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Best matches for Stem Cell Differentiation.pdf:

Pluripotent Stem Cells in Adult Tissues: Struggling To Be Acknowledged Over Two Decades. Bhartiya D et al. Stem Cell Rev. (2017)

Stem cells and the evolving notion of cellular identity. Daley GQ et al. Philos Trans R Soc Lond B Biol Sci. (2015)

Adult stem cells: hopes and hypes of regenerative medicine. Dulak J et al. Acta Biochim Pol. (2015)

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1.
Int J Hematol. 2019 Mar 16. doi: 10.1007/s12185-019-02628-8. [Epub ahead of print]

Pre- and post-transplant ponatinib for a patient with acute megakaryoblastic blast phase chronic myeloid leukemia with T315I mutation who underwent allogeneic hematopoietic stem cell transplantation.

Author information

1
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan.
2
Department of Hematology, Kainan Hospital, Yatomi, Japan.
3
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan. skusumot@med.nagoya-cu.ac.jp.

Abstract

A 42-year-old female complaining of fever and night sweats was diagnosed with acute megakaryoblastic blast phase chronic myeloid leukemia (CML-BP). She had massive splenomegaly, left pleural effusion with leukemia infiltration, and moderate myelofibrosis. She received dasatinib monotherapy (140 mg/day) as for induction, after which her pleural effusion rapidly resolved and hematological remission was achieved. However, CML relapsed 4 months after starting dasatinib due to increased BCR-ABL fusion signals in the peripheral blood. The T315I mutation was also detected at the recurrence of CML. As a salvage treatment, ponatinib monotherapy (45 mg/day) was started immediately. After 5 months, BCR-ABL fusion signals decreased to 5%, and myelofibrosis improved from MF Grade 2 to 1; she then underwent allogeneic bone marrow transplantation from an unrelated donor. However, the graft failed, and cord blood transplantation (CBT) was performed. Ponatinib (15 mg/day) was continued after CBT as a maintenance treatment, with molecular complete response continuing for more than 1 year with no severe adverse events, including cardiovascular events. There is limited evidence regarding the optimal dose and schedule of ponatinib before and after allogeneic hematopoietic stem cell transplantation, especially in patients with CML-BP having T315I mutation; thus, well-designed clinical trials are warranted.

KEYWORDS:

Allogeneic bone marrow transplantation; Chronic myeloid leukemia; Cord blood transplantation; Megakaryoblastic blast phase; Ponatinib

2.
Differentiation. 2019 Mar 8;106:49-56. doi: 10.1016/j.diff.2019.03.001. [Epub ahead of print]

The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease.

Author information

1
Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain.
2
Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain; Aragon's Health Science Research Institute (IACS), Zaragoza, Spain.
3
Aragon's Health Science Research Institute (IACS), Zaragoza, Spain.
4
Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain; Health Research Institute of Jiménez Díaz Foundation (IIS FJD), Madrid, Spain; Biomedical and Aerospace Engineering Department, University Carlos III of Madrid, Spain.
5
Pathology Department, University Hospital Lozano Blesa, Zaragoza, Spain.
6
Health Research Institute of Aragón (IIS Aragón), Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Health Research Institute of Jiménez Díaz Foundation (IIS FJD), Madrid, Spain; Biomedical and Aerospace Engineering Department, University Carlos III of Madrid, Spain. Electronic address: pmbaptista@iisaragon.es.

Abstract

The liver stem cell niche is a specialized and dynamic microenvironment with biomechanical and biochemical characteristics that regulate stem cell behavior. This is feasible due to the coordination of a complex network of secreted factors, small molecules, neural, blood inputs and extracellular matrix (ECM) components involved in the regulation of stem cell fate (self-renewal, survival, and differentiation into more mature phenotypes like hepatocytes and cholangiocytes). In this review, we describe and summarize all the major components that play essential roles in the liver stem cell niche, in particular, growth factor signaling and the biomechanical properties of the ECM.

KEYWORDS:

ECM; Growth factors; Liver development; Mechanobiology; Progenitor cell; Stem cell; Stem cell niche

Publication type

Publication type

3.
Differentiation. 2019 Mar 2;106:42-48. doi: 10.1016/j.diff.2019.02.006. [Epub ahead of print]

The role of cellular interactions in the induction of hepatocyte polarity and functional maturation in stem cell-derived hepatic cells.

Author information

1
Department of Surgery, Keck School of Medicine, University of Southern California, USA.
2
Department of Surgery, Keck School of Medicine, University of Southern California, USA. Electronic address: toshiomi@usc.edu.

Abstract

The unique microenvironment found within the liver in vivo plays a key role in the induction of functional maturation in the developing hepatocyte. During organogenesis, hepatocytes acquire a polar phenotype that allows them to perform their functions of bile production and transport, protein synthesis, metabolism, and detoxification simultaneously, independently, and efficiently. It is thought that the induction of polarity and functional maturation in hepatocytes is dependent on the complex interplay of cell-cell and cell-extracellular matrix (ECM) interactions. While this process is highly efficient in the human liver, it has been shown that hepatocytes rapidly lose their functions when placed in cell culture. This poses a challenge for the development of a bioartificial liver (BAL) support system, which utilizes a live cellular source to perform hepatic functions in the event of acute liver failure or primary nonfunction. However, once the molecular mechanisms underlying the induction of hepatocyte polarity are fully identified, it will be possible to develop highly functional hepatic cells from human pluripotent stem cells (hPSCs). This new cell line would be an ideal cellular source for a BAL system, as it would have both the functionality and longevity to support a patient through the entire clinical course of treatment. In this review, we explore the literature that has examined the potential mechanisms that induce polarity in the developing hepatocyte and discuss the future implications of this knowledge in a clinical setting from a bioengineering perspective.

