Fatima S.F. Aerts Kaya

Hacettepe University Graduate School of Health Sciences, Ankara, Turkey · Department of Stem Cell Sciences

RAG2 deficiency is characterized by a lack of B and T lymphocytes, causing severe lethal infections. Currently, RAG2 deficiency is treated with a Hematopoietic Stem Cell transplantation (HSCT). Most conditioning regimens used before HSCT consist of alkylating myelotoxic agents with or without irradiation and affect growth and development of pediatr...

Background/aim Griscelli Syndrome Type 2 (GS-2) is a rare, inherited immune deficiency caused by a mutation in the RAB27A gene. The current treatment consists of hematopoietic stem cell transplantation, but a lack of suitable donors warrants the development of alternative treatment strategies, including gene therapy. The development of mutation-spe...

Inflammatory bowel disease (IBD) is characterized by a chronically dysregulated immune response in the gastrointestinal tract. Bone marrow multipotent mesenchymal stromal cells have an important immunomodulatory function and support regeneration of inflamed tissue by secretion of soluble factors as well as through direct local differentiation. CXCR...

Leukodystrophies are a heterogenous group of inherited, degenerative encephalopathies, that if left untreated, are often lethal at an early age. Although some of the leukodystrophies can be treated with allogeneic hematopoietic stem cell transplantation, not all patients have suitable donors, and new treatment strategies, such as gene therapy, are...

Comparison of different methods for genetic correction of Griscelli Syndrome type II-derived stem cells This work was supported by grants from the Scientific and Technological Research Council of Turkey (TÜBİTAK) project nr. 219S675 and the Hacettepe University Scientific Project Coordination Unit (BAP) project nr. TUK-2019-17760. Background: G...

Background: Primary immunodeficiencies (PID) are characterized by the absence or dysfunction of lymphocytes and affect both cellular and humoral adaptive immunity. RAG2 (Recombination activating gene 2) deficiency is characterized by a lack of both mature B and T lymphocytes, causing severe viral and bacterial infections that are usually lethal bef...

RAG2 deficiency is characterized by a lack of B and T lymphocytes, causing severe lethal infections. Currently, RAG2 deficiency is treated with a Hematopoietic Stem Cell transplantation (HSCT). Most conditioning regimens used before HSCT consist of alkylating myelotoxic agents with or without irradiation and affect growth and development of pediatr...

Small GTPases have been shown to play an important role in several cellular functions, including cytoskeletal remodeling, cell polarity, intracellular trafficking, cell-cycle, progression and lipid transformation. The Ras-associated binding (Rab) family of GTPases constitutes the largest family of GTPases and consists of almost 70 known members of...

Here, we describe a protocol for reprogramming of bone marrow–derived multipotent mesenchymal stromal/stem cells to obtain induced pluripotent stem cells from patients with primary immune deficiencies using lentiviral vectors, followed by hematopoietic differentiation of the MSC-derived iPSCs. This protocol is particularly helpful in cases where it...

Fanconi anemia (FA) is a rare genetic disorder characterized by genomic instability, developmental defects, and bone marrow (BM) failure. Hematopoietic stem cells (HSCs) in BM interact with the mesenchymal stem/stromal cells (MSCs); and this partly sustains the tissue homeostasis. MicroRNAs (miRNAs) can play a critical role during these interaction...

Despite a vast amount of different methods, protocols and cryoprotective agents (CPA), stem cells are often frozen using standard protocols that have been optimized for use with cell lines, rather than with stem cells. Relatively few comparative studies have been performed to assess the effects of cryopreservation methods on these stem cells. Dimet...

Despite a vast amount of different methods, protocols and cryoprotective agents (CPA), stem cells are often frozen using standard protocols that have been optimized for use with cell lines, rather than with stem cells. Relatively few comparative studies have been performed to assess the effects of cryopreservation methods on these stem cells. Dimet...

Lysosomal storage disorders (LSDs) are rare inborn errors of metabolism caused by defects in lysosomal function. These diseases are characterized by accumulation of completely or partially degraded substrates in the lysosomes leading to cellular dysfunction of the affected cells. Currently, enzyme replacement therapies (ERTs), treatments directed a...

