Search results for “stem cell”

Ethics of Modern Stem Cell Research and Therapy: Current Critical and Interdisciplinary Perspectives

From an academic and clinical point of view, stem cell therapy represents one of the most promising advances in modern medicine, with the ability to partially induce the regeneration of acutely injured or chronically damaged tissues. Stem cell research provides new opportunities for the treatment of various conditions, among them diabetes mellitus, HIV, cardiovascular diseases, and neurodegenerative illnesses. Stem cell therapy is currently not FDA-approved in the US (except for certain blood cancers). While bioethics and religion have mostly discussed the source of cells, i.e., embryonic cells that require the destruction of embryos versus adult tissue for research purposes, we also discuss the controversies with regard to currently offered therapies, and marketing of unapproved procedures from a scientific, clinical, and religious viewpoint.

RETRACTED: Leap into Fetal Surgery; In Utero Placental Mesenchymal Stem Cell Therapy, A Contemporary Approach to Treating Myelomeningocele

This article has been retracted on April 10, 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2997-2086.jfs-25-5857) Myelomeningocele (MMC), a class of spina bifida is a type of neural tube defect. According to the U.S. Centers for Disease Control and Prevention, each year approximately 1,400 babies born in the United States have spina bifida. The disease manifests with the lack of skin and bone covering the caudal part of the spinal cord. The patient developing such a condition often develops lifelong impaired lower limb mobility accompanied by hydrocephalus, and urinary and bowel incontinence. The available interventions include prenatal and postnatal surgery to fuse the dura. Prenatal surgery performed before 26 weeks of gestation reduces the risk of death or the need for ventriculoperitoneal shunting. It also enhanced results on a comprehensive index for mental and motor function. When compared to postnatal surgery, prenatal surgery reduces the manifestation of several secondary outcomes, including the degree of hindbrain herniation seen in the Chiari II malformation. Stem cell therapy for MMC on animal models of chick, ovine, and rodents with reported cases 15/63, 15, and 136, respectively, using human Embryonic Stem Cells (hESCs), Neural Stem Cells (NSCs), Mesenchymal Stem Cells (MSCs) showed significant coverage of MMC defect and slight neurogenesis was also observed. With an understanding of medical literature about in-utero regenerative capacity, it is to be appreciated that placental stem cells surgically seeded within a biocompatible scaffold of the cell patches can play a part in alleviating the spinal cord manifestation associated with MMC. Documented animal studies show that incorporating Placental Mesenchymal Stem Cells in prenatal surgery has reported improved neurogenesis and lower limb mobility. In an ovine myelomeningocele model, the development of in-utero myelomeningocele repair with human Placental Mesenchymal Stem Cells seeded onto an extracellular matrix (PMSC-ECM) enhances motor findings. The clinical trial for the first stem cell therapy on human subjects known as the “CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele.” is expected to be finished by 2030. So far, the cases undergoing treatment have shown significant leg movement and a greater degree of bowel and urinary control. This FDA-approved clinical trial is envisioned to be the future of treating MMC.

Retraction Note: Leap into Fetal Surgery; In Utero Placental Mesenchymal Stem Cell Therapy, A Contemporary Approach to Treating Myelomeningocele

Evaluation of A Nutrition Feeding Algorithm for Children and Adolescents Undergoing Haematopoietic Stem Cell Transplantation (HSCT)

Background Nutrition support during the acute phase post allogeneic haematopoietic stem cell transplantation (HSCT) is required to optimise short- and long-term outcomes for children. An algorithm was developed and evaluated to assist clinicians to make objective and consistent enteral feeding decisions. Methods The algorithm was evaluated on all patients who underwent allogeneic HSCT treatment between November 2017 - February 2019. Results Of the 48 patients, 43 had a nasogastric tube (NGT) inserted, of which 36 patients received a hydrolysed peptide-based formula, 5 patients received a whole protein formula only and 2 patients were fed an amino acid-based formula. Parenteral nutrition (PN) was used in 41 of the patients. Eleven did not have an NGT in-situ at the commencement of HSCT. Of the remaining 37 patients, 26 followed the algorithm and 11 patients did not comply. The group of patients who did not follow the algorithm had the longest median length of stay (LOS) of 49 days. Patients receiving only EN had the lowest median LOS of 30 days. The two groups that reported better weight outcomes were those who followed the algorithm and those who were fully EN fed. Conclusions Effective use of the HSCT feeding algorithm indicated improved patient outcomes for children undergoing HSCT, with better weight outcomes and reduced LOS. Recommendations to improve the efficacy and compliance of the algorithm include regular education/input to the oncology medical teams to better understand objective thresholds for EN and PN commencement.