KEYWORDS:

Bioartificial liver; Cell culture; Cell differentiation; Cell physiology; Hepatocytes; Pluripotent stem cells

Publication type

Publication type

4.
Biol Blood Marrow Transplant. 2019 Mar 13. pii: S1083-8791(19)30187-9. doi: 10.1016/j.bbmt.2019.03.012. [Epub ahead of print]

Screening for family psychosocial risk in pediatric hematopoietic stem cell transplantation with The Psychosocial Assessment Tool (PAT).

Author information

1
Cincinnati Children's Hospital Medical Center; University of Cincinnati College of Medicine.
2
University of Alabama at Birmingham; Children's of Alabama.
3
Nemours Children's Health System; Sidney Kimmel Medical School at Thomas Jefferson University.
4
Perelman School of Medicine of the University of Pennsylvania.
5
Nemours Children's Health System.
6
University of Pennsylvania School of Nursing.
7
Nemours Children's Health System; Sidney Kimmel Medical School at Thomas Jefferson University. Electronic address: anne.kazak@nemours.org.

Abstract

OBJECTIVE:

Family psychosocial risk screening is an important initial step in delivering evidence-based care in hematopoietic stem cell transplantation (HCT). Establishing an evidence-based screening approach that is acceptable, reliable and valid is an essential step in psychosocial care delivery.

METHODS:

This is a three-institution multi-method study. In Part 1 caregivers of children about to undergo HCT (n = 140) completed the Psychosocial Assessment Tool (PAT), a brief parent report screener adapted for HCT, and validating questionnaires. Families received feedback on their risks identified on the PAT. In Part 2, 12 caregivers completed a semi-structured interview about their perceptions of the PAT and the feedback process. The reliability and validity of the PAT-HCT total and subscales scores were tested using Kuder-Richardson-20 (KR-20) and Pearson correlations. Thematic content analysis was used to analyze the qualitative interview data.

RESULTS:

Internal consistency for the total score (KR-20 = 0.88) and the Child Problems, Sibling Problems, Family Problems and Stress Reactions subscales were strong (KR-20 > 0.70). Family Structure, Social Support and Family Beliefs subscales were adequate (KR-20 = 0.55 - 0.63). Moderate to strong correlations with the criteria measures provided validation for the total and subscale scores. Feedback was provided to 97.14% of the families who completed the PAT-HCT and mean ratings of acceptability were above 4.00 (5-point scale). The qualitative data indicate that families appreciate the efforts to provide screening and feedback.

CONCLUSIONS:

The PAT-HCT is a psychometrically sound screener for use in HCT. Feedback can be given to families. Both the screener and the feedback process are acceptable to caregivers.

KEYWORDS:

Families; HCT; Healthcare delivery; Pediatrics; Psychosocial; Psychosocial Assessment Tool (PAT); Risk screening

5.
Biol Blood Marrow Transplant. 2019 Mar 13. pii: S1083-8791(19)30185-5. doi: 10.1016/j.bbmt.2019.03.010. [Epub ahead of print]

Protecting the selfless:towards more comprehensive care for pediatric related stem cell donors.

Author information

1
Dana-Farber/Children's Hospital Boston, 44 Binney Street, Boston, MA.

Abstract

None.

6.
Biol Blood Marrow Transplant. 2019 Mar 13. pii: S1083-8791(19)30189-2. doi: 10.1016/j.bbmt.2019.03.014. [Epub ahead of print]

A tale of two eras: the story of autologous stem cell transplantation with and without thiotepa for primary central nervous system lymphoma.

Author information

1
Department of Malignant Hematology, Levine Cancer Institute/Atrium Health, Charlotte, NC. Electronic address: bei.hu@atriumhealth.org.
7.
Acta Biomater. 2019 Mar 13. pii: S1742-7061(19)30187-4. doi: 10.1016/j.actbio.2019.03.021. [Epub ahead of print]

Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration.

Author information

1
Faculty of Dentistry, National University of Singapore, Singapore.
2
Institute of Medical Biology, Agency for Science, Technology and Research, Singapore.
3
Institute of Medical Biology, Agency for Science, Technology and Research, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4
Faculty of Dentistry, National University of Singapore, Singapore; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore. Electronic address: dentohws@nus.edu.sg.