Background Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a protein involved in vesicle trafficking and consequent loss of function of in particular cytotoxic T and NK cells. Induced pluripotent stem cells (iPSC) express genes associ...

Multipotent mesenchymal stromal cells (MSC) can be isolated from many tissues, including bone marrow (BM) and placenta (PL). Human placenta can be obtained readily without invasive procedures. There may be differences, however, in differentiation capacity and immunomodulation by MSC isolated from BM or PL. The early pregnancy factor (heat shock pro...

In recent years, multipotent mesenchymal stromal cells (MSCs) have demonstrated tremendous potential for use in regenera-tive medicine. CXCR4, the receptor for CXCL12, is highly expressed by bone marrow (BM) MSCs and the CXCR4/CXCL12 axis has been shown to be important for migration and homing of BM-MSCs. Typically, MSCs used for clinical applicati...

Although G-CSF mobilized peripheral blood stem cell (PBSC) transplantation is commonly used in adults, bone marrow (BM) is still the preferred stem cell source in pediatric stem cell transplantation. Despite the fact that G-CSF is increasingly being used to enhance the hematopoietic stem/progenitor cell (HSPC) yield in BM trans-plantation (G-BM), t...

Since the start of the coronavirus SARS-CoV2 (COVID-19) outbreak in China, in the end of 2019, the virus has rapidly spread throughout the World, causing a path of destruction behind it, with mortality figures exceeding 7.000.000 globally, and a death toll reaching numbers of over 400.000. Economically, the pandemic has been estimated to cause a Wo...

In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of hematopoietic stem cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs...

Differentiation, self-renewal and quiescence of Hematopoietic stem cells (HSCs) is tightly regulated in order to protect the HSCs from the strain of constant cell division and depletion of the stem cell pool. The neurotransmitter Neuropeptide Y (NPY) is released from sympathetic nerves in the bone marrow and has been shown to indirectly affect HSC...

The newly developed 6-hydroxychromanol SUL-109 was shown to provide protection during hypothermic storage of several cell lines, but has not been evaluated in hematopoietic stem cells (HSCs). Hypothermic preservation of HSCs would be preferred over short-term cryopreservation to prevent cell loss during freezing/thawing and be particularly useful f...

The bone marrow (BM) hematopoietic niche is the microenvironment where in the adult hematopoietic stem and progenitor cells (HSPCs) are maintained and regulated. This regulation is tightly controlled through direct cell-cell interactions with mesenchymal stromal stem (MSCs) and reticular cells, adipocytes, osteoblasts and endothelial cells, through...

Mucolipidosis type II (ML-II, I-cell disease) is a fatal inherited lysosomal storage disease caused by a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase. A characteristic skeletal phenotype is one of the many clinical manifestations of ML-II. Since the mechanisms underlying these skeletal defects in ML-II are not completely unders...

Griscelli Syndrome Type 2 (GS-2) is a rare inherited immune deficiency caused by mutations in the RAB27A gene and is characterized by silver grey hair, hypopigmentation, fever and infections. Currently, the only available treatment is hematopoietic stem cell transplantation (HSCTx). Here we cultured bone marrow Mesenchymal Stem Cells (MSCs) from GS...

Stem cell therapy offers a great advantage for the development of new treatments in the field of regenerative and restorative medicine. However, the use of stem cell therapies and their clinical indications can even be further improved using genetic modification of the cells. Due to the high level of consanguineous marriages in Turkey, the country...

Purpose Transient hypogammaglobulinemia of infancy (THI) is a common immunodeficiency, but definitive diagnosis can only be made retrospectively. While the pathogenesis is still unknown, abnormalities have been reported in the B cell compartment. In this study, we analysed the B cell subsets of patients with an initial THI diagnosis (n = 20) and co...

Transforming growth factor beta (TGF-β) secretion from cells in the bone marrow (BM) niche affects hematopoietic stem cell (HSC) fate and has a cardinal role in HSC quiescence. BM mesenchymal stem cells (BM-MSCs), a component of the BM niche, may produce abnormal levels of TGF-β in Fanconi anemia (FA) and may play a role in bone marrow failure. Her...

