scholarly journals Vitamin C in Stem Cell Biology: Impact on Extracellular Matrix Homeostasis and Epigenetics

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Cristina D'Aniello ◽  
Federica Cermola ◽  
Eduardo Jorge Patriarca ◽  
Gabriella Minchiotti

Transcription factors and signaling molecules are well-known regulators of stem cell identity and behavior; however, increasing evidence indicates that environmental cues contribute to this complex network of stimuli, acting as crucial determinants of stem cell fate.L-Ascorbic acid (vitamin C (VitC)) has gained growing interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. Here, we review the main functions of VitC and its effects on stem cells, focusing on its activity as cofactor of Fe+2/αKG dioxygenases, which regulate the epigenetic signatures, the redox status, and the extracellular matrix (ECM) composition, depending on the enzymes’ subcellular localization. Acting as cofactor of collagen prolyl hydroxylases in the endoplasmic reticulum, VitC regulates ECM/collagen homeostasis and plays a key role in the differentiation of mesenchymal stem cells towards osteoblasts, chondrocytes, and tendons. In the nucleus, VitC enhances the activity of DNA and histone demethylases, improving somatic cell reprogramming and pushing embryonic stem cell towards the naive pluripotent state. The broad spectrum of actions of VitC highlights its relevance for stem cell biology in both physiology and disease.

2021 ◽  
pp. 1-18
Author(s):  
Ryan S. Stowers

In the fields of regenerative medicine and tissue engineering, stem cells offer vast potential for treating or replacing diseased and damaged tissue. Much progress has been made in understanding stem cell biology, yielding protocols for directing stem cell differentiation toward the cell type of interest for a specific application. One particularly interesting and powerful signaling cue is the extracellular matrix (ECM) surrounding stem cells, a network of biopolymers that, along with cells, makes up what we define as a tissue. The composition, structure, biochemical features, and mechanical properties of the ECM are varied in different tissues and developmental stages, and serve to instruct stem cells toward a specific lineage. By understanding and recapitulating some of these ECM signaling cues through engineered ECM-mimicking hydrogels, stem cell fate can be directed in vitro. In this review, we will summarize recent advances in material systems to guide stem cell fate, highlighting innovative methods to capture ECM functionalities and how these material systems can be used to provide basic insight into stem cell biology or make progress toward therapeutic objectives.


2004 ◽  
Vol 359 (1445) ◽  
pp. 851-856 ◽  
Author(s):  
R. D. McKay

The fundamental basis of our work is that organs are generated by multipotent stem cells, whose properties we must understand to control tissue assembly or repair. Central nervous system (CNS) stem cells are now recognized as a well–defined population of precursors that differentiate into cells that are indisputably neurons and glial cells. Work from our group played an important role in defining stem cells of the CNS. Embryonic stem (ES) cells also differentiate to specific neuron and glial types through defined intermediates that are similar to the cellular precursors that normally occur in brain development. There is convincing evidence that the differentiated progeny of ES cells and CNS stem cells show expected functions of neurons and glia. Recent progress has been made on three fundamental developmental processes: (i) cell cycle control; (ii) the control of cell fate; and (iii) early steps in neural differentiation. In addition, our work on CNS stem cells has developed to a stage where there are clinical implications for Parkinson's and other degenerative disorders. These advances establish that stem cell biology contributes to our understanding of brain development and has great clinical promise.


2017 ◽  
Vol 37 (7) ◽  
pp. 647-660 ◽  
Author(s):  
Saradaprasan Muduli ◽  
Li-Hua Chen ◽  
Meng-Pei Li ◽  
Zhao-wen Heish ◽  
Cheng-Hui Liu ◽  
...  

Abstract The physical characteristics of cell culture materials, such as their elasticity, affect stem cell fate with respect to cell proliferation and differentiation. We systematically investigated the morphologies and characteristics of several stem cell types, including human amniotic-derived stem cells, human hematopoietic stem cells, human induced pluripotent stem (iPS) cells, and embryonic stem (ES) cells on poly(vinyl alcohol) (PVA) hydrogels immobilized with and without extracellular matrix-derived oligopeptide. Human ES cells did not adhere well to soft PVA hydrogels immobilized with oligovitronectin, whereas they did adhere well to PVA hydrogel dishes with elasticities greater than 15 kPa. These results indicate that biomaterials such as PVA hydrogels should be designed to possess minimum elasticity to facilitate human ES cell attachment. PVA hydrogels immobilized with and without extracellular matrix-derived oligopeptides are excellent candidates of cell culture biomaterials for investigations into how cell culture biomaterial elasticity affects stem cell culture and differentiation.


2011 ◽  
Vol 366 (1575) ◽  
pp. 2208-2221 ◽  
Author(s):  
Jem A. Efe ◽  
Sheng Ding

Small molecules have been playing important roles in elucidating basic biology and treatment of a vast number of diseases for nearly a century, making their use in the field of stem cell biology a comparatively recent phenomenon. Nonetheless, the power of biology-oriented chemical design and synthesis, coupled with significant advances in screening technology, has enabled the discovery of a growing number of small molecules that have improved our understanding of stem cell biology and allowed us to manipulate stem cells in unprecedented ways. This review focuses on recent small molecule studies of (i) the key pathways governing stem cell homeostasis, (ii) the pluripotent stem cell niche, (iii) the directed differentiation of stem cells, (iv) the biology of adult stem cells, and (v) somatic cell reprogramming. In a very short period of time, small molecules have defined a perhaps universally attainable naive ground state of pluripotency, and are facilitating the precise, rapid and efficient differentiation of stem cells into somatic cell populations relevant to the clinic. Finally, following the publication of numerous groundbreaking studies at a pace and consistency unusual for a young field, we are closer than ever to completely eliminating the need for genetic modification in reprogramming.


Author(s):  
Jonna Petzold ◽  
Eileen Gentleman

Although understanding how soluble cues direct cellular processes revolutionised the study of cell biology in the second half of the 20th century, over the last two decades, new insights into how mechanical cues similarly impact cell fate decisions has gained momentum. During development, extrinsic cues such as fluid flow, shear stress and compressive forces are essential for normal embryogenesis to proceed. Indeed, both adult and embryonic stem cells can respond to applied forces, but they can also detect intrinsic mechanical cues from their surrounding environment, such as the stiffness of the extracellular matrix, which impacts differentiation and morphogenesis. Cells can detect changes in their mechanical environment using cell surface receptors such as integrins and focal adhesions. Moreover, dynamic rearrangements of the cytoskeleton have been identified as a key means by which forces are transmitted from the extracellular matrix to the cell and vice versa. Although we have some understanding of the downstream mechanisms whereby mechanical cues are translated into changes in cell behaviour, many of the signalling pathways remain to be defined. This review discusses the importance of intrinsic mechanical cues on adult cell fate decisions, the emerging roles of cell surface mechano-sensors and the cytoskeleton in enabling cells to sense its microenvironment, and the role of intracellular signalling in translating mechanical cues into transcriptional outputs. In addition, the contribution of mechanical cues to fundamental processes during embryogenesis such as apical constriction and convergent extension is discussed. The continued development of tools to measure the biomechanical properties of soft tissues in vivo is likely to uncover currently underestimated contributions of these cues to adult stem cell fate decisions and embryogenesis, and may inform on regenerative strategies for tissue repair.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Mina Elahy ◽  
Swati Baindur-Hudson ◽  
Crispin R. Dass

Encoded by a single gene, PEDF is a 50 kDa glycoprotein that is highly conserved and is widely expressed among many tissues. Most secreted PEDF deposits within the extracellular matrix, with cell-type-specific functions. While traditionally PEDF is known as a strong antiangiogenic factor, more recently, as this paper highlights, PEDF has been linked with stem cell biology, and there is now accumulating evidence demonstrating the effects of PEDF in a variety of stem cells, mainly in supporting stem cell survival and maintaining multipotency.


2021 ◽  
Vol 11 (4) ◽  
pp. 1941
Author(s):  
Seungmin Yeom ◽  
Myung Chul Lee ◽  
Shambhavi Pandey ◽  
Jaewoon Lim ◽  
Sangbae Park ◽  
...  

Induced pluripotent stem cells (iPSCs) are a good medicine source because of their potential to differentiate into various tissues or cells. However, traditionally, iPSCs made by specific transgenes and virus vectors are not appropriate for clinical use because of safety concerns and risk of tumor development. The goal of this research was to develop an alternative method for reprogramming, using small molecules and external stimuli. Two groups were established: short-term shear stress (STSS) under suspension culture and a combination of short-term shear stress and vitamin C (SSVC) under suspension culture. For STSS, the pipetting was carried out for cells twice per day for 2 min for 14 days in the embryonic stem cell (ES) medium. In the case of SSVC, the procedure was the same as for STSS however, its ES medium included 10 µM of vitamin C. After 14 days, all spheroids were picked and checked for pluripotency by ALP (alkaline phosphatase) assay and immunocytochemistry. Both groups partially showed the characteristics of stem cells but data demonstrated that the spheroids under shear stress and vitamin C had improved stem cell-like properties. This research showed the possibility of external stimuli and small molecules to reprogram the somatic cells without the use of transgenes.


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