scholarly journals Changes in ionizing radiation dose rate affect cell cycle progression in adipose derived stem cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250160
Author(s):  
Matthew Rusin ◽  
Nardine Ghobrial ◽  
Endre Takacs ◽  
Jeffrey S. Willey ◽  
Delphine Dean
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Radiation Therapy ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Ionizing Radiation ◽  
Dose Rate ◽  
Cell Types ◽  
High Energy ◽  
Adipose Derived Stem Cells

Biomedical use of radiation is utilized in effective diagnostic and treatment tools, yet can introduce risks to healthy tissues. High energy photons used for diagnostic purposes have high penetration depth and can discriminate multiple tissues based on attenuation properties of different materials. Likewise, the ability to deposit energy at various targets within tumors make the use of photons effective treatment for cancer. Radiation focused on a tumor will deposit energy when it interacts with a biological structure (e.g. DNA), which will result in cell kill should repair capacity of the tissue be overwhelmed. Likewise, damage to normal, non-cancerous tissues is a consequence of radiation that can lead to acute or late, chronic toxicity profiles. Adipose derived stem cells (ADSCs) are mesenchymal stem cells that have been proven to have similar characteristics to bone marrow derived stem cells, except that they are much easier to obtain. Within the body, ADSCs act as immunomodulators and assist with the maintenance and repair of tissues. They have been shown to have excellent differentiation capability, making them an extremely viable option for stem cell therapies and regenerative medicine applications. Due to the tissue ADSCs are derived from, they are highly likely to be affected by radiation therapy, especially when treating tumors localized to structures with relatively high ADSC content (eg., breast cancer). For this reason, the purpose behind this research is to better understand how ADSCs are affected by doses of radiation comparable to a single fraction of radiation therapy. We also measured the response of ADSCs to exposure at different dose rates to determine if there is a significant difference in the response of ADSCs to radiation therapy relevant doses of ionizing radiation. Our findings indicate that ADSCs exposed to Cesium (Cs 137)-gamma rays at a moderate dose of 2Gy and either a low dose rate (1.40Gy/min) or a high dose rate (7.31Gy/min) slow proliferation rate, and with cell cycle arrest in some populations. These responses ADSCs were not as marked as previously measured in other stem cell types. In addition, our results indicate that differences in dose rate in the Gy/min range typically utilized in small animal or cell irradiation platforms have a minimal effect on the function of ADSCs. The potential ADSCs have in the space of regenerative medicine makes them an ideal candidate for study with ionizing radiation, as they are one of the main cell types to promote tissue healing.

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

2015 ◽  
Vol 210 (5) ◽  
pp. 717-726 ◽  
Author(s):  
Alice Parisi ◽  
Floriane Lacour ◽  
Lorenzo Giordani ◽  
Sabine Colnot ◽  
Pascal Maire ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Double Knockout ◽  
Muscle Stem Cells ◽  
Adult Muscle ◽  
Canonical Wnt

The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.

scholarly journals Loss of foxo rescues stem cell aging in Drosophila germ line

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Filippo Artoni ◽  
Rebecca E Kreipke ◽  
Ondina Palmeira ◽  
Connor Dixon ◽  
Zachary Goldberg ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Ionizing Radiation ◽  
Cell Injury ◽  
Germ Line ◽  
Adult Stem Cell ◽  
Cell Aging ◽  
Germline Stem Cells ◽  
Cell Cycle Reentry

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.

Stem Cell-Based Personalized Medicine

2012 ◽  
pp. 1855-1866
Author(s):  
Alessandro Prigione
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Personalized Medicine ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Research Field ◽  
Cellular Reprogramming ◽  
Differentiated Cells ◽  
New Therapeutic Approaches

Regenerative medicine is a rapidly evolving research field whose main aims are to provide new therapeutic approaches and to repair or replace injured tissues with functional cells derived from stem cells. In the past few years, research breakthroughs have revolutionized the field by showing that all somatic cells have the potential to re-acquire stem cell-like properties. Thus, it appears possible to generate relevant cell types starting from cells easily obtained from affected individuals. The obtained differentiated cells could eventually serve as in vitro tools for the study of disease-associated mechanisms and for performing customized drug screenings. Moreover, in the context of cellular transplantation, these cells represent the ideal cell source given that they posses the same genetic code and thus will avoid the occurrence of unwanted immune reactions. Overall, this revolutionary technique called cellular reprogramming might provide substantial support for the future development of personalized medicine. In this chapter, I describe the recent advances in the field of stem cell-based regenerative medicine applications. Parkinson’s disease is chosen as a paradigmatic example in which the use of stem cells for study and therapy could have a relevant impact and potentially represent a future cure for this debilitating disorder.

scholarly journals Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Amar M. Singh
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
The Road ◽  
Developmental Factors ◽  
On The Road ◽  
G1 Cells

Cellular heterogeneity is now considered an inherent property of most stem cell types, including pluripotent stem cells, somatic stem cells, and cancer stem cells, and this heterogeneity can exist at the epigenetic, transcriptional, and posttranscriptional levels. Several studies have indicated that the stochastic activation of signaling networks may promote heterogeneity and further that this heterogeneity may be reduced by their inhibition. But why different cells in the same culture respond in a nonuniform manner to the identical exogenous signals has remained unclear. Recent studies now demonstrate that the cell cycle position directly influences lineage specification and specifically that pluripotent stem cells initiate their differentiation from the G1 phase. These studies suggest that cells in G1 are uniquely “poised” to undergo cell specification. G1 cells are therefore more prone to respond to differentiation cues, which may explain the heterogeneity of developmental factors, such as Gata6, and pluripotency factors, such as Nanog, in stem cell cultures. Overall, this raises the possibility that G1 serves as a “Differentiation Induction Point.” In this review, we will reexamine the literature describing heterogeneity of pluripotent stem cells, while highlighting the role of the cell cycle as a major determinant.

scholarly journals Role of Vibrational Spectroscopy in Stem Cell Research

2012 ◽  
Vol 27 ◽  
pp. 167-184 ◽  
Author(s):  
Ceren Aksoy ◽  
Feride Severcan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Vibrational Spectroscopy ◽  
Cell Biology ◽  
Cell Types ◽  
Stem Cell Biology ◽  
Label Free ◽  
Monitoring Methods

Recent researches have mainly displayed the significant role of stem cells in tissue renewal and homeostasis with their unique capacity to develop different cell types. These findings have clarified the importance of stem cells to improve the effectiveness of any cell therapy for regenerative medicine. Identification of purity and differentiation stages of stem cells are the greatest challenges of stem cell biology and regenerative medicine. The existing methods to carefully monitor and characterize the stem cells have some unwanted effects on the properties of stem cells, and these methods also do not provide real-time information about cellular conditions. These challenges enforce the usage of nondestructive, rapid, sensitive, high quality, label-free, cheep, and innovative chemical monitoring methods. In this context, vibrational spectroscopy provides promissing alternative to get new information into the field of stem cell biology for chemical analysis, quantification, and imaging of stem cells. Raman and infrared spectroscopy and imaging can be used as a new complimentary spectroscopic approaches to gain new insight into stem cell reseaches for future therapeutic and regenerative medicines. In this paper, recent developments in applications of vibrational spectroscopy techniques for stem cell characterization and identification are presented.

scholarly journals 167 ISOLATION AND COMPARATIVE PROFILING OF HUMAN ADIPOSE-DERIVED ADULT STEM CELLS

2005 ◽  
Vol 17 (2) ◽  
pp. 234
Author(s):  
A. Boquest ◽  
A. Shahdadfar ◽  
K. Fronsdal ◽  
J. Brinchmann ◽  
P. Collas
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Signaling ◽  
Proliferative Capacity ◽  
Stromal Stem Cells

The stromal compartment of mesenchymal tissues is thought to harbor stem cells that display extensive proliferative capacity and multilineage potential. However, despite their potential impact in the field of regenerative medicine, little is known about the biology of stromal stem cells prior to culture. After removing adipocytes and erythrocytes from collagenase digested human adipose tissue, we identified two cell populations using flow cytometry which shared expression of stem cell markers SH2 and CD34, but lacked the phenotypic characteristics of leukocytes (CD45−). However, they were found to be discernible based on CD31 expression, a marker for endothelial cells. Using CD31 conjugated magnetic beads, we separated these cells (CD45-CD31− and CD45-CD31+) from three patients and compared global gene expression profiles using an Affymetrix platform. The prominant feature of CD45-CD31+ cells was the up-regulation of genes associated with endothelial cells. By contrast, CD45-CD31− cells were found to overexpress transcripts involved in cell cycle quiescence and cell signaling elements including those of the WNT pathway thought to be important for maintaining the stem cell state. Upon culture in DMEM/F12 with 20% FCS, only CD45-CD31− cells were capable of adhering to plastic and forming colonies. These cells with fibroblastic morphology met the key criterion of stem cells, the ability to proliferate while retaining the capacity to differentiate into mature tissues. Under appropriate inductive conditions, they were found to exclusively form bone, cartilage, adipose and neuronal-like tissues in vitro. Clonal cell lines generated from individually cultured CD45-CD31− cells displayed multilineage and proliferative capacity, validating our conclusion that they are true stem cells and not simply committed progenitors. We then undertook extensive comparative profiling of CD45-CD31− cells with their cultured counterparts to examine changes that stromal stem cells undergo during culture. Except for the disappearance of CD34, flow cytometry analysis using 52 antibodies revealed little change in cell surface phenotype as a result of culture. However, comparative global gene profiling revealed extensive down-regulation of many genes during culture. These included cell cycle arresting genes, as expected, and genes encoding elements involved in cell signaling including those belonging to the tumor necrosis factor, interleukin, transforming growth factor and chemokine families. The consequences of these changes remain unknown, but ultimately may affect the potential use of adipose tissue stem cells in regenerative medicine.

scholarly journals Adipose-derived stem cells: a review of osteogenesis differentiation

2016 ◽  
Vol 12 ◽  
pp. 38-47 ◽  
Author(s):  
Aleksandra Skubis ◽  
Bartosz Sikora ◽  
Nikola Zmarzły ◽  
Emilia Wojdas ◽  
Urszula Mazurek
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Cell Types ◽  
Bone Tissue Regeneration ◽  
Adipose Derived Stem Cells

This review article provides an overview on adipose-derived stem cells (ADSCs) for implications in bone tissue regeneration. Firstly this article focuses on mesenchymal stem cells (MSCs) which are object of interest in regenerative medicine. Stem cells have unlimited potential for self-renewal and develop into various cell types. They are used for many therapies such as bone tissue regeneration. Adipose tissue is one of the main sources of mesenchymal stem cells (MSCs). Regenerative medicine intends to differentiate ADSC along specific lineage pathways to effect repair of damaged or failing organs. For further clinical applications it is necessary to understand mechanisms involved in ADSCs proliferation and differentiation. Second part of manuscript based on osteogenesis differentiation of stem cells. Bones are highly regenerative organs but there are still many problems with therapy of large bone defects. Sometimes there is necessary to make a replacement or expansion new bone tissue. Stem cells might be a good solution for this especially ADSCs which manage differentiate into osteoblast in in vitro and in vivo conditions.

scholarly journals Applications, challenges and prospects of mesenchymal stem cell exosomes in regenerative medicine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aysa Rezabakhsh ◽  
Emel Sokullu ◽  
Reza Rahbarghazi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Ethical Issues ◽  
Cell Communication ◽  
Cell Types ◽  
Therapeutic Approaches ◽  
Cell Therapies ◽  
Isolation And Purification ◽  
Direct Cell

AbstractRecent advances in the identification and application of different stem cell types have offered alternative therapeutic approaches for clinicians. The lack of successful engraftment, migration into the injured site, loss of functionality and viability, ethical issues, shortage of donated allogeneic stem cells and the possibility of transmission of infectious are the main challenges associated with direct cell transplantation. The discovery and research on exosomes have led to the rise of hopes for the alleviation of different pathologies in regenerative medicine. Exo are nano-sized extracellular vesicles (40–150 nm) and released by each type. These nanoparticles participate in cell-to-cell communication in a paracrine manner. It is thought that the application of Exo can circumvent several drawbacks related to whole-cell therapies. Because of their appropriate size and stability, Exo are touted as therapeutic bullets transferring signaling factors into the acceptor cells in a paracrine manner. Despite these advantages, technologies associated with Exo isolation and purification are challenging because of heterogeneity in exosomal size and cargo. The lack of standard GMP-grade protocols is the main hurdle that limits the extensive application of Exo in the clinical setting. Here, the authors aimed to inspire a logical and realistic vision about problems associated with Exo application in regenerative medicine.

scholarly journals The concept of radiation-enhanced stem cell differentiation

2015 ◽  
Vol 49 (3) ◽  
pp. 209-216 ◽  
Author(s):  
Adam A. Mieloch ◽  
Wiktoria M. Suchorska
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Ionizing Radiation ◽  
Adult Stem Cells ◽  
P53 Protein ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Directed Differentiation ◽  
The Many

AbstractBackground.Efficient stem cell differentiation is considered to be the holy grail of regenerative medicine. Pursuing the most productive method of directed differentiation has been the subject of numerous studies, resulting in the development of many effective protocols. However, the necessity for further improvement in differentiation efficiency remains. This review contains a description of molecular processes underlying the response of stem cells to ionizing radiation, indicating its potential application in differentiation procedures. In the first part, the radiation-induced damage response in various types of stem cells is described. Second, the role of the p53 protein in embryonic and adult stem cells is highlighted. Last, the hypothesis on the mitochondrial involvement in stem cell development including its response to ionizing radiation is presented.Conclusions.In summary, despite the many threats of ionizing radiation concerning genomic instability, subjecting cells to the appropriate dosage of ionizing radiation may become a useful method for enhancing directed differentiation in certain stem cell types.

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