Peripheral blood stem cell (PBSC) transplantation has become an established treatment option for a range of malignant and inherited diseases. PBSCs are usually cryopreserved in the presence of dimethyl sulfoxide (DMSO) and stored in liquid nitrogen. However, cryopreservation and thawing of PBSCs may affect cell viability, resulting in delayed engra...

Granulocyte Colony-Stimulating Factor (G-CSF) is a well-known hematopoietic stem cell (HSC) mobilizing agent used in both allogeneic and autologous transplantation. However, a proportion of patients or healthy donors fail to mobilize sufficient number of cells. New mobilization agents are therefore needed. Endocannabinoids (eCBs) are endogenous lip...

Bone marrow mesenchymal stem cells (BM‐MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM‐MSCs is currently unknown. Here, we assessed how obesity affects the function of BM‐MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM‐MSCs were...

Human mesenchymal stromal cells (MSCs) from different parts of the body (i.e. bone marrow -BM-) have distinct cellular and molecular features including global gene expression profile. Quantitive PCR (qPCR) is a reliable method used in quantification of gene expression. Correct assessment of target gene expression mostly depends on the reference gen...

Polyhydroxybutyrate (PHB) is a polymer used to restore tissues or regenerate bones. However, its compatibility with human bone marrow-derived mesenchymal stem cells (MSCs) has not been examined. PHB membranes of random (r-PHB) or aligned (a-PHB) electrospun nanofibers that generate bone and spinal axon scaffolds were combined with human MSCs. The a...

Hematopoetik Kök ve Projenitör Hücreler (HKPH) kendilerini yenileyebilmekte ve ihtiyaca göre devamlı olarak, periferik kan için tüm olgunlaşmış kan hücrelerini yapmaktadır. Bu makalenin ilk bölümünde HKPH’lerin in vivo ve in vitro kendini yenilemesi için önemli olan hematopoetik büyüme faktörleri ve onların reseptörleri tartışılmaktadır. HKPH’lerin...

Introduction Imatinib Mesylate (IM) is a tyrosine kinase inhibitor (TKI), which targets Platelet Derived Growth Factor Receptor (PDGF-R), c-kit and BCR-ABL and is used in the treatment of Gastrointestinal Stromal Tumors (GIST) and Chronic Myeloid Leukemia (CML). Patients using Imatinib for a long time display abnormalities in bone metabolism (Vandy...

Stem cell studies hold enormous potential for development of new therapies for tissue regeneration and repair. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into a variety of non-hematopoietic tissues and contribute maintenance of healthy hematopoiesis by providing supportive cellular microenvironment into BM. Here, we investigated...

Introduction: Lactic acid bacteria (LAB) have been studied for their health-promoting and immunomodulatory effects. The main field of research has been in gastrointestinal tract. In the past few years LAB have also been investigated in the oral health perspective. We studied competitive adhesion of Lactobacillus strains with Porpyhromonas gingivali...

5-Androstene-3β,17β-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation...

Deficient thymopoiesis and retarded recovery of naive CD4(+) T cells are important determinants of insufficient immune-competence following hematopoietic stem cell transplantation (HSCT). Although keratinocyte growth factor (KGF) may protect the thymic epithelium, stem cell factor (SCF) is involved in early thymopoiesis. We evaluated whether KGF al...

Extensive studies have demonstrated the potential applications of bone marrow-derived mesenchymal stem cells (BM-MSCs) as regenerative or immunosuppressive treatments in the setting of organ transplantation. The aims of the present study were to explore the presence and mobilization of mesenchymal stem cells (MSCs) in adult human liver grafts and t...

Pompe disease (acid alpha-glucosidase deficiency) is a lysosomal glycogen storage disorder characterized in its most severe early-onset form by rapidly progressive muscle weakness and mortality within the first year of life due to cardiac and respiratory failure. Enzyme replacement therapy prolongs the life of affected infants and supports the cond...

Host immune responses play a major role in clearance of viral infections from the body, and may limit long-term expression and clinical efficacy of viral vectors. Methods to prevent these immune responses may also increase the risk for infections, recombination with wild type virus and affect biodistribution, persistence, shedding and transmission....

Malignant infantile osteopetrosis (MIOP) is a disorