scholarly journals Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Silvana Bardelli ◽  
Marco Moccetti
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Translational Medicine ◽  
Process Development ◽  
Therapeutic Potential ◽  
Adult Stem Cell ◽  
Cell Renewal ◽  
Stem Cell Niches

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regenerationin vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizingin vitroorin vivothe various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

scholarly journals Designing stem cell niches for differentiation and self-renewal

2018 ◽  
Vol 15 (145) ◽  
pp. 20180388 ◽  
Author(s):  
Hannah Donnelly ◽  
Manuel Salmeron-Sanchez ◽  
Matthew J. Dalby
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Regulatory Networks ◽  
Regulatory Mechanisms ◽  
Great Promise ◽  
Regenerative Capacity ◽  
Cell Niche ◽  
Stem Cell Niches

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche . Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro . In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.

Designing and Engineering Stem Cell Niches

MRS Bulletin ◽  
2010 ◽  
Vol 35 (8) ◽  
pp. 591-596 ◽  
Author(s):  
Ana I. Teixeira ◽  
Ola Hermanson ◽  
Carsten Werner
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Chemical Engineering ◽  
Polyglycolic Acid ◽  
Differentiated Cells ◽  
Extracellular Matrix Components ◽  
Stem Cell Niches

AbstractStem cells have received a lot of attention due to great promises in medical treatment, for example, by replacing lost and sick cells and re-constituting cell populations. There are several classes of stem cells, including embryonic, fetal, and adult tissue specific. More recently, the generation of so-called induced pluripotent stem (iPS) cells from differentiated cells has been established. Common criteria for all types of stem cells include their ability to self-renew and to retain their ability to differentiate in response to specific cues. These characteristics, as well as the instructive steering of the cells into differentiation, are largely dependent on the microenvironment surrounding the cells. Such “stem cell friendly” microenvironments, provided by structural and biochemical components, are often referred to as niches. Biomaterials offer attractive solutions to engineer functional stem cell niches and to steer stem cell state and fatein vitroas well asin vivo. Among materials used so far, promising results have been achieved with low-toxicity and biodegradable polymers, such as polyglycolic acid and related materials, as well as other polymers used as structural “scaffolds” for engineering of extracellular matrix components. To improve the efficiency of stem cell control and the design of the biomaterials, interfaces among stem cell research, developmental biology, regenerative medicine, chemical engineering, and materials research are rapidly developing. Here we provide an introduction to stem cell biology and principles of niche engineering and give an overview of recent advancements in stem cell niche engineering from two stem cell systems—blood and brain.

scholarly journals Impedance-based cellular assays for regenerative medicine

2018 ◽  
Vol 373 (1750) ◽  
pp. 20170226 ◽  
Author(s):  
W. Gamal ◽  
H. Wu ◽  
I. Underwood ◽  
J. Jia ◽  
S. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Large Scale ◽  
Three Dimensional ◽  
Cell Renewal ◽  
Label Free ◽  
Impedance Tomography ◽  
Cellular Assays ◽  
Automation And Control

Therapies based on regenerative techniques have the potential to radically improve healthcare in the coming years. As a result, there is an emerging need for non-destructive and label-free technologies to assess the quality of engineered tissues and cell-based products prior to their use in the clinic. In parallel, the emerging regenerative medicine industry that aims to produce stem cells and their progeny on a large scale will benefit from moving away from existing destructive biochemical assays towards data-driven automation and control at the industrial scale. Impedance-based cellular assays (IBCA) have emerged as an alternative approach to study stem-cell properties and cumulative studies, reviewed here, have shown their potential to monitor stem-cell renewal, differentiation and maturation. They offer a novel method to non-destructively assess and quality-control stem-cell cultures. In addition, when combined with in vitro disease models they provide complementary insights as label-free phenotypic assays. IBCA provide quantitative and very sensitive results that can easily be automated and up-scaled in multi-well format. When facing the emerging challenge of real-time monitoring of three-dimensional cell culture dielectric spectroscopy and electrical impedance tomography represent viable alternatives to two-dimensional impedance sensing. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’.

scholarly journals A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis

2017 ◽  
Author(s):  
Ajay Mishra ◽  
Angela Oliveira Pisco ◽  
Benedicte Oules ◽  
Tony Ly ◽  
Kifayathullah Liakath-Ali ◽  
...  
Keyword(s):  
Stem Cell ◽  
Terminal Differentiation ◽  
Human Keratinocytes ◽  
Cell Renewal ◽  
Stable States ◽  
Primary Human Keratinocytes ◽  
Network Modelling ◽  
Epidermal Homeostasis

AbstractEpidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation1,2. While progress has been made in characterising the stem and differentiated cell compartments3, the transition between the two cell states, termed commitment4, is poorly understood. Here we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension for up to 12h. We have previously shown that commitment begins at approximately 4h and differentiation is initiated by 8h5. We find that cell detachment induces a network of protein phosphatases. The pro-commitment phosphatases – including DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA – promote terminal differentiation by negatively regulating ERK MAPK and positively regulating key API transcription factors. Their activity is antagonised by concomitant upregulation of the anti-commitment phosphatase DUSP10. The phosphatases form a dynamic network of transient positive and negative interactions, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem cell and differentiated cell) via an unstable (committed) state. In addition phosphatase expression is spatially regulated relative to the location of stem cells, both in vivo and in response to topographical cues in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.

