Michael Pepper
University of Pretoria, Immunology, Faculty Member
- Michael Pepper is Director of the Institute for Cellular and Molecular Medicine, Director of the South African Medica... moreMichael Pepper is Director of the Institute for Cellular and Molecular Medicine, Director of the South African Medical Research Council Extramural Unit for Stem Cell Research and Therapy, and a Research Professor in the Department of Immunology in the Faculty of Health Sciences at the University of Pretoria. He is also professeur associé in the Department of Genetic Medicine and Development in the Faculty of Medicine at the University of Geneva, Switzerland.
Michael obtained his MBChB in 1982 from the Faculty of Medicine at the University of Cape Town, and moved to Geneva in 1986, where he obtained his PhD in 1990, MD in 1992 and Privat Docent in 1997. He returned to South Africa in July 2004. Michael maintains research and teaching commitments in Pretoria and Geneva.
Michael has worked extensively in the field of clinically-oriented (translational) molecular cell biology and has made seminal contributions to understanding the mechanisms of angiogenesis and lymphangiogenesis. His current scientific interests are in the fields of cell and gene therapy and the human genome as well as the ethical, legal and social implications (ELSI) of work in these fields.
Michael led a consensus study for the Academy of Science of South Africa entitled “Human Genetics and Genomics in South Africa: Ethical, Legal and Social Implicaions” which was launched in December 2018, and is currently leading a project on the ELSI of gene therapy (including gene editing) in South Africa. He has also been working with the Department of Health on legislation pertaining to Chapter 8 of the National Health Act and regulations thereto since mid-2009. Michael is immediate past-President and Chairman of the Board of the South African Tissue Bank Association, and was previously a member of the National Advisory Committee on Innovation which advises the Minister of Science and Technology.
Michael has more than 320 medical and scientific publications with and H-Index of 72/85 (Scopus/Google Scholar). He is a member of the Academy of Science of South Africa and has received a number of awards for his research including the South African Health Excellence Award for Scientific Excellence in 2019. Michael has been extensively involved in teaching at undergraduate and postgraduate levels, and has lectured widely on the international circuit. He is frequently solicited as a peer reviewer, and is currently on the editorial boards of Lymphatic Research and Biology and The Journal of Medical Law and Ethics. He interacts frequently with the media and writes for the lay press on scientific and medical matters.edit - Supervisoredit
BackgroundAdverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of... more
BackgroundAdverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 Test® (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population.MethodsAmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles.ResultsEven though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. T...
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The South African (SA) legislative framework follows a hierarchical structure aligned with the relevant level of government (national, provincial or local) responsible for applying and monitoring the legislation, with the overarching and... more
The South African (SA) legislative framework follows a hierarchical structure aligned with the relevant level of government (national, provincial or local) responsible for applying and monitoring the legislation, with the overarching and progressive Constitution as the supreme law. Delegated legislation (also known as secondary or subordinate legislation, e.g. regulations) ‘adds flesh’ to Acts of Parliament, or other forms of original legislation. The control and use of human tissue in South Africa is primarily governed by the National Health Act and relevant regulations, although other national acts, in differing degrees, are also relevant to this complex field. These include, among others, the Medicines and Related Substances Act, the Consumer Protection Act, the Children’s Act and the Inquest Act. Regulations generally only require ministerial and not parliamentary approval and are therefore (theoretically) easier to amend. In principle, the drafting of Acts should be preceded by...
The metastatic spread of tumor cells is responsible for the majority of cancer deaths, and with few exceptions, all cancers can metastasize. Clinical findings have long suggested that by providing a pathway for tumor cell dissemination,... more
The metastatic spread of tumor cells is responsible for the majority of cancer deaths, and with few exceptions, all cancers can metastasize. Clinical findings have long suggested that by providing a pathway for tumor cell dissemination, tumor-associated lymphatics are a key component of metastatic spread. It is not known, however, whether pre-existing vessels are sufficient to serve this function, or whether tumor cell dissemination requires de novo lymphatic formation (lymphangiogenesis) or an increase in lymphatic size. Lymphangiogenesis has traditionally been overshadowed by the greater emphasis placed on the blood vascular system (angiogenesis). This is due in part to the lack of identification of lymphangiogenic factors, as well as suitable markers that distinguish blood from lymphatic vascular endothelium. This scenario is changing rapidly after the identification of the first lymphangiogenic factor, vascular endothelial growth factor C (VEGF-C). Increased expression of VEGF-C...