Stem Cell Differentiation Stage Factors (SCDSFs) Taken from Zebrafish Embryo during Organogenesis and their Role as Epigenetics Regulators able to Reverse Neurosensory Hearing Loss

This translational paper discusses differentiation‑stage factors from zebrafish embryos as epigenetic regulators with potential to reverse neurosensory hearing loss. It outlines experimental evidence, delivery concepts, and research gaps.

Therapeutic Potential of Autologous Adipose Derived Mesenchymal Stem Cells in Human POI and Ovarian Aging

Background Women play an important role in the work setting. This leads them to put off their motherhood, sometimes preventing them from getting pregnant. Delaying pregnancy face women with low ovarian response, such as in Premature Ovarian Insufficiency (POI) or Ovarian Aging (OA). There is no current treatment, although there is evidence of improving ovarian function by inyecting mesenchymal stem cells (MSC). Materials and Methods Prospective, observational study of 17 women who attended Pronatal Clinic from 2019 to 2020. Each patient was registered in Assisted Reproductive Treatment (ART) and was enrolled in ovarian treatment with an autologous adipose tissue Mesenchymal Stem Cell (AD-MSCs) protocol. Three groups were assembled: 1) Control: AMH >1.2 ng/mL, without AD-MSCs, 2) POI/OA: female infertility due to POI/OA with AMH <1.2 ng/mL and 3) Amenorrhea: female infertility due to POI/OA with amenorrhea and AMH <1.2 ng/mL. Variables: Age, weight, height, serum AMH, endometrial thickness, follicular size and number on day 2 and 11 of the menstrual cycle, oocyte number, number of blastocysts and pregnancy rate. Results Between month 2 and 5, after AD-MSCs inyection, POI/OA group showed an increase in follicle number (2 to 9) and size (13.5 to 15.5 mm) on day 11 of the menstrual cycle, which resulted in a higher number of MII oocytes (2.6 to 4.2), and an increase in number of blastocysts (0 to 3) and endometrial thickness (8.6 to 9.4). Regarding the Amenorrhea group, a reboot in menstrual cycle was observed, although no further development of blastocyst was found. Conclusion The AD-MSCs inyection directly in the ovary allowed an increase in number of blastocysts and improved pregnancy rates in POI/OA patients.

Effect of Bone Marrow and Adipose Mesenchymal Stem Cells on Rat Intestinal Injury Induced by Methotrexate

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury.

Assessment of Energy of Consciousness Healing on Cell Growth of Plant Stem Cells Callus Culture

The present study was aimed to evaluate the effect of Consciousness Energy Healing Treatment on plant callus of Mandukparni (Centellaasiatica), Katsarika (Barleriacristata), and Amla (Phyllanthus emblica) in Murashige & Skoog liquid medium (MS) for its growth and yield on day 7. The plant callus of all the three plants were divided into two parts, one part received Biofield Energy Treatment remotely (known as The Trivedi Effect®-Energy of Consciousness Healing Treatment) by a renowned Biofield Energy Healer, Gopal Nayak and denoted as Biofield Energy Treated group, while another part did not receive any treatment and defined as control. Plants callus were observed on day 7 after treatment and visualized under phase contrast microscope for cell growth, captured photomicrographs along with wet weight compared with day 0. Results suggested that three plants viz. Mandukparni, Katsarika, and Amla callus after 7 days showed a significant improved growth rate as compared with the respective untreated groups. The weight of the callus growth (in mg) after Biofield Energy Treatment among Mandukparni, Katsarika, and Amla callus on day 7 was 630, 782, and 920 mg, respectively. However, the percentage increase in weight of the callus in Mandukparni, Katsarika and Amla was 11.1%, 52.4%, and 68.5%, respectively than untreated. Hence, results concluded a significant growth in callus weight after Biofield Energy Treatment, which suggested the action as complementary and alternate approach in order to produce most high-value phytoconstituents from plant callus that can be used for making various drugs, food flavoring and colouring agents.

Cancer Stem Cells: A Cause or A Consequence of Field Cancerization

A review discusses the relationship between cancer stem cells and field cancerization, considering bidirectional influences and implications for prevention and targeted therapy.