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. .

scholarly journals Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+hMSCs

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Schade ◽  
Paula Müller ◽  
Evgenya Delyagina ◽  
Natalia Voronina ◽  
Anna Skorska ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Nucleic Acid Delivery ◽  
Innovative Strategies ◽  
Genetic Modifications ◽  
Microrna Delivery ◽  
Magnetic Vectors

Genetic modifications of bone marrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to improve their therapeutic potential and enable innovative strategies in tissue regeneration. However, most of the studies use cultured hMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR carrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated hMSCs. MNP based transfection is preferable for genetic modificationsin vivodue to improved selectivity, safety of delivery, and reduced side effects. Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were testedin vitrofor uptake efficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes were selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag). We found that all tested transfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become crucial for virus-free introduction of therapeutic miRs as well as other nucleic acidsin vivo. Moreover, in the field of targeted stem cell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulationin vitro.

scholarly journals The Human Skin-Derived Precursors for Regenerative Medicine: Current State, Challenges, and Perspectives

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ru Dai ◽  
Wei Hua ◽  
Heng Xie ◽  
Wei Chen ◽  
Lidan Xiong ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Adult Stem Cell ◽  
Biological Properties ◽  
Culture Methods ◽  
Stem Cell Source ◽  
Cell Based Therapy ◽  
Potential Applications ◽  
Innovative Culture

Skin-derived precursors (SKPs) are an adult stem cell source with self-renewal and multipotent differentiation. Although rodent SKPs have been discussed in detail in substantial studies, human SKPs (hSKPs) are rarely reported. Understanding the biological properties and possible mechanisms underlying hSKPs has important implications for regenerative medicine particularly clinical applications, as human-derived sources are more suitable for clinical transplantation. The finding that hSKPs derivatives, such as neural and mesodermal progeny, have bothin vitroandin vivofunction without any genetical modification makes hSKPs a trustable, secure, and accessible resource for cell-based therapy. Here, we provide an overview of hSKPs, describing their characteristics, originations and niches, and potential applications. A comparison between traditional and innovative culture methods used for hSKPs is also introduced. Furthermore, we discuss the challenges and the future perspectives towards the field of hSKPs. With this review, we hope to point out the current stage of hSKPs and highlight the problems that remain in this field.

scholarly journals Metabolic Requirements for Spermatogonial Stem Cell Establishment and Maintenance In Vivo and In Vitro

2021 ◽  
Vol 22 (4) ◽  
pp. 1998
Author(s):  
Anna Laura Voigt ◽  
Shiama Thiageswaran ◽  
Nathalia de Lima e Martins Lara ◽  
Ina Dobrinski
Keyword(s):  
Stem Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Adult Stem Cell ◽  
Spermatogonial Stem Cell ◽  
Testicular Development ◽  
Cell Integrity ◽  
In Vitro Expansion

The spermatogonial stem cell (SSC) is a unique adult stem cell that requires tight physiological regulation during development and adulthood. As the foundation of spermatogenesis, SSCs are a potential tool for the treatment of infertility. Understanding the factors that are necessary for lifelong maintenance of a SSC pool in vivo is essential for successful in vitro expansion and safe downstream clinical usage. This review focused on the current knowledge of prepubertal testicular development and germ cell metabolism in different species, and implications for translational medicine. The significance of metabolism for cell biology, stem cell integrity, and fate decisions is discussed in general and in the context of SSC in vivo maintenance, differentiation, and in vitro expansion.

scholarly journals Stemness specificity of epithelial cells – application of cell and tissue technology in regenerative medicine

2018 ◽  
Vol 6 (3) ◽  
pp. 114-119 ◽  
Author(s):  
Magdalena Rojewska ◽  
Małgorzata Popis ◽  
Maurycy Jankowski ◽  
Dorota Bukowska ◽  
Paweł Antosik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
The Body ◽  
Current Evidence ◽  
Epithelial Tissue

AbstractStem cells are cells that have the potential to replicate and/or differentiate, becoming any tissue. This process could be theoretically repeated indefinitely and can be used to create or fix damaged parts any organ. There are many in vivo factors that cause stem cells to replicate and differentiate. Many of these interactions and mechanisms are still unknown. In vitro models have been successful in inducing stem cells to differentiate into the desired lineage using controlled methods. Recently, epithelial tissue has been successfully created using scaffolds on which stem cells are grown in vitro and then transplanted into the host. This transition creates significant problems. This is because in vitro -grown stem cells or stem cell-derived tissues are created in an isolated environment where virtually every aspect can be monitored and controlled. In vivo monitoring and controlling is significantly more difficult for a plethora of reasons. Cells in the body are constantly exposed to many signals and molecules which affect them. Many of the mechanisms behind these interactions and reactions are known but many others are not. As the corpus of knowledge grows, stem cells become closer to being applied in a clinical setting. In this paper, we review the current evidence on stem cell therapy in regenerative medicine and some of the challenges this field faces.

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