Article Commentary: Stem Cell Research in Cell Transplantation: An Analysis of Geopolitical Influence by Publications

2007 ◽  
Vol 16 (8) ◽  
pp. 867-873 ◽  
Author(s):  
David J. Eve ◽  
Paul R. Sanberg
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Transplantation ◽  
Adult Stem Cells ◽  
Adult Stem Cell ◽  
Therapeutic Area ◽  
Fetal Stem Cells ◽  
Major Player ◽  
The Us ◽  
Restricted Use

One of the fastest growing fields in researching treatments for neurodegenerative and other disorders is the use of stem cells. These cells are naturally occurring and can be obtained from three different stages of an organism's life: embryonic, fetal, and adult. In the US, political doctrine has restricted use of federal funds for stem cells, enhancing research towards an adult source. In order to determine how this legislation may be represented by the stem cell field, a retrospective analysis of stem cell articles published in the journal Cell Transplantation over a 2-year period was performed. Cell Transplantation is considered a translational journal from preclinical to clinical, so it was of interest to determine the publication outcome of stem cell articles 6 years after the US regulations. The distribution of the source of stem cells was found to be biased towards the adult stage, but relatively similar over the embryonic and fetal stages. The fetal stem cell reports were primarily neural in origin, whereas the adult stem cell ones were predominantly mesenchymal and used mainly in neural studies. The majority of stem cell studies published in Cell Transplantation were found to fall under the umbrella of neuroscience research. American scientists published the most articles using stem cells with a bias towards adult stem cells, supporting the effect of the legislation, whereas Europe was the leading continent with a bias towards embryonic and fetal stem cells, where research is “controlled” but not restricted. Japan was also a major player in the use of stem cells. Allogeneic transplants (where donor and recipient are the same species) were the most common transplants recorded, although the transplantation of human-derived stem cells into rodents was the most common specific transplantation performed. This demonstrates that the use of stem cells is an increasingly important field (with a doubling of papers between 2005 and 2006), which is likely to develop into a major therapeutic area over the next few decades and that funding restrictions can affect the type of research being performed.

scholarly journals GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 225
Author(s):  
Claire Racaud-Sultan ◽  
Nathalie Vergnolle
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Glycogen Synthase ◽  
Inflammatory Diseases ◽  
Adult Stem Cell ◽  
Leukemic Cells ◽  
Cell Phenotype ◽  
Epithelial Regeneration ◽  
Cell Functions

In adult stem cells, Glycogen Synthase Kinase 3β (GSK3β) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3β activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin α5β1 or PAR2 activation, a molecular complex is organized around the scaffolding proteins RACK1 and β-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3β activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3β has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR2 activation, whereas formers were protected from cytotoxicity through α5β1 engagement. However, a prolonged activation of GSK3β promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3β-dependent cellular functions. GSK3β activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

scholarly journals Stem Cells: Insights into Niche, Classification, Identification, Characterization, Mechanisms of Regeneration by Using Stem Cells, and Applications in Joint Disease Remedy

2021 ◽  
Vol 2 (1) ◽  
pp. 01-07
Author(s):  
Azab Azab
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Immunosuppressive Therapy ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Joint Disease ◽  
Cartilage Defects ◽  
Germ Layers ◽  
Fetal Stem Cells

Background: Stem cell therapy has attracted much interest in the 21st century, not only because of the controversy surrounding the ethics involving pluripotent stem cells, but their potential for clinical use. Objectives: The present review highlights the stem cells niche, types, identification, and characterization, mechanisms of regeneration by using stem cells, and applications in joint disease remedy. Stem cells could be well differentiated cells with the potential to display different cell types depending on the host niche. Niche is defined as the cellular microenvironment providing support and stimuli to control the properties of stem cells. It consists of signaling molecules, inter-cell contacts and interaction between stem cells and their extracellular matrix neighbors. Stem cells are classified according to their sources into two main types, the embryonic and non-embryonic. Embryonic stem cells are pluripotent and can differentiate into all germ layers. Non-embryonic stem cells can be sub-classified into fetal stem cells and adult stem cells. Cultured cells can be made to differentiate into exclusive lineages by providing selective media components that can be identified by histochemical staining and quantified by quantitative Real-time polymerase chain reaction. Mesenchymal stem cells (MSCs) can be identified based on the expression of specific proteins called surface antigen phenotype of mesenchymal stem cell markers. MSCs secrete a variety of interleukins, several neurotrophic factors, many cytokines, and growth factors. These secreted bioactive factors have both paracrine and autocrine effects, which are anti-fibrotic and anti-apoptotic, as well as enhance angiogenesis. Furthermore, they stimulate mitosis and differentiation of tissue-intrinsic reparative stem cells. Systemic MSC transplantation can engraft to an injured tissue and promote wound healing through differentiation, and proliferation in synergy with hematopoietic stem cells. MSCs have been shown to express a variety of chemokines and chemokine receptors and can home to sites of inflammation by migrating towards injury or inflammatory chemokines and cytokines. MSCs are proven to have immunomodulatory properties that are among the most intriguing aspects of their biology. The immunosuppressive properties of MSCs inhibit the immune response of naive and memory T cells in a mixed lymphocyte culture and induce mitogen. The systemic infusion of MSCs can be used in immunosuppressive therapy of various disorders. MSCs have become an alternative source of cells that can be drawn from several these cells have been used as treatment to repair cartilage defects at early stages sources. Using the MSCs and directing them into chondrogenic differentiation might lead to the formation of higher quality cartilage, which has a great composition of hyaline, adequate structural reorganization and therefore improved biomechanical properties. Conclusion: It can be concluded that stem cells are classified according to their sources into two main types, the embryonic and non-embryonic. Embryonic stem cells are pluripotent and can differentiate into all germ layers. Non-embryonic stem cells can be sub-classified into fetal stem cells and adult stem cells. MSCs secrete bioactive factors that are anti-fibrotic and anti-apoptotic, as well as enhance angiogenesis. The systemic infusion of MSCs can be used in immunosuppressive therapy of various disorders. These cells have been used as treatment to repair cartilage defects at early stages.

scholarly journals Adult stem cell transplantation combined with conventional therapy for the treatment of end-stage liver disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chen-Hui Zhu ◽  
Dian-Han Zhang ◽  
Chen-Wei Zhu ◽  
Jing Xu ◽  
Chuan-Long Guo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Liver Disease ◽  
Liver Function ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Adult Stem Cell ◽  
End Stage Liver Disease ◽  
End Stage

AbstractEnd-stage liver disease (ESLD) is characterized by the deterioration of liver function and a subsequent high mortality rate. Studies have investigated the use of adult stem cells to treat ESLD. Here, a systematic review and meta-analysis was conducted to determine the efficacy of a combination therapy with adult stem cell transplantation and traditional medicine for treating ESLD. Four databases—including PubMed, Web of Science, Embase, and Cochrane Library—were investigated for studies published before January 31, 2021. The main outcome indicators were liver function index, model for end-stage liver disease (MELD) scores, and Child‒Turcotte‒Pugh (CTP) scores. Altogether, 1604 articles were retrieved, of which eight met the eligibility criteria; these studies included data for 579 patients with ESLD. Combination of adult stem cell transplantation with conventional medicine significantly improved its efficacy with respect to liver function index, CTP and MELD scores, but this effect gradually decreased over time. Moreover, a single injection of stem cells was more effective than two injections with respect to MELD and CTP scores and total bilirubin (TBIL) and albumin (ALB) levels, with no significant difference in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. With respect to the TBIL levels, patients receiving mononuclear cells (MNCs) experienced a significantly greater therapeutic effect—starting from twenty-four weeks after the treatment—whereas with respect to ALB levels, CD34+ autologous peripheral blood stem cells (CD34+ APBSCs) and MNCs had similar therapeutic effects. Severe complications associated with adult stem cell treatment were not observed. Although the benefits of combination therapy with respect to improving liver function were slightly better than those of the traditional treatment alone, they gradually decreased over time.Systematic review registration: PROSPERO registration number: CRD42021238576.

scholarly journals Adult Stem Cell Therapeutics in Diabetic Retinopathy

2019 ◽  
Vol 20 (19) ◽  
pp. 4876 ◽  
Author(s):  
Sriprachodaya Gaddam ◽  
Ramesh Periasamy ◽  
Rajashekhar Gangaraju
Keyword(s):  
Stem Cells ◽  
Diabetic Retinopathy ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Adult Stem Cell ◽  
Target Tissue ◽  
Cell Therapeutics ◽  
Potential Safety ◽  
Working Age ◽  
Stem Cell Therapeutics

Diabetic retinopathy (DR), a complication of diabetes, is one of the leading causes of blindness in working-age adults. The pathology of the disease prevents the endogenous stem cells from participating in the natural repair of the diseased retina. Current treatments, specifically stem cell therapeutics, have shown variable efficacy in preclinical models due to the multi-faceted nature of the disease. Among the various adult stem cells, mesenchymal stem cells, especially those derived from adipose tissue and bone marrow, have been explored as a possible treatment for DR. This review summarizes the current literature around the various adult stem cell treatments for the disease and outlines the benefits and limitations of the therapeutics that are being explored in the field. The paracrine nature of adipose stem cells, in particular, has been highlighted as a potential solution to the lack of a homing and conducive environment that poses a challenge to the implantation of exogenous stem cells in the target tissue. Various methods of mesenchymal stem cell priming to adapt to a hostile retinal microenvironment have been discussed. Current clinical trials and potential safety concerns have been examined, and the future directions of stem cell therapeutics in DR have also been contemplated.

scholarly journals Asymmetric Cell Kinetics Genes: The Key to Expansion of Adult Stem Cells in Culture

2002 ◽  
Vol 2 ◽  
pp. 1906-1921 ◽  
Author(s):  
James L. Sherley
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Kinetics ◽  
Embryonic Stem ◽  
Adult Stem Cell ◽  
Cellular Mechanisms ◽  
Cells In Culture ◽  
Somatic Tissues ◽  
Kinetics Of

A singular challenge in stem cell research today is the expansion and propagation of functional adult stem cells. Unlike embryonic stem cells, which are immortal in culture, adult stem cells are notorious for the difficulty encountered when attempts are made to expand them in culture. One overlooked reason for this difficulty may be the inherent asymmetric cell kinetics of stem cells in postnatal somatic tissues. Senescence is the expected fate of a culture whose growth depends on adult stem cells that divide with asymmetric cell kinetics. Therefore, the bioengineering of strategies to expand adult stem cells in culture requires knowledge of cellular mechanisms that control asymmetric cell kinetics. The properties of several genes recently implicated to function in a cellular pathway(s) that regulates asymmetric cell kinetics are discussed. Understanding the function of these genes in asymmetric cell kinetics mechanisms may be the key that unlocks the adult stem cell expansion problem.

scholarly journals Peripheral Nerve Regeneration Using Different Germ Layer-Derived Adult Stem Cells in the Past Decade

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yu Li ◽  
Yuzuru Kamei ◽  
Miki Kambe ◽  
Katsumi Ebisawa ◽  
Mayumi Oishi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Stem Cell ◽  
Peripheral Nerve ◽  
Adult Stem Cells ◽  
Peripheral Nerve Regeneration ◽  
Adult Stem Cell ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
The Past

Peripheral nerve injuries (PNIs) are some of the most common types of traumatic lesions affecting the nervous system. Although the peripheral nervous system has a higher regenerative ability than the central nervous system, delayed treatment is associated with disturbances in both distal sensory and functional abilities. Over the past decades, adult stem cell-based therapies for peripheral nerve injuries have drawn attention from researchers. This is because various stem cells can promote regeneration after peripheral nerve injuries by differentiating into neural-line cells, secreting various neurotrophic factors, and regulating the activity of in situ Schwann cells (SCs). This article reviewed research from the past 10 years on the role of stem cells in the repair of PNIs. We concluded that adult stem cell-based therapies promote the regeneration of PNI in various ways.

scholarly journals Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Menon ◽  
Pasquale Creo ◽  
Marco Piccoli ◽  
Sonia Bergante ◽  
Erika Conforti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Response ◽  
Adult Stem Cells ◽  
Chemical Activation ◽  
Hypoxia Inducible Factor ◽  
Adult Stem Cell ◽  
Dependent Manner

Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

scholarly journals Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sounak Sahu ◽  
Divya Sridhar ◽  
Prasad Abnave ◽  
Noboyoshi Kosaka ◽  
Anish Dattani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Dna Repair ◽  
Stem Cell ◽  
Cell Migration ◽  
Adult Stem Cells ◽  
Adult Stem Cell ◽  
Wound Site ◽  
Stem Cell Migration

Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of Migration-Coupled-DNA-Damage (MCDD) are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represent an unappreciated source of damage, that could be a significant source of mutations in animals during development or during long term tissue homeostasis.

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