽  
Anargyros Xenocostas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Functional Dependence ◽  
Family Members ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Renewal Function ◽  
Self Renewal ◽  
Stem Cell Hierarchy

The molecular basis for the unique proliferative and self-renewal properties that hierarchically distinguish human stem cells from progenitors and terminally differentiated cells remains largely unknown. We report a role for the Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) as an indispensable regulator of self-renewal in human stem cells and show that a functional dependence on Mcl-1 defines the human stem cell hierarchy. In vivo pharmacologic targeting of the Bcl-2 family members in human hematopoietic stem cells (HSCs) and human leukemic stem cells reduced stem cell regenerative and self-renewal function. Subsequent protein expression studies showed that, among the Bcl-2 family members, only Mcl-1 was up-regulated exclusively in the human HSC fraction on in vivo regeneration of hematopoiesis. Short hairpin RNA–knockdown of Mcl-1 in human cord blood cells did not affect survival in the HSC or hematopoietic progenitor cell fractions in vitro but specifically reduced the in vivo self-renewal function of human HSCs. Moreover, knockdown of Mcl-1 in ontogenetically primitive human pluripotent stem cells resulted in almost complete ablation of stem cell self-renewal function. Our findings show that Mcl-1 is an essential regulator of stem cell self-renewal in humans and therefore represents an axis for therapeutic interventions.

scholarly journals Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Samantha N. Lanjewar ◽  
Steven A. Sloan
Keyword(s):  
Nervous System ◽  
Stem Cell ◽  
System Development ◽  
Stem Cell Differentiation ◽  
Nervous System Development ◽  
Model Systems ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Health And Disease ◽  
Species Specific

Glia are present in all organisms with a central nervous system but considerably differ in their diversity, functions, and numbers. Coordinated efforts across many model systems have contributed to our understanding of glial-glial and neuron-glial interactions during nervous system development and disease, but human glia exhibit prominent species-specific attributes. Limited access to primary samples at critical developmental timepoints constrains our ability to assess glial contributions in human tissues. This challenge has been addressed throughout the past decade via advancements in human stem cell differentiation protocols that now offer the ability to model human astrocytes, oligodendrocytes, and microglia. Here, we review the use of novel 2D cell culture protocols, 3D organoid models, and bioengineered systems derived from human stem cells to study human glial development and the role of glia in neurodevelopmental disorders.

Patentability of inventions involving human stem cells in Europe

10.5912/jcb6 ◽  
1969 ◽  
Vol 9 (1) ◽  
Author(s):  
Philippe Bouvet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
European Patent ◽  
Patent Office ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Ethical Aspects ◽  
Private Companies ◽  
European Group

In the last two years, research into stem cells has raised extraordinary therapeutic hopes – such as regenerative medicine – but also strong ethical questions. These questions have been fuelled by announcements, from private companies in particular, of the possibilities for human cloning. One of these questions relates to the patentability of inventions resulting from this area of research. In Europe this question is linked to the general debate surrounding the patentability of biological materials, such as genomic sequences. Although a large number of applications have been filed these last years, a few patents have already been issued. Some of them have been opposed at the European Patent Office. At the request of the European Commission, the European Group on Ethics (EGE) has prepared an opinion on ethical aspects of patenting inventions resulting from human stem cell research.

scholarly journals Biomimetic cell-adhesive ligand-functionalized peptide composite hydrogels maintain stemness of human amniotic mesenchymal stem cells

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Ling Zhang ◽  
Na Xiong ◽  
Yanfei Liu ◽  
Lili Gan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Three Dimensional ◽  
Phenotypic Characterization ◽  
Expression Levels ◽  
Composite Hydrogels ◽  
Cell Adhesive ◽  
Amniotic Mesenchymal Stem Cells

Abstract In vivo, stem cells reside in a three-dimensional (3D) extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors. Biomimicking of the stem cell−matrix interactions is an ideal approach for controlling the stem cell fate. This study investigates the effects of the incorporation of cell-adhesive ligands in 3D self-assembling peptide hydrogels to modulate stem cell survival, proliferation, maintenance of stemness, and osteogenic differentiation. The results show that the composite hydrogels were non-cytotoxic and effective for maintaining human amniotic mesenchymal stem cell (hAMSC) survival, proliferation and phenotypic characterization. The expression levels of pluripotent markers were also upregulated in the composite hydrogels. Under inductive media conditions, mineral deposition and mRNA expression levels of osteogenic genes of hAMSCs were enhanced. The increasing expression of integrin α- and β-subunits for hAMSCs indicates that the ligand−integrin interactions may modulate the cell fate for hAMSCs in composite hydrogels.

scholarly journals Dynamic regulation of mitochondrial-endoplasmic reticulum crosstalk during stem cell homeostasis and aging

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Weiping Lin ◽  
Shuxun Chen ◽  
Yan Wang ◽  
Ming Wang ◽  
Wayne Yuk-Wai Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Stem Cell ◽  
Functional Properties ◽  
Adult Stem Cells ◽  
Mitochondrial Dynamics ◽  
Cell Aging ◽  
Cell Homeostasis ◽  
Mitochondrial Transfer

AbstractCellular therapy exerts profound therapeutic potential for curing a broad spectrum of diseases. Adult stem cells reside within a specified dynamic niche in vivo, which is essential for continuous tissue homeostatic maintenance through balancing self-renewal with lineage selection. Meanwhile, adult stem cells may be multipotent or unipotent, and are present in both quiescent and actively dividing states in vivo of the mammalians, which may switch to each other state in response to biophysical cues through mitochondria-mediated mechanisms, such as alterations in mitochondrial respiration and metabolism. In general, stem cells facilitate tissue repair after tissue-specific homing through various mechanisms, including immunomodulation of local microenvironment, differentiation into functional cells, cell “empowerment” via paracrine secretion, immunoregulation, and intercellular mitochondrial transfer. Interestingly, cell-source-specific features have been reported between different tissue-derived adult stem cells with distinct functional properties due to the different microenvironments in vivo, as well as differential functional properties in different tissue-derived stem cell-derived extracellular vehicles, mitochondrial metabolism, and mitochondrial transfer capacity. Here, we summarized the current understanding on roles of mitochondrial dynamics during stem cell homeostasis and aging, and lineage-specific differentiation. Also, we proposed potential unique mitochondrial molecular signature features between different source-derived stem cells and potential associations between stem cell aging and mitochondria–endoplasmic reticulum (ER) communication, as well as potential novel strategies for anti-aging intervention and healthy aging.

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

Regeneration of pulp-dentin complex using human stem cells of the apical papilla: in vivo interaction with two bioactive materials

2021 ◽  
Author(s):  
Diana B. Sequeira ◽  
Ana Rafaela Oliveira ◽  
Catarina M. Seabra ◽  
Paulo J. Palma ◽  
Carlos Ramos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Stem Cells ◽  
Bioactive Materials ◽  
Apical Papilla

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.

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