Abstract

Mesenchymal stem cells (MSCs) are potential therapeutics for the treatment of periodontal defects. It is increasingly accepted that MSCs mediate tissue repair through secretion of trophic factors, particularly exosomes. Here, we investigated the therapeutic effects of human MSC exosome-loaded collagen sponge for regeneration of surgically created periodontal intrabony defects in an immunocompetent rat model. We observed that relative to control rats, exosome-treated rats repaired the defects more efficiently with regeneration of periodontal tissues including newly-formed bone and periodontal ligament (PDL). We also observed that concomitant with this, there was increased cellular infiltration and proliferation. We therefore postulated that MSC exosomes enhanced regeneration through increased cellular mobilisation and proliferation. Using PDL cell cultures, we demonstrated that MSC exosomes could increase PDL cell migration and proliferation through CD73-mediated adenosine receptor activation of pro-survival AKT and ERK signalling. Inhibition of AKT or ERK phosphorylation suppressed PDL cell migration and proliferation. Our findings demonstrated for the first time that MSC exosomes enhance periodontal regeneration possibly by increasing PDL migration and proliferation. This study suggests that MSC exosome is a viable ready-to-use and cell-free MSC therapeutic for the treatment of periodontal defects. STATEMENT OF SIGNIFICANCE: Mesenchymal stem cell (MSC) therapies have demonstrated regenerative potential for the treatment of periodontal defects. However, translation of cellular therapies is hampered by challenges in maintaining optimal cell vitality and viability from manufacturing and storage to final delivery to patients. Although the use of MSCs for tissue repair was first predicated on their differentiation potential, the therapeutic efficacy of MSCs has increasingly been attributed to its paracrine secretion, particularly exosomes or small extracellular vesicles. In this study, MSC exosome-loaded collagen sponge enhanced periodontal regeneration in an immunocompetent rat periodontal defect model without any obvious adverse effects. These findings provide the basis for future development of MSC exosomes as a cell-free strategy for periodontal regeneration.

KEYWORDS:

Bone; Exosomes; Mesenchymal stem cells; Periodontal ligament; Regeneration

8.
Clin Lymphoma Myeloma Leuk. 2019 Jan 3. pii: S2152-2650(18)31189-3. doi: 10.1016/j.clml.2018.12.022. [Epub ahead of print]

Immune Signatures Associated With Clonal Isotype Switch After Autologous Stem Cell Transplantation for Multiple Myeloma.

Author information

1
Department of Medicine, New York University School of Medicine, New York, NY.
2
Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH.
3
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.
4
Division of Hematology and Oncology, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH.
5
Adult Hematologic Malignancies and Stem Cell Transplant Program, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH.
6
Myeloma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
7
Division of Hematology and Oncology, University Hospital Cleveland Medical Center, Cleveland, OH.
8
Case Western Reserve University School of Medicine, Cleveland, OH.
9
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
10
Adult Hematologic Malignancies and Stem Cell Transplant Program, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH; Case Western Reserve University School of Medicine, Cleveland, OH.
11
Adult Hematologic Malignancies and Stem Cell Transplant Program, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH; Case Western Reserve University School of Medicine, Cleveland, OH. Electronic address: exm301@case.edu.

Abstract

BACKGROUND:

High-dose chemotherapy and autologous stem cell transplantation (ASCT) are integral components of the overall treatment for patients with multiple myeloma (MM) aged ≤ 65 years. The emergence of oligoclonal immunoglobulin bands (ie, immunoglobulins differing from those originally identified at diagnosis [termed clonal isotype switch (CIS)]) has been reported in patients with MM after high-dose chemotherapy followed by autologous stem cell transplantation. However, the clinical relevance and the correlation with immune reconstitution remains unclear.

PATIENTS AND METHODS:

Patients with MM who had undergone ASCT from 2007 to 2016 were included in the present study. The percentage of natural killer cells, B-cells, and T-cells was measured using flow cytometry in pre- and post-ASCT bone marrow samples. CIS was defined as the appearance of a new serum monoclonal spike on serum protein electrophoresis and immunofixation that differed from original heavy or light chain detected at diagnosis.

RESULTS:

A retrospective analysis of 177 patients with MM who had undergone ASCT detected CIS in 39 (22%). CIS after ASCT correlated with improved progression-free survival (52.2 vs. 36.6 months; P = .21) and overall survival (75.1 vs. 65.4 months; P = .021). Patients with a relapse had an isotype that differed from a CIS, confirming the benign nature of this phenomenon. CIS was also associated with lower CD8 T-cell percentages and a greater CD4/CD8 ratio (2.8 vs. 0.2; P = .001) compared with patients who did not demonstrate a CIS, suggestive of more profound T-cell immune reconstitution in this group.

CONCLUSION:

Taken together, our data have demonstrated that a CIS is a benign phenomenon and correlates with a reduced disease burden and enriched immune repertoire beyond the B-cell compartment.

KEYWORDS:

Autologous stem cell transplantation; Clonal isotype switch; Immune reconstitution; Multiple myeloma; Myeloma microenvironment

9.
Stem Cell Res. 2019 Mar 6;36:101416. doi: 10.1016/j.scr.2019.101416. [Epub ahead of print]

Generation of the human induced pluripotent stem cell (hiPSC) line PSMi007-A from a Long QT Syndrome type 1 patient carrier of two common variants in the NOS1AP gene.

Author information

1
Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
2
Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Molecular Medicine, Unit of Cardiology, Università degli studi di Pavia, Pavia, Italy.
3
Department of Molecular Medicine, Unit of Genetics, Università degli studi di Pavia, Pavia, Italy.; Neurogenetics Unit, Fondazione IRCCS Santa Lucia, Rome, Italy.
4
Laboratory of Oncohaematological Cytogenetic and Molecular Diagnostics, Division of Haematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
5
Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.; Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy.; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
6
Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy.
7
Department of Internal Medicine, University of Stellenbosch, Tygerberg, South Africa.
8
Coronary Care Unit and Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; Department of Molecular Medicine, Unit of Cardiology, Università degli studi di Pavia, Pavia, Italy.; Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: m.gnecchi@unipv.it.