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Induction of in vitro angiogenesis and upregulation of urokinase- and tissue type-plasminogen activator (uPA, tPA) expression are two hallmarks of vascular endothelial growth factor (VEGF) activity on cultured endothelial cells. We report... more
Induction of in vitro angiogenesis and upregulation of urokinase- and tissue type-plasminogen activator (uPA, tPA) expression are two hallmarks of vascular endothelial growth factor (VEGF) activity on cultured endothelial cells. We report here that neutralizing antibodies to basic fibroblast growth factor (bFGF) inhibit VEGF-induced in vitro angiogenesis in bovine microvascular endothelial (BME) cells. Analysis of VEGF receptor-2 (VEGFR-2) expression revealed no alteration in VEGFR-2 mRNA or total protein in anti-bFGF antibody-treated BME or bovine aortic endothelial (BAE) cells. Ethidium bromide/agarose gel electrophoresis on the cytosolic fraction of BME cells revealed a basal level of fragmented DNA that was increased by anti-bFGF antibodies to an extent not exceeding that observed in parallel cultures incubated with concentrations of transforming growth factor-ss1 that increase VEGF-induced in vitro angiogenesis. In both BME and BAE cells, antibodies to bFGF also decreased basal...
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Tumours are characterized by a state of chronic inflammation and are regarded as wounds that never heal. Mesenchymal stromal/stem cells (MSCs) are being considered as a possible treatment option. While MSCs can regulate the immune system,... more
Tumours are characterized by a state of chronic inflammation and are regarded as wounds that never heal. Mesenchymal stromal/stem cells (MSCs) are being considered as a possible treatment option. While MSCs can regulate the immune system, migrate to sites of inflammation, and are naturally immune-privileged, there have been contradictory reports on the role of these cells in the tumour microenvironment (TME). Some studies have suggested that MSCs promote tumourigenesis while others have suggested the contrary. To better evaluate the role of MSCs in the TME, it may be helpful to understand the role of MSCs in chronic wounds. Here, we discuss the role of MSCs in chronic wounds and extrapolate this to the TME. Chronic wounds are stuck in the inflammatory phase of wound healing, while in the case of the TME, both the inflammatory and proliferative phases are exploited. MSCs in chronic wounds promote a switch in macrophage phenotype from proinflammatory (M1) to anti-inflammatory (M2), th...
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MYO7A gene encodes unconventional myosin VIIA, which, when mutated, causes a phenotypic spectrum ranging from recessive hearing loss DFNB2 to deaf-blindness, Usher Type 1B (USH1B). MYO7A mutations are reported in nine DFNB2 families to... more
MYO7A gene encodes unconventional myosin VIIA, which, when mutated, causes a phenotypic spectrum ranging from recessive hearing loss DFNB2 to deaf-blindness, Usher Type 1B (USH1B). MYO7A mutations are reported in nine DFNB2 families to date, none from sub-Saharan Africa.In DNA, from a cohort of 94 individuals representing 92 families from the Limpopo province of South Africa, eight MYO7A variations were detected among 10 individuals. Family studies identified homozygous and compound heterozygous mutations in 17 individuals out of 32 available family members. Four mutations were novel, p.Gly329Asp, p.Arg373His, p.Tyr1780Ser, and p.Pro2126Leufs*5. Two variations, p.Ser617Pro and p.Thr381Met, previously listed as of uncertain significance (ClinVar), were confirmed to be pathogenic. The identified mutations are predicted to interfere with the conformational properties of myosin VIIA through interruption or abrogation of multiple interactions between the mutant and neighbouring residues....
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Clinical research in high-income countries is increasingly demonstrating the cost- effectiveness of clinical pharmacogenetic (PGx) testing in reducing the incidence of adverse drug reactions and improving overall patient care. Medications... more
Clinical research in high-income countries is increasingly demonstrating the cost- effectiveness of clinical pharmacogenetic (PGx) testing in reducing the incidence of adverse drug reactions and improving overall patient care. Medications are prescribed based on an individual’s genotype (pharmacogenes), which underlies a specific phenotypic drug response. The advent of cost-effective high-throughput genotyping techniques coupled with the existence of Clinical Pharmacogenetics Implementation Consortium (CPIC) dosing guidelines for pharmacogenetic “actionable variants” have increased the clinical applicability of PGx testing. The implementation of clinical PGx testing in sub-Saharan African (SSA) countries can significantly improve health care delivery, considering the high incidence of communicable diseases, the increasing incidence of non-communicable diseases, and the high degree of genetic diversity in these populations. However, the implementation of PGx testing has been sluggish...
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The potential for human adipose-derived stromal cells (hASCs) to be used as a therapeutic product is being assessed in multiple clinical trials. However, much is still to be learned about these cells before they can be used with... more
The potential for human adipose-derived stromal cells (hASCs) to be used as a therapeutic product is being assessed in multiple clinical trials. However, much is still to be learned about these cells before they can be used with confidence in the clinical setting. An inherent characteristic of hASCs that is not well understood is their heterogeneity. The aim of this exploratory study was to characterize the heterogeneity of freshly isolated hASCs after two population doublings (P2) using single-cell transcriptome analysis. A minimum of two subpopulations were identified at P2. A major subpopulation was identified as contractile cells which, based on gene expression patterns, are likely to be pericytes and/or vascular smooth muscle cells (vSMCs).
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As of 8 January 2021, there were 86,749,940 confirmed coronavirus disease 2019 (COVID-19) cases and 1,890,342 COVID-19-related deaths worldwide, as reported by the World Health Organization (WHO). In order to address the COVID-19 pandemic... more
As of 8 January 2021, there were 86,749,940 confirmed coronavirus disease 2019 (COVID-19) cases and 1,890,342 COVID-19-related deaths worldwide, as reported by the World Health Organization (WHO). In order to address the COVID-19 pandemic by limiting transmission, an intense global effort is underway to develop a vaccine against SARS-CoV-2. The development of a safe and effective vaccine usually requires several years of pre-clinical and clinical stages of evaluation and requires strict regulatory approvals before it can be manufactured in bulk and distributed. Since the global impact of COVID-19 is unprecedented in the modern era, the development and testing of a new vaccine are being expedited. Given the high-level of attrition during vaccine development, simultaneous testing of multiple candidates increases the probability of finding one that is effective. Over 200 vaccines are currently in development, with over 60 candidate vaccines being tested in clinical trials. These make u...
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The recurrence and/or lack of response of certain tumors to radio-and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and... more
The recurrence and/or lack of response of certain tumors to radio-and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse. Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignancy worldwide with the highest incidence occurring in East Asia and eastern and southern Africa. Several cellular subpopulations believed to have CSC properties have been isolated from HNSCCs, but at present, identification and characterization of CSCs remains an experimental challenge with no established or standardized protocols in place to confirm their identity. In this review we discuss current approaches to the study of CSCs with a focus on HNSCCs, particularly in the context of what this might mean from a therapeutic perspective.
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The use of stem cells in regenerative medicine, including tissue engineering and transplantation, has generated a great deal of enthusiasm. Mesenchymal stromal/stem cells (MSCs) can be isolated from various tissues, most commonly, bone... more
The use of stem cells in regenerative medicine, including tissue engineering and transplantation, has generated a great deal of enthusiasm. Mesenchymal stromal/stem cells (MSCs) can be isolated from various tissues, most commonly, bone marrow but more recently adipose tissue, dental pulp, and Wharton’s jelly, to name a few. MSCs display varying phenotypic profiles and osteogenic differentiating capacity depending and their site of origin. MSCs have been successfully differentiated into osteoblasts both in vitro an in vivo but discrepancies exist when the two are compared: what happens in vitro does not necessarily happen in vivo, and it is therefore important to understand why these differences occur. The osteogenic process is a complex network of transcription factors, stimulators, inhibitors, proteins, etc., and in vivo experiments are helpful in evaluating the various aspects of this osteogenic process without distractions and confounding variables. With that in mind, the results...
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Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of... more
Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using the murine 3T3-L1 preadipocyte cell line and murine experimental animal models. Translation of these findings to the human setting requires confirmation using experimental models of human origin. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is an attractive model to study adipogenesis in vitro. Differences in the ability of MSCs isolated from different sources to undergo adipogenic differentiation, may be useful in investigating elements responsible for regulating adipogenic differentiation potential. Genes involved may be divided into three broad categories: early, intermediate and late-stage regulators. Preadipocyte factor-1 (Pref-1) is an earl...
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The search for novel anti-cancer compounds which can circumvent chemotherapeutic drug resistance and limit systemic toxicity remains a priority. 2-Ethyl-3-O-sulphamoyl-estra-1,3,5(10)15-tetraene-3-ol-17one (ESE-15-one) and... more
The search for novel anti-cancer compounds which can circumvent chemotherapeutic drug resistance and limit systemic toxicity remains a priority. 2-Ethyl-3-O-sulphamoyl-estra-1,3,5(10)15-tetraene-3-ol-17one (ESE-15-one) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) are sulphamoylated 2-methoxyestradiol (2-ME) analogues designed by our research team. Although their cytotoxicity has been demonstrated in vitro, the temporal and mechanistic responses of the initiated intracellular events are yet to be determined. In order to do so, assays investigating the compounds’ effects on microtubules, cell cycle progression, signalling cascades, autophagy and apoptosis were conducted using HeLa cervical- and MDA-MB-231 metastatic breast cancer cells. Both compounds reversibly disrupted microtubule dynamics as an early event by binding to the microtubule colchicine site, which blocked progression through the cell cycle at the G1/S- and G2/M transitions. This was supported by increa...
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The pandemic caused by SARS-CoV-2 has infected more than 94 million people worldwide (as of 17 January 2020). Severe disease is believed to be secondary to the cytokine release syndrome (CRS or “cytokine storm”) which causes local tissue... more
The pandemic caused by SARS-CoV-2 has infected more than 94 million people worldwide (as of 17 January 2020). Severe disease is believed to be secondary to the cytokine release syndrome (CRS or “cytokine storm”) which causes local tissue damage as well as multi-organ dysfunction and thrombotic complications. Due to the high mortality rates in patients receiving invasive ventilation, practice has changed from “early-intubation” for acute respiratory distress syndrome (ARDS) to a trial of non-invasive ventilation (NIV) or high flow nasal cannula (HFNC) oxygen. Reports indicating the benefit of NIV and HFNC have been encouraging and have led to more than 20,000 such devices being manufactured and ready for roll-out in South Africa (SA) as of July 2020. The need to identify drugs with clear clinical benefits has led to an array of clinical trials, most of which are repurposing drugs for COVID-19. The treatment landscape reflects the need to target both the virus and its effects such as ...
The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization.... more
The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte co...
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Somatic cell nuclear transfer (SCNT) has been an area of interest in the field of stem cell research and regenerative medicine for the past 20 years. The main biological goal of SCNT is to reverse the differentiated state of a somatic... more
Somatic cell nuclear transfer (SCNT) has been an area of interest in the field of stem cell research and regenerative medicine for the past 20 years. The main biological goal of SCNT is to reverse the differentiated state of a somatic cell, for the purpose of creating blastocysts from which embryonic stem cells (ESCs) can be derived for therapeutic cloning, or for the purpose of reproductive cloning. However, the consensus is that the low efficiency in creating normal viable offspring in animals by SCNT (1–5%) and the high number of abnormalities seen in these cloned animals is due to epigenetic reprogramming failure. In this review we provide an overview of the current literature on SCNT, focusing on protocol development, which includes early SCNT protocol deficiencies and optimizations along with donor cell type and cell cycle synchrony; epigenetic reprogramming in SCNT; current protocol optimizations such as nuclear reprogramming strategies that can be applied to improve epigenet...
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Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat... more
Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset o...