Successful Allogeneic Hematopoietic Stem Cell Transplantation from A 5/10 Mismatched Unrelated Donor in A Patient with Donor-Specific Anti-HLA Antibodies.

Hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor, an haploidentical donor or a cord blood unit (CBU) has become a widely aviable approach if patient lacks a matched related or unrelated donor. However, if the patient has anti-HLA antibodies against antigens present in the mismatched donor or CBU (donor-specific antibodies, DSAs) this option should be disregarded due to the high risk of graft failure. Desensitization can be used to reduce levels of DSAs but this technique has limited results. We report the case of a 62-year-old woman with DSAs against two haploidentical familiar donors who failed desensitization of DSAs. Finally she underwent a HSCT from a 5/10 mismatched unrelated donor which has been successful.

Expression of Estrogen Receptor β in Hypothalamic Stem Cells

Neural stem cell activity at least partially accounts for the postweaning development of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and estrogen selectively mobilizes neural stem cells in the 3rd ventricle stem cell niche (3VSCN). Here, we examined the expression of estrogen receptor β (ERβ) in the SDN-POA and the 3VSCN. A subset of cells within the SDN-POA--delineated with or without calbindin D28K (CB28)-immunoreactivity (ir)--exhibited ERβ-ir. The ependymal cells that expressed nestin within the 3VSCN also expressed ERβ. Interestingly, a few proliferating (Ki67 positive) cells within the 3VSCN and the hypothalamic parenchyma, including the SDN-POA, displayed ERβ-ir. In parallel, a subset of cells in the subventricular zone was double-labeled with nestin and ERβ or Ki67 and ERβ while the subgranular zone exhibited few such double-labeled cells. ERβ is expressed in hypothalamic stem cells that may regulate cell regenerative cycles.

The Effect of HLA-DRB1 Allele Mismatch on the Results after Hematopoietic Stem Cell Transplantation

This article examines how HLA‑DRB1 allele mismatching influences outcomes after hematopoietic stem cell transplantation. It reviews graft‑versus‑host disease risk, engraftment, and survival metrics in the context of donor matching strategies. The findings support careful allele‑level typing to optimize donor selection and improve post‑transplant prognosis.

Dual Effects of Neuroprotection and Neurotoxicity by General Anesthetics on Neural Stem Cells: Role of Autophagy

General anesthetics (GAs) are widely used for various essential surgical or medical procedures. Recent studies implicate the GAs has dual effects of neuroprotection and neurotoxicity on neurogenesis with unclear mechanisms. This minireview summarizes recent studies on GAs mediated effects on neurogenesis and proposed mechanisms, with focus on autophagy regulation and intracellular calcium homeostasis.

Emerging Paradigms in Regenerative Medicine: Stem cell Therapies

Stem cell research is now emerging as most exciting and promising area of modern biomedical research which has enormous potential for easing suffering for many diseases such as Parkinson’s, Alzheimer’s, Diabetes,Cancer and many more. This is now recognized most promising alternate therapeutic choice for some of the diseases which currently have no other option of an effective therapy. The Stem cell therapy is now strengthened by cutting- edge technologies and rigorous standards of clinical research thus rapidly progressed from bench to the clinic.

Human Umbilical Cord-Derived Mesenchymal Stem Cells as a Source of Odontoblasts: a GMP-compliant Approach

Stem cell-based regenerative therapy can be considered an innovative approach for curing dental caries. Pulp stem cells from human exfoliated deciduous teeth (SHEDs) represent a source of committed cells for generating odontoblasts in vitro; however, SHEDs are not easy to obtain and are limited in quantity. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered to be adult stem cells that can be easily obtained in large numbers. Here, SHEDs and UC-MSCs were conditioned in custom-made serum-free culture media in order to induce differentiation towards odontoblasts. SHEDs and UC-MSCs were expanded in vitro and differentiated into odontoblasts for 21 days using a medium containing transforming growth factor-β (TGF-b3), hepatocyte growth factor (HGF) and growth differentiation factor 5 (GDF5). The ability to induce odontoblast differentiation with a straightforward clinical protocol in compliance with good manufactoring practice (GMP), which avoids animal reagents, and uses unrelated stem cells of unrestricted availability, may be a first step towards a new innovative approach for dentin regeneration.

Immune Thrombocytopenia after Allogeneic Stem Cell Transplantation: Case Report and Brief Overview of Treatment Strategies

Immune thrombocytopenia (ITP) is a rare but well-recognized post-allogeneic hematopoietic stem cell transplant (HSCT) autoimmune complication for which a standard treatment approach is lacking. Herein we report on an adult patient affected by high-risk acute myeloid leukemia (AML) who developed a post-HSCT ITP. Due to the refractoriness to first-line therapies the patient underwent the thrombopoietin (TPO) mimetic Eltrombopag obtaining the ITP resolution. We also discuss the clinical course of ITP in post-HSCT setting and pros and cons of different therapeutic strategies, focusing on the emerging role of TPO mimetics.

Biocompatible Scaffolds for Human-Induced Pluripotent Stem Cell Transplantation and Modeling Post-Stroke Recovery in Three-Dimensional Neural Cell Culture

Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.

Evaluating Circadian Oscillators in Cancer Stem Cells

Cancer is influenced by the ability of cells to maintain circadian rhythms in molecular and metabolic processes. Disturbance of the underlying circadian timing mechanism in circadian clock cells leads to a higher frequency and more rapid progression of cancer. Cancer stem cells with properties of embryonic and somatic stem cells have been implicated as tumor initiators in several types of cancers. Although tumors are reported to have disorganized circadian rhythms, evidence of in vitro circadian rhythms in cancer stem cells of gliomas was recently presented. The possibility and consequences of circadian clocks functioning in cancer stem cells within tumors is examined, and the possible benefits to these cells from circadian timing is discussed in relation to cancer treatments.

Evaluating the Role and Efficacy of Plerixafor in Rescue Mobilization of Autologous Peripheral Blood Stem Cells

In autologous hematopoietic stem cell transplantation patients for whom granulocyte-colony stimulating factor fails to mobilize a sufficient number of peripheral blood stem cells, plerixafor proposes an option for successful rescue mobilization. This paper evaluates the efficacy of plerixafor to mobilize peripheral blood stem cells (PBSCs) in patients who failed previous mobilization with G-CSF alone, by retrospectively analysing the PBSC results from lymphoma and myeloma (MM) patients between 2006 and 2011. Patients were classified according to the CD34+ cells/kg yield collected by apheresis: < 2 x 106 CD34+ cells/kg was considered collection failure, whereas ≥ 5 x 106 CD34+ cells/kg was considered good mobilization. 797 patients underwent one or more apheresis. The first mobilization success rate was 82%; 140 patients proved to be poor mobilizers. Suboptimal first mobilization was significantly associated with age >50 years (p=0.005) and the absence of chemotherapy in prior PBSCs stimulation (p=0.04). 149 rescue protocols were used in the 140 poor mobilizers, and 71 patients received plerixafor. In univariate analysis the remobilization rate without plerixafor was 42% and increased to 65% when plerixafor was added. In multivariate analysis, plerixafor administration reduced the PBSC remobilization failure risk by a half (OR=0.47). The median value of CD34+ cells/kg in transplants increased from 1.43 (range, 014.03) without plerixafor to 3.85 (range, 0–18.25; p=1 x 10-4) with plerixafor. There were more good mobilizers after plerixafor use (35% with plerixafor versus 15% without plerixafor; p=0.005). Plerixafor efficacy was similar for lymphoma (60% remobilization) and MM (80%; p=0.12). These data show that plerixafor was effective in poor mobilizers and that it synergized with G-CSF to improve the quantity of collected PBSCs. Plerixafor also increased transplant feasibility by 23%. While the clinical results of this study are promising, economic data were not taken into account and there is a need for real work concerning the cost-effectiveness of this treatment. We propose a subsequent study in which the economic efficacy of plerixafor’s use is evaluated based on the financial aspects of the treatments received by the cohort evaluated in this paper.

Laryngeal Tissue Engineering using Rabbit Adipose Derived Stem Cells in Fibrin: A Pre-Clinical Model

Vocal fold scarring is a clinical problem without reliable treatment. Tissue engineering of a vocal fold replacement is an exciting potential treatment for vocal fold scars that involve multiple layers of the vocal fold. Human adipose-derived stem cells (ASC) were previously used to produce a promising vocal fold cover layer replacement. However, relevant in vivo studies are needed before human application, and implanting the human cells in animal larynges would introduce significant risk and data confounding. We therefore report here the development of a construct based on rabbit ASC with the potential for use in pre-clinical implantation studies. Rabbit ASC were isolated and cultured in a three-dimensional fibrin matrix to create an implantable construct resembling the vocal fold mucosa. Key differences between the human cell and the rabbit cell models are highlighted.

RETRACTED: A Microglia Initiated Target Therapy in Neuroinflammation for Alzheimer’s Patients

This article has been retracted on 20 March 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2998-4211.jalr-25-5855) The research is focused on neuroinflammation a normal physiological process which is known to be associated with neurodegenerative diseases could be the potential targeted therapy via the microglia cells, it starts with defining Alzheimer’s; a neurodegenerative disease which causes deposition of Aβ (amyloid beta) protein in the cerebral cortex as well as NFT (neurofibrillary tangles) in the hippocampus and basal ganglia. The paper then describes process of neuroinflammation, microglia’s role, apolipoprotein E4 gene in relation to Alzheimer’s, which leads to different stem cell research and how pruning microglia as well as targeting microglia receptors in the brain is being used in current research trials, we included multiple meta-analysis showing microglia receptors being targeted currently by emerging drugs like propofol, antibodies CSF1R inhibitor etc, which are currently under trial phase, the research ends with concluding potential diagnostic markers like sirt1 considered to be an anti-aging protein which can be used as therapeutic interventions and Lps effect on Sirt 1. A Microglia initiated target therapy in Neuroinflammation for Alzheimer’s Patients.

Evolution of the Solid Human Tumor Cells Properties in Various Experimental Systems in Vitro

Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.

Cell Therapy as an Alternative approach for COVID-19 Infection Consequences: A Non-Systematic Review

The current uncontrollable outbreak of novel coronavirus (COVID-19) has unleashed severe global consequences in all aspects of life and society, bringing the whole world to a complete halt and has modeled significant threats to the global economy. The COVID-19 infection manifests with flu-like symptoms such as cough, cold, and fever resulting in acute respiratory distress syndrome (ARDS), lung dysfunction, and other systemic complications in critical patients are creating panic across the globe. However, the licensed vaccine has started to show up; some resulted in side effects that would limit its possibility in some circumstances as allergic personnel, for example. Moreover, the production and approval of new drugs is a very complicated process and takes a long time. On the other hand, stem cells have gone the extra mile and intensively investigated at preclinical and clinical studies in various degenerative diseases, including infectious ones. Stem cells are proposed as a broad-spectrum therapeutic agent, which may suppress the exaggerated immune response and promote endogenous repair by enhancing COVID-19 infected lung microenvironment. Also, stem cells have different application manners, either direct transplantation, exosome transplantation, or drug delivery of specific cytokines or nanoparticles with antiviral property by engineering stem cells. This review discusses and summarizes the possible emerging role of cell-based therapy, especially stem cell therapy, as an alternative promising therapeutic option for the treatment and control of novel COVID-19 and its potential role in tissue rejuvenation after COVID-19 infection.

The Mechanism of Decline of Senescent Skeletal Muscle Satellite Cell Self-Renewal and Regenerative Proliferation: The Role of Heparan Sulfate-FGF-2--FGFR1-p38αMAPK Axis, Sprouty1, miR-1, miR-133 and miR-29a

Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344

The Anemone, The Porcupine: Hairy Cell Leukaemia

Theobjective of reviewing Hairy Cell Leukaemia may be achieved by emphasising the condition as a category of chronic lymphocytic leukaemia with hair like protrusions of the cytoplasm situated on the aberrant B cell surface. An infrequent disorder, hairy cell leukaemia contributes an estimated 2% of lymphoid malignancies with a male predominance ( M:F ::4-5:1). A majority (90%) of instances depict a mutant immunoglobulin heavy chain variable region (IGHV). The haematopoietic stem cells (HSCs) elucidate a B raf proto-oncogene( BRAF V600E gene- 7q34). An enlarged spleen may be discerned along with pancytopenia as a presenting symptom. The morphology of specific hairy cell leukaemia may be on account of an in vitro interaction of primary hairy cells with BRAF genes and MEK inhibitors, which incite a prominent MEK - ERK dephosphorylation, thereby curtailing transcriptional outpourings of the RAS- RAF- MEK-ERK pathway. Bone marrow aspiration or bone marrow trephine biopsy may be inadequate for diagnosis in 30%-50% individuals on account of extensive fibrosis and the bone marrow sections depict a characteristic interstitial infiltration of leukaemia cells.. Reticulin stains exhibit broad, dense reticulum fibres surrounding the individual or aggregates of leukaemia cells with fibrotic extensions into the abutting bone marrow. The immune reactivity of classic hairy cell leukaemia is concurrent CD19+ CD20+,CD 11c+, CD25+, CD103+ and CD123+. Immune staining for CD20+, annexin 1 and VE1 (a BRAF V600E stain) validates the diagnosis and analyses the extent of malignant bone marrow infiltration. Application of inhibitors of BRAF V600E gene is efficacious in patients resistant to standard therapy. An enlarged spleen beyond 3 centimetres of the left costal margin, a white blood cell count greater than 10000 cells/µL , circulating hairy cells in the peripheral blood greater than 5000 cells/µL and a β 2 micro-globulin level exceeding twice the normal range of 3 µg/ml delineate an inferior outcome with resistance to purine analogues (PNAs). CD38+ elucidation ensures a worse prognosis as does the lack of an IGHV mutation with a reduced overall survival,. A lack of BRAF genetic mutation in 10% -20% of hairy cell leukaemia comprises of inferior prognosis.

Calcium Orthophosphate (CaPO4) Scaffolds for Bone Tissue Engineering Applications

The chemical and structural similarities of calcium orthophosphates (abbreviated as CaPO4)to the mineral composition of natural bones and teeth have made them a good candidate for bone tissue engineering applications. Nowadays, a variety of natural or synthetic CaPO4-based biomaterials is produced and has been extensively used for dental and orthopedic applications. Despite their inherent brittleness, CaPO4 materials possess several appealing characteristics as scaffold materials. Namely, their biocompatibility and variable stoichiometry, thus surface charge density, functionality and dissolution properties, make them suitable for both drug and growth factor delivery. Therefore, CaPO4, especially hydroxyapatite (HA) and tricalcium phosphates (TCPs), have attracted a significant interest in simultaneous use as bone grafts and drug delivery vehicles. Namely, CaPO4-based three-dimensional (3D) scaffolds and/or carriers have been designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various types of drugs, biologically active molecules and/or cells. Over the past few decades, their application as bone grafts in combination with stem cells has gained much importance. This review discusses the source, manufacturing methods and advantages of using CaPO4 scaffolds for bone tissue engineering applications. Perspective future applications comprise drug delivery and tissue engineering purposes.

Molecular and Cell Biological Considerations in the Initiation and Development of Sporadic Non-Hereditary Solid Cancers  

This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.

The Evolution of Fetal Surgery

Fetal surgery is the newest surgical specialty with a compelling history. The development of fetal surgery began in primates and lambs and, in its most basic form, was first performed in humans in 1965. Since its introduction, the field has expanded and changed dramatically. Several of these changes have involved the ethical aspect of fetal surgery. This field conflicts with the Hippocratic oath mantra of “first do no harm” as one of the patients, the mother, receives no benefit from these procedures. The ethical dilemma resulted in stringent inclusion and exclusion criteria for fetal operations. Initially, fetal surgery was only indicated for life-threatening conditions of the fetus but is now offered in some disease processes to improve quality of life for the child. As the field has matured, it has grown to encompass numerous different types of fetal interventions. Similar to other areas of surgery, the trend has been to migrate from more invasive to less invasive procedures. Currently, some of these therapies are performed entirely percutaneously. Theoretically, this trend would improve outcomes for both the mother and fetus. While this has generally proven true, there are some important exceptions to this rule. Finally, as the field continues to evolve, much research is being performed looking at possible new types of fetal interventions. Some of these procedures, such as fetal stem cell therapy and fetal gene therapy, could change the face of modern medicine.

A Role for in Vitro Disease Models in the Landscape of Preclinical Cardiotoxicity and Safety Testing

Drug-induced cardiotoxicity is one of the predominant reasons for drug attrition and withdrawals. This is of critical concern when potentially cardiotoxic drugs are administered to individuals with inherited arrhythmogenic cardiac diseases or with metabolic diseases such as obesity and diabetes, which are key risk factors for cardiovascular diseases. Pathophysiological alteration prevalent under such conditions can alter or exacerbate cardiotoxic responses. The growing incidence of obesity, diabetes and metabolic syndrome subject a significant percentage of the population to drug treatments, thereby augmenting their risk for drug-induced cardiovascular toxicity. Hence, screening for drug-induced cardiotoxicity early in the preclinical stages of drug development, by using appropriate human disease models, can be effective in ensuring safety in clinical trials and preventing late stage and post-marketing drug withdrawals owing to cardiotoxicity. The advent of human pluripotent stem cells (hPSC) and induced pluripotent stem cell (iPSC)-derived cardiomyocytes are revolutionizing safety/toxicity screening in human cells by providing relevant human-specific, renewable model systems to explore human drug toxicity. The ability to generate patient-specific iPSCs that can model cardiac diseases, now offers a valuable option that can further improve drug safety assessments and enable a more accurate prediction of toxicity that occurs in the representative population that are prescribed the drugs. Use of appropriate disease models will not only provide cost savings by decreasing potential drug attrition and withdrawals, seen with many drugs, but will also be a promising option to advance precision medicine

Calcium Transient Assays for Compound Screening with Human iPSC-derived Cardiomyocytes: Evaluating New Tools

Calcium (Ca2+) plays a central role in regulating many biological processes in the cell from muscle contraction to neurotransmitter release. The need for reliable fluorescent calcium indicator dyes is of vast importance for studying many aspects of cell biology as well as screening compounds using phenotypic high throughput assays. We have assessed two of the latest generation of calcium indicator dyes, FLIPR Calcium 6 and Cal-520 AM for studying calcium transients (CaTs) in induced pluripotent stem cell (iPSC) -derived human cardiomyocytes. FLIPR Calcium 6 and Cal-520 dyes both displayed robust CaTs with a high signal-to-noise ratio (SNR) and were non-toxic to the cells. The analysis showed that CaT amplitudes were stable between measurements, but CaT duration was more variable and tended to increase between reads. Two methods were compared for drug-screening hit-selection; difference in average (unstandardized) and standardized difference. The unstandardized difference was better for assessing CaT amplitude, whereas standardized difference was equal to or better for assessing CaT duration. In summary, FLIPR Calcium 6 and Cal-520 are suitable dyes for drug-screening using iPSC-derived human cardiomyocytes.

MicroRNA-1285 Might Potentially Regulate OCT4 Gene Expression by Direct Targeting of its Promoter

The human OCT4 gene encodes a transcription factor that maintains pluripotency and self-renewal in Embryonic Stem (ES) cells. This gene generates several known transcripts by alternative promoter and alternative splicing (OCT4A, OCT4B and OCT4B1). Even though OCT4A is the main isoform responsible for stemness properties, several recent controversial studies claimed that this isoform is expressed in cancer cell lines and differentiated cells, in addition to the ES cells. Our in silico studies revealed that OCT4A promoter has a completely match binding site for hsa-miR-1285. This microRNA was detected in the human embryonic stem cells for the first time and further studies showed that miR-1285 can target some tumor suppressor genes,(TSGs), such as p53, and oncogenic genes, such as TGM2. Additional bioinformatics analysis of short RNA sequencing data from ENCODE cell lines showed that miR-1285 is expressed in different cancer cell lines and differentiated cells. In this study, we supposed that miR-1285 potentially can bind to the OCT4 promoter and might regulate transcription of the OCT4 in the human cancer cell lines and differentiated cells.

Molecular Cytogenetic Investigations in a Novel Chromosomal Abnormality of t(10;15)(q22;q22) in a Pediatric Precursor-B-Acute Lymphoblastic Leukemia Patient

Acute lymphoblastic leukemia (ALL) is a rapid form of leukemia characterized by clonal proliferation and accumulation of immature hematopoietic stem cells of the lymphoid lineage in the bone marrow as well as peripheral blood. Chromosomal aberrations identified in childhood ALL have an important role in disease diagnosis, prognosis and management. We present the results of hematologic, immunophenotypic, cytogenetic, FISH and Multiplex RT-PCR analysis of a 6-year-old boy diagnosed with B-cell precursor Acute Lymphoblastic Leukemia (BCP- ALL). In this study, we identified a novel chromosomal translocation t(10;15)(q22;q22) by cytogenetic and FISH analysis. To the best of our knowledge, this is the first report of this novel chromosomal translocation in this subset of ALL and has not yet been reported elsewhere. This rearrangement may include certain cancer associated tumor suppressor gene(s) or genes involved in apoptosis and transcription regulation, which on loss of normal function may lead to leukaemogenesis.