Abstract

We generated human induced pluripotent stem cells (hiPSCs) from a symptomatic Long QT Syndrome (LQTS) type 1 patient, belonging to a South African (SA) founder population segregating the heterozygous mutation c.1022C > T p.A341V on the KCNQ1 gene. The patient is also homozygous for the two minor variants rs4657139 and rs16847548 on the NOS1AP gene, associated with greater risk for cardiac arrest and sudden death in LQTS mutation carriers of the founder population. hiPSCs, obtained using four retroviruses encoding the reprogramming factors OCT4, SOX2, cMYC and KLF4, display pluripotent stem cell characteristics, and can be differentiated into spontaneously beating cardiomyocytes (hiPSC-CMs).

10.
Drug Resist Updat. 2019 Mar 8;42:35-45. doi: 10.1016/j.drup.2018.03.003. [Epub ahead of print]

Glioblastoma cancer stem cell biology: Potential theranostic targets.

Author information

1
Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
2
Department of Human Anatomy & Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
3
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
4
Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran.
5
Heart Rhythm Program, Southlake Regional Health Centre, Toronto ON, Canada.
6
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Immunology, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
7
Department of Molecular Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland; Centre de biophysique moléculaire, UPR4301 CNRS CS80054, Rue Charles Sadron, 45071 Orleans cedex 2, France; LinkoCare Life Sciences AB, 583 30, Linköping, Sweden.
8
Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
9
Department of Neurosurgery, Kashan University of Medical Sciences, Kashan, Iran.
10
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address: mebrahimi@royaninstitute.org.
11
Pediatric Stem Cell Transplant Department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aahamidieh@tums.ac.ir.

Abstract

Glioblastoma multiforme (GBM) is among the most incurable cancers. GBMs survival rate has not markedly improved, despite new radical surgery protocols, the introduction of new anticancer drugs, new treatment protocols, and advances in radiation techniques. The low efficacy of therapy, and short interval between remission and recurrence, could be attributed to the resistance of a small fraction of tumorigenic cells to treatment. The existence and importance of cancer stem cells (CSCs) is perceived by some as controversial. Experimental evidences suggest that the presence of therapy-resistant glioblastoma stem cells (GSCs) could explain tumor recurrence and metastasis. Some scientists, including most of the authors of this review, believe that GSCs are the driving force behind GBM relapses, whereas others however, question the existence of GSCs. Evidence has accumulated indicating that non-tumorigenic cancer cells with high heterogeneity, could undergo reprogramming and become GSCs. Hence, targeting GSCs as the "root cells" initiating malignancy has been proposed to eradicate this devastating disease. Most standard treatments fail to completely eradicate GSCs, which can then cause the recurrence of the disease. To effectively target GSCs, a comprehensive understanding of the biology of GSCs as well as the mechanisms by which these cells survive during treatment and develop into new tumor, is urgently needed. Herein, we provide an overview of the molecular features of GSCs, and elaborate how to facilitate their detection and efficient targeting for therapeutic interventions. We also discuss GBM classifications based on the molecular stem cell subtypes with a focus on potential therapeutic approaches.

KEYWORDS:

Cancer stem cell; Chemoresistance; Glioblastoma; Notch; Self-renewal; Wnt

11.
Eur J Pharmacol. 2019 Mar 12. pii: S0014-2999(19)30167-0. doi: 10.1016/j.ejphar.2019.03.012. [Epub ahead of print]

Protective effect of [Pyr1]-apelin-13 on oxidative stress-induced apoptosis in hair cell -like cells derived from bone marrow mesenchymal stem cells.

Author information

1
Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: niknazar.somayeh@gmail.com.
2
Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Anatomical Sciences and Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3
Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4
Skull Base Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5
Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: dr_khoshsirat@yahoo.com.
6
Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: aapeyvandi2@gmail.com.

Abstract

Oxidative stress plays an important role in auditory dysfunction. Exogenous cell therapy has brought new hopes for repairing mammalian inner ear hair cells. However, poor cell viability of transplanted cells under oxidative stress conditions has limited their therapeutic potential. The adipocytokine apelin-13 was isolated from a bovine stomach. Apelin-13 might protect oxidative stress-induced hair cell damage was raised considering other oxidative stress-induced injury, including brain ischemia-induced cell death. Therefore, we evaluated the protective effects of apelin- 13 on the damage induced by hydrogen peroxide (H2O2) to the hair cells-derived from bone marrow mesenchymal stem cells (BMSCs) in vitro. Stem cells were differentiated into hair cell- like cells with B27, FGF, EGF and IGF-1. Expression of neuron specific markers including β tubulin III, Nestin, MAP2, Neurofilament 68 and GFAP was tested by flow cytometry. As well, inner ear hair cell markers such as Myosin VIIA, Sox2 and TrkB expression were assayed by immunocytochemistry (ICC) method. We designed an in vitro model of oxidative stress by exposing hair cell- like cells to H2O2. Protein expression levels of caspase-3, Bax and Bcl-2 were detected by western blot. Apoptotic cells were also detected by acridin-orange staining and TUNEL assay. Protein expression of caspase-3 and Bax/Bcl-2 ratio was significantly lower in the apelin-13-pretreated group than only H2O2 treated group. In addition, apoptotic cells were significantly decreased in the apelin-13+H2O2 co-treated cells compared to the H2O2-treated group. Treating hair cells-like cells with apelin13 increases their survival against oxidative stress damage by inhibition of apoptosis signaling pathway.

KEYWORDS:

Apelin-13; Apoptosis; Bcl-2/Bax ratio; Caspase-3; Hair Cell; Oxidative Stress

12.
Biochimie. 2019 Mar 12. pii: S0300-9084(19)30069-0. doi: 10.1016/j.biochi.2019.03.002. [Epub ahead of print]

Impact of proteolysis on cancer stem cell functions.

Author information

1
Institute of Molecular Medicine and Cell Research, Medical Faculty, University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Freiburg, Germany.
2
Institute of Molecular Medicine and Cell Research, Medical Faculty, University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Freiburg, Germany; German Cancer Consortium (DKTK) partner site Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany; Comprehensive Cancer Center Freiburg, Freiburg, Germany. Electronic address: thomas.reinheckel@mol-med.uni-freiburg.de.

Abstract

Cancer cells within a tumor are heterogeneous and exist in a variety of functionally distinct cell states, which are thought to be hierarchically organized. The cell on top of this hierarchy, the cancer stem cell (CSC) or, alternatively, tumor initiating cell (TIC), is responsible for initiation, maintenance, progression, and relapse of tumors. For the execution of these functions, CSC are equipped with distinct molecular tools. Although proteolytic enzymes in cancers have been extensively studied in general, relatively few studies have addressed proteases in function and fate of CSC/TICs. Here we review protease involvement in cell biological hallmarks of CSC/TICs such as cellular self-renewal, extracellular matrix remodeling and cell motility, resistance to radio- and chemotherapies, as well as evasion of the immune system. In general, CSC/TICs are characterized by a comparatively high expression and activity of proteases. It appears that CSC/TICs install a high degree of pericellular proteolysis depending on metalloproteases such as ADAMs and MMPs but also on secreted serine- and cysteine proteases. Interestingly, it turned out that not all proteases promote the malignant behavior of CSC/TICs. In fact, some proteases, such as ADAM 23, cathepsin K, and granzyme B, have been shown to negatively regulate CSC/TIC functions, thereby exhibiting anti-tumor effects. Finally, we discuss how the enhanced proteolytic signature of CSC/TICs can be used for their therapeutic targeting in order to render this clinically decisive subpopulation of cancer cells harmless.

KEYWORDS:

Carcinoma; Metalloproteases; Proteases; Tumor initiating cells

Publication type

Publication type

13.
Biol Blood Marrow Transplant. 2019 Mar 12. pii: S1083-8791(19)30154-5. doi: 10.1016/j.bbmt.2019.03.003. [Epub ahead of print]

Changes in immunosuppressive treatment of chronic graft-versus-host disease - comparison of 2 surveys within allogeneic hematopoietic stem cell transplant centers in Germany, Austria and Switzerland.

Author information

1
Dept. of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany. Electronic address: daniel.wolff@ukr.de.
2
Universitätsklinikum Jena, Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Jena, Germany.
3
3rd Medical Dept., Hematology, Oncology and Pneumology, University Medical Center Mainz, Germany.
4
Medizinische Klinik 2, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany.
5
Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
6
Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Freiburg, Germany.
7
Klinikum Nuernberg, Dept. of Internal Medicine V, Nuernberg, Germany.
8
Dept. of Hematology, Oncology and Tumorimmunology, Campus Virchow Klinikum, Charite, Berlin, Germany.
9
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
10
III. Medizinische Klinik Hämatologie und Onkologie Universitätsmedizin Mannheim, Mannheim, Germany.
11
Dept. of Internal Medicine I, University Hospital Dresden, Dresden, Germany.
12
St. Anna Children's Hospital, Medical University Vienna, Austria.
13
Dept. of Hematology, University Hospital Erlangen, Germany.
14
Dept. of Hematology, University Hospital Basel, Switzerland.
15
Dept. of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
16
Dept. of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Germany.
17
Dept. of Hematology, University Hospital Muenster, Germany.
18
Dept. for Bone Marrow Transplantation, University of Essen, Germany.
19
Division of Hematology, Dept. of Internal Medicine I, Medical University of Graz, Austria.

Abstract

Chronic graft-versus-host disease (cGvHD) remains the leading cause of late morbidity and mortality. Despite the growing number of treatment options in cGvHD evidence remains sparse. The German-Austrian-Swiss GvHD Consortium performed a survey on clinical practice in treatment of cGvHD among transplant centers in Germany, Austria and Switzerland in 2009 and 2018 and compared the results. The survey performed in 2009 contained 20 questions on 1st line treatment and related issues and 4 questions on 2nd line scenarios followed by a survey on all systemic and topic treatment options known and applied with 31/36 (86%) transplant centers responding. The survey in 2018 repeated 7 questions on 1st line treatment and 3 questions on 2nd line scenarios followed by an updated survey on all current systemic treatment options known and applied with 29/66 (43%) centers responding. In summary, the results show a large overlap of 1st line treatment practice in between centers and the 2 surveys, due to the lack of new data changing practice except significant heterogeneity of treatment of progressive onset type of cGvHD which can be explained by the lack of trials focusing on this high risk entity. In contrast, treatment options applied for 2nd line therapy vary considerably with new agents like ibrutinib and ruxolitinib entering clinical practice. Moreover, treatment of bronchiolitis obliterans syndrome demonstrates heterogeneity in applied therapeutic options and sequence due to the lack of controlled data and different conclusions from already existing evidence. In summary, the surveys results demonstrate an increasing number of treatment options applied in cGvHD accompanied by a significant heterogeneity in 2nd line treatment and underline the urgent need for clinical trials and registry analyses on rare entities with high mortality like progressive onset type and lung involvement of cGvHD.