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The probability of a Black African finding a matched unrelated donor for a hematopoietic stem cell transplant is minimal due to the high degree of genetic diversity amongst individuals of African origin. This problem could be resolved in... more
The probability of a Black African finding a matched unrelated donor for a hematopoietic stem cell transplant is minimal due to the high degree of genetic diversity amongst individuals of African origin. This problem could be resolved in part by the establishment of a public cord blood (CB) stem cell bank. The high prevalence of human immunodeficiency virus (HIV) amongst women attending antenatal clinics in sub-Saharan Africa together with the risk of mother-to-child transmission increases the risk of transplant transmissible infection. In addition to screening the mother in a period inclusive of 7 days prior to the following delivery, we propose that all CB units considered for storage undergo rigorous and reliable screening for HIV. The Ultrio-plus® assay is a highly specific and sensitive test for detecting HIV, hepatitis-B and hepatitis-C viruses in peripheral blood. We validated the Ultrio-plus® assay for analytical sensitivity in detecting HIV in CB at the level of detection o...
There is still much to learn about the cells used for cell- and gene-based therapies in the clinical setting. Stem cells are found in virtually all tissues in the human body. As a result, cells isolated from these tissues are a... more
There is still much to learn about the cells used for cell- and gene-based therapies in the clinical setting. Stem cells are found in virtually all tissues in the human body. As a result, cells isolated from these tissues are a heterogeneous population consisting of various subpopulations including stem cells. Several strategies have been used to isolate and define the subpopulations that constitute these heterogeneous populations, one of which is the side population (SP) assay. SP cells are identified by their ability to efflux a fluorescent dye at a rate that is greater than the main cell population. This elevated rate of dye efflux has been attributed to the expression of members of the ATP-binding cassette (ABC) transporter protein family. SP cells have been identified in various tissues. In this review, we discuss the research to date on SP cells, focussing on SP cells identified in haematopoietic stem cells, adipose-derived stromal cells, and dental pulp.
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The field of dermal fillers is evolving rapidly and numerous products are currently on the market. Biodegradable polymers such as polycaprolactone (PCL) have been found to be compatible with several body tissues, and this makes them an... more
The field of dermal fillers is evolving rapidly and numerous products are currently on the market. Biodegradable polymers such as polycaprolactone (PCL) have been found to be compatible with several body tissues, and this makes them an ideal material for dermal filling purposes. Hollow PCL spheres were developed by the Council for Scientific and Industrial Research (CSIR) to serve both as an anchor point and a "tissue harbour" for cells. Particles were tested for cytotoxicity and cell adherence using mouse embryo fibroblasts (MEF). MEFs adhered to the particles and no significant toxic effects were observed based on morphology, cell growth, cell viability and cell cycle analysis, suggesting that the particles are suitable candidates for cell delivery systems in an in vivo setting. The objective of providing a "tissue harbour" was however not realized, as cells did not preferentially migrate into the ported particles. In vivo studies were conducted in BALB/c mice ...
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Pooled human platelet lysate (pHPL) has been used to expand adipose-derived stromal cells (ASCs) and can be formulated using fresh or expired buffy coats (BCs) which are then resuspended in either plasma or an additive solution. Not much... more
Pooled human platelet lysate (pHPL) has been used to expand adipose-derived stromal cells (ASCs) and can be formulated using fresh or expired buffy coats (BCs) which are then resuspended in either plasma or an additive solution. Not much is known about the effects that expired products and additive solutions have on ASC expansion, and the need for quality control and release criteria has been expressed. This pilot study compared proliferation, cell size, morphology and immunophenotype of ASCs expanded in the different pHPL alternatives versus foetal bovine serum (FBS). Quality control criteria were assessed prior to and during the manufacture of the pHPL alternatives. ASCs were then expanded in 1%, 2.5%, 5% or 10% of the different pHPL alternatives or in 10% FBS. Cell size, morphology, cell number and immunophenotype were measured using microscopy and flow cytometry. The majority of the pHPL alternatives were within the recommended ranges for the quality control criteria. ASCs expan...
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Interest in reactive oxygen species and adipocyte differentiation/adipose tissue function is steadily increasing. This is due in part to a search for alternative avenues for combating obesity, which results from the excess accumulation of... more
Interest in reactive oxygen species and adipocyte differentiation/adipose tissue function is steadily increasing. This is due in part to a search for alternative avenues for combating obesity, which results from the excess accumulation of adipose tissue. Obesity is a major risk factor for complex disorders such as cancer, type 2 diabetes, and cardiovascular diseases. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is often used as a model for studying adipogenesis in vitro. A key focus is the effect of both intra- and extracellular reactive oxygen species (ROS) on adipogenesis. The consensus from the majority of studies is that ROS, irrespective of the source, promote adipogenesis.The effect of ROS on adipogenesis is suppressed by antioxidants or ROS scavengers. Reactive oxygen species are generated during the process of adipocyte differentiation as well as by other cell metabolic processes. Despite many studies in this field, it is still not po...
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Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to... more
Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles. To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced. Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity. Hence, CYP2D6 genotype contributes to treatment outcome and may be useful for guiding drug therapy. Future investigations in a larger patient population are planned to support these preliminary findings.
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When HIV was initially discovered as the causative agent of AIDS, many expected to find a vaccine within a few years. This has however proven to be elusive; it has been approximately 30 years since HIV was first discovered, and a suitable... more
When HIV was initially discovered as the causative agent of AIDS, many expected to find a vaccine within a few years. This has however proven to be elusive; it has been approximately 30 years since HIV was first discovered, and a suitable vaccine is still not in effect. In 2009, a paper published by Hutter et al. reported on a bone marrow transplant performed on an HIV positive individual using stem cells that were derived from a donor who was homozygous for a mutation in the CCR5 gene known as CCR5 delta-32 (Δ32) (Hütter et al., 2009). The HIV positive individual became HIV negative and remained free of viral detection after transplantation despite having halted anti-retroviral (ARV) treatment. This review will focus on CCR5 as a key component in HIV immunity and will discuss the role of CCR5 in the control of HIV infection.
In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous... more
In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) plays an important role in this context, and it aims at specifically guiding the translation of clinically relevant and evidence-based pharmacogenomics research. In this forward-looking analysis, we make particular reference to several of the CPIC guidelines and their role in guiding the treatment of highly relevant diseases, ...
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Adipose-derived stromal cells (ASCs) are being used extensively in clinical trials. These trials require that ASCs are prepared using good manufacturing practices (GMPs) and are safe for use in humans. The majority of clinical trials in... more
Adipose-derived stromal cells (ASCs) are being used extensively in clinical trials. These trials require that ASCs are prepared using good manufacturing practices (GMPs) and are safe for use in humans. The majority of clinical trials in which ASCs are expanded make use of fetal bovine serum (FBS). While FBS is used traditionally in the research setting for in vitro expansion, it does carry the risk of xenoimmunization and zoonotic transmission when used for expanding cells destined for therapeutic purposes. In order to ensure a GMP quality product for cellular therapy, in vitro expansion of ASCs has been undertaken using xeno-free (XF), chemically-defined, and human blood-derived alternatives. These investigations usually include the criteria proposed by the International Society of Cellular Therapy (ISCT) and International Fat Applied Technology Society (IFATS). The majority of studies use these criteria to compare plastic-adherence, morphology, the immunophenotype and the trilinea...
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Research Interests: Lactation, Gene expression, Cell line, Pregnancy, Humans, and 15 moreMice, Female, Animals, Polymerase Chain Reaction, Clinical Sciences, Epithelium, Epithelial cells, Mammary gland, Amino Acid Sequence, Base Sequence, Milk Protein, Biochemistry and cell biology, Milk proteins, Hepatocyte Growth Factor, and Molecular Sequence Data
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There can be no doubt that the finest creator of beauty is Mother Nature. And in many ways, science is the exploration of this beauty and of the mechanisms that have created it. Microscopy, as a technique in scientific investigation, has... more
There can be no doubt that the finest creator of beauty is Mother Nature. And in many ways, science is the exploration of this beauty and of the mechanisms that have created it. Microscopy, as a technique in scientific investigation, has had a key role in uncovering nature's beauty, which has led some to propose that microscopy could be described as an art or even an art form. But is this claim justified?