KEYWORDS:

Allogeneic hematopoietic stem cell transplantation; Bone marrow transplantation; Chronic graft-versus-host disease; Immunosuppressive therapy

14.
Exp Hematol. 2019 Mar 12. pii: S0301-472X(19)30128-6. doi: 10.1016/j.exphem.2019.03.001. [Epub ahead of print]

KLF1 Mutation E325K Induces Cell-cycle Arrest in Erythroid Cells Differentiated from Congenital Dyserythropoietic Anemia (CDA) Patient-specific Induced Pluripotent Stem Cells.

Author information

1
Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
2
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
3
Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
4
Japanese Red Cross Chiba Blood Center.
5
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
6
Department of Research and Development, Central Blood Institute, Japanese Red Cross Society, Tokyo, Japan.
7
Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan.
8
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
9
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
10
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
11
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan. Electronic address: kanno.hitoshi@twmu.ac.jp.
12
Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Department of Advanced Molecular and Cell Therapy, Kyushu University Hospital, Fukuoka, Japan. Electronic address: k-tani@ims.u-tokyo.ac.jp.

Abstract

Krüppel-like factor 1 (KLF1), a transcription factor controlling definitive erythropoiesis, is involved in sequential control of terminal cell division and enucleation via fine regulation of key cell-cycle regulator genes expression in erythroid lineage cells. Type IV congenital dyserythropoietic anemia (CDA) is caused by a monoallelic mutation at the second zinc finger of KLF1 (c.973G>A; p.E325K). We recently diagnosed a female patient with type IV CDA with the identical missense mutation. To understand the mechanism underlying the dyserythropoiesis caused by the mutation, we generated induced pluripotent stem cells (iPSCs) from the CDA patient (CDA-iPSCs). The erythroid cells differentiated from CDA-iPSCs (CDA-erythroid cells) displayed multinucleated morphology, absence of CD44, and dysregulation of the KLF1 target gene expression. In addition, uptake of BrdU by CDA-erythroid cells was significantly decreased at the CD235a+/CD71+ stage, and microarray analysis revealed that cell-cycle regulator genes were dysregulated, including an increased expression of negative regulators such as CDKN2C and CDKN2A. Furthermore, inducible expression of the KLF1 E325K but not the wild-type KLF1 caused a cell cycle arrest at the G1 phase in CDA-erythroid cells. Microarray analysis of CDA-erythroid cells and real-time PCR analysis of the KLF1 E325K inducible expression system alsoshowed altered expression of several KLF1 target genes including erythrocyte membrane protein band 4.1 (EPB41), EPB42, glutathione-disulfide reductase (GSR), glucose phosphate isomerase (GPI), and ATPase phospholipid transporting8A1 (ATP8A1). Our data show that the E325K mutation in KLF1 is associated with disruption of transcriptional control of cell-cycle regulators in association with erythroid membrane/enzyme abnormalities, leading to dyserythropoiesis.

KEYWORDS:

Cell-Cycle; Congenital Dyserythropoietic Anemia; Induced Pluripotent Stem Cells; KLF1

15.
Cytotherapy. 2019 Mar 12. pii: S1465-3249(19)30028-3. doi: 10.1016/j.jcyt.2019.02.007. [Epub ahead of print]

Pleiotropic roles of autophagy in stem cell-based therapies.

Author information

1
NSU Cell Therapy Institute, Nova Southeastern University, Fort Lauderdale, Florida, USA. Electronic address: vbeljanski@nova.edu.
2
Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery and Anesthesiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Surgical Sciences, Division of Cardiothoracic Surgery and Anesthesiology, Uppsala University, Akademiska University Hospital, Uppsala, Sweden.
3
Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery and Anesthesiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Stem cells (SCs) have been proven to possess regenerative and immunomodulatory properties and can be used to treat diseases that involve loss of cells due to tissue damage or inflammation. For this approach to succeed, SCs or their derivatives should be able to engraft in the target tissue at least for a short period of time. Unfortunately, once injected, therapeutic SCs will encounter a hostile environment, including hypoxia, lack of nutrients and stromal support, and cells may also be targeted and rejected by the immune system. Therefore, SC's stress-response mechanisms likely play a significant role in survival of injected cells and possibly contribute to their therapeutic efficacy. Autphagy, a stress-response pathway, is involved in many different cellular processes, such as survival during hypoxia and nutrient deprivation, cellular differentiation and de-differentiation, and it can also contribute to their immunovisibility by regulating antigen presentation and cytokine secretion. Autophagy machinery interacts with many proteins and signaling pathways that regulate SC properties, including PI3K/Akt, mammalian target of rapamycin (mTOR), Wnt, Hedgehog and Notch, and it is also involved in regulating intracellular reactive oxygen species (ROS) levels. In this review, we contend that autophagy is an important therapeutic target that can be used to improve the outcome of SC-based tissue repair and regeneration. Further research should reveal whether inhibition or stimulation of autophagy increases the therapeutic utility of SCs and it should also identify appropriate therapeutic regimens that can be applied in the clinic.

Publication type

Publication type

16.
Cells. 2019 Mar 14;8(3). pii: E245. doi: 10.3390/cells8030245.

Hyaluronan-Based Hydrogel Scaffolds for Limbal Stem Cell Transplantation: A Review.

Yazdani M1, Shahdadfar A2, Jackson CJ3,4,5, Utheim TP6,7,8,9,10,11,12,13,14.

Author information

1
Department of Medical Biochemistry, Oslo University Hospital, Ullevål, 0450 Oslo, Norway. mazyar.yazdani.edu@gmail.com.
2
Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Ullevål, 0450 Oslo, Norway. aboulghassem.shahdadfar@medisin.uio.no.
3
Department of Medical Biochemistry, Oslo University Hospital, Ullevål, 0450 Oslo, Norway. catherinejoanjackson@gmail.com.
4
Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0450 Oslo, Norway. catherinejoanjackson@gmail.com.
5
Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0318 Oslo, Norway. catherinejoanjackson@gmail.com.
6
Department of Medical Biochemistry, Oslo University Hospital, Ullevål, 0450 Oslo, Norway. utheim2@gmail.com.
7
Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0450 Oslo, Norway. utheim2@gmail.com.
8
Institute of Oral Biology, Faculty of Dentistry, University of Oslo, 0318 Oslo, Norway. utheim2@gmail.com.
9
Department of Maxillofacial Surgery, Oslo University Hospital, 0450 Oslo, Norway. utheim2@gmail.com.
10
Department of Ophthalmology, Vestre Viken Hospital Trust, 3019 Drammen, Norway. utheim2@gmail.com.
11
Department of Ophthalmology, Stavanger University Hospital, 4011 Stavanger, Norway. utheim2@gmail.com.
12
Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5020 Bergen, Norway. utheim2@gmail.com.
13
Department of Ophthalmology, Sørlandet Hospital Arendal, 4604 Arendal, Norway. utheim2@gmail.com.
14
National Centre for Optics, Vision and Eye Care, Faculty of Health Sciences, University of South Eastern Norway, 3603 Kongsberg, Norway. utheim2@gmail.com.

Abstract

Hyaluronan (HA), also termed hyaluronic acid or hyaluronate, is a major component of the extracellular matrix. This non-sulfated glycosaminoglycan plays a key role in cell proliferation, growth, survival, polarization, and differentiation. The diverse biological roles of HA are linked to the combination of HA's physicochemical properties and HA-binding proteins. These unique characteristics have encouraged the application of HA-based hydrogel scaffolds for stem cell-based therapy, a successful method in the treatment of limbal stem cell deficiency (LSCD). This condition occurs following direct damage to limbal stem cells and/or changes in the limbal stem cell niche microenvironment due to intrinsic and extrinsic insults. This paper reviews the physical properties, synthesis, and degradation of HA. In addition, the interaction of HA with other extracellular matrix (ECM) components and receptor proteins are discussed. Finally, studies employing HA-based hydrogel scaffolds in the treatment of LSCD are reviewed.

KEYWORDS:

hyaluronan; hyaluronic acid; hydrogel scaffolds; limbal stem cell deficiency (LSCD); stem cell-based therapy; transplantation

PMID:
30875861
DOI:
10.3390/cells8030245
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Conflict of interest statement

The authors have no competing interests as defined by Cells journal, or other interests that might be perceived to influence the interpretation of the article.

17.
Nutrients. 2019 Mar 14;11(3). pii: E624. doi: 10.3390/nu11030624.

Baicalein Suppresses Stem Cell-Like Characteristics in Radio- and Chemoresistant MDA-MB-231 Human Breast Cancer Cells through Up-Regulation of IFIT2.

Koh SY1, Moon JY2, Unno T3,4, Cho SK5,6,7.

Author information

1
Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea. soyee.go@jejunu.ac.kr.
2
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea. owenmjy@jejunu.ac.kr.
3
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea. tatsu@jejunu.ac.kr.
4
Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea. tatsu@jejunu.ac.kr.
5
Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea. somikim@jejunu.ac.kr.
6
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea. somikim@jejunu.ac.kr.
7
Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea. somikim@jejunu.ac.kr.

Abstract

Resistance to both chemotherapy and radiation therapy is frequent in triple-negative breast cancer (TNBC) patients. We established treatment-resistant TNBC MDA-MB-231/IR cells by irradiating the parental MDA-MB-231 cells 25 times with 2 Gy irradiation and investigated the molecular mechanisms of acquired resistance. The resistant MDA-MB-231/IR cells were enhanced in migration, invasion, and stem cell-like characteristics. Pathway analysis by the Database for Annotation, Visualization and Integrated Discovery revealed that the NF-κB pathway, TNF signaling pathway, and Toll-like receptor pathway were enriched in MDA-MB-231/IR cells. Among 77 differentially expressed genes revealed by transcriptome analysis, 12 genes involved in drug and radiation resistance, including interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), were identified. We found that baicalein effectively reversed the expression of IFIT2, which is reported to be associated with metastasis, recurrence, and poor prognosis in TNBC patients. Baicalein sensitized radio- and chemoresistant cells and induced apoptosis, while suppressing stem cell-like characteristics, such as mammosphere formation, side population, expression of Oct3/4 and ABCG2, and CD44highCD24low population in MDA-MB-231/IR cells. These findings improve our understanding of the genes implicated in radio- and chemoresistance in breast cancer, and indicate that baicalein can serve as a sensitizer that overcomes treatment resistance.

KEYWORDS:

IFIT2; baicalein; cancer stem cell; chemoresistance; radioresistance; triple-negative breast cancer

PMID:
30875792
DOI:
10.3390/nu11030624
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18.
Cells. 2019 Mar 14;8(3). pii: E242. doi: 10.3390/cells8030242.

The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration.

Author information

1
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA. yyan73@wisc.edu.
2
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA. julie1.bejoy@famu.edu.
3
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA. mcm12g@my.fsu.edu.
4
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA. yli4@fsu.edu.

Abstract

The mechanism that causes the Alzheimer's disease (AD) pathologies, including amyloid plaque, neurofibrillary tangles, and neuron death, is not well understood due to the lack of robust study models for human brain. Three-dimensional organoid systems based on human pluripotent stem cells (hPSCs) have shown a promising potential to model neurodegenerative diseases, including AD. These systems, in combination with engineering tools, allow in vitro generation of brain-like tissues that recapitulate complex cell-cell and cell-extracellular matrix (ECM) interactions. Brain ECMs play important roles in neural differentiation, proliferation, neuronal network, and AD progression. In this contribution related to brain ECMs, recent advances in modeling AD pathology and progression based on hPSC-derived neural cells, tissues, and brain organoids were reviewed and summarized. In addition, the roles of ECMs in neural differentiation of hPSCs and the influences of heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and hyaluronic acid on the progression of neurodegeneration were discussed. The advantages that use stem cell-based organoids to study neural degeneration and to investigate the effects of ECM development on the disease progression were highlighted. The contents of this article are significant for understanding cell-matrix interactions in stem cell microenvironment for treating neural degeneration.

KEYWORDS:

extracellular matrix; neural degeneration; organoids; pluripotent stem cells; three-dimensional

PMID:
30875781
DOI:
10.3390/cells8030242
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19.
Stem Cell Res. 2019 Mar 7;36:101417. doi: 10.1016/j.scr.2019.101417. [Epub ahead of print]

Generation and characterization of a human induced pluripotent stem cell (iPSC) line (HEBHMUi001-A) from a sporadic Parkinson's disease patient.

Author information

1
Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Hebei Province 050017, China; Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Province 050017, China; Human Anatomy Department, Hebei Medical University, Hebei Province 050017, China.
2
Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Hebei Province 050017, China.
3
Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Hebei Province 050017, China; Second Affiliated Hospital of Hebei Medical University, China.
4
The Fourth Hospital of Shijiazhuang, China.
5
Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Hebei Province 050017, China; Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
6
Hebei Medical University-National University of Ireland Galway Stem Cell Research Center, Hebei Medical University, Hebei Province 050017, China; Hebei Research Center for Stem Cell Medical Translational Engineering, Hebei Province 050017, China; Human Anatomy Department, Hebei Medical University, Hebei Province 050017, China. Electronic address: Huixiancuihmu@163.com.

Abstract

We generated a human induced pluripotent stem cell (iPSC) line from the skin fibroblasts of a 62-year-old female patient clinically diagnosed with sporadic Parkinson's disease (PD). The generated iPSCs maintained their normal karyotype, expressed pluripotency stem cell markers, and were demonstrated to be capable of differentiating into cells representative of the three embryonic germ layers. The generated line could be used for PD modeling in order to understand the mechanisms that influence the disorder.

20.
Transpl Infect Dis. 2019 Mar 15:e13073. doi: 10.1111/tid.13073. [Epub ahead of print]

Low incidence of HHV-6 reactivation in haploidentical hematopoietic stem cell transplantation with corticosteroid as graft-versus-host disease prophylaxis compared with cord blood transplantation.

Author information

1
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
2
Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Abstract

BACKGROUND:

Human leukocyte antigen (HLA) mismatch and the administration of immunosuppressive agents are considered risks for human herpesvirus 6 (HHV-6) reactivation after stem cell transplantation (SCT). However, the incidence of HHV-6 reactivation in HLA-mismatched related SCT remains unknown.

METHODS:

We monitored plasma HHV-6 DNA loads weekly using real-time quantitative polymerase chain reaction for 5 weeks after SCT and compared serum IL-6 levels in HLA-mismatched SCT groups.

RESULTS:

Compared with detection in all 11 umbilical cord blood transplantation (CBT) patients (100%), plasma HHV-6 DNA was detected in only 3 of 42 haplo-SCT patients (7.1%) despite the use of methylprednisolone and antithymocyte globulin as graft-versus-host disease prophylaxis and a reduced-intensity conditioning regimen, respectively. Correspondingly, serum IL-6 levels in haplo-SCT patients were significantly lower than those in CBT patients. No HHV-6-associated encephalitis developed in either groups.

CONCLUSIONS:

Neither HLA disparity nor the use of methylprednisolone and antithymocyte globulin were risk factors for HHV-6 reactivation in our haplo-SCT patients. Rather than increasing risk, the administration of immunosuppressive agents potentially prevented HHV-6 reactivation after haplo-SCT by suppressing IL-6 production. This article is protected by copyright. All rights reserved.

KEYWORDS:

CBT ; HHV-6 reactivation; HLA-mismatched/haploidentical transplantation; encephalitis; interleukin-6

PMID:
30875143
DOI:
10.1111/tid.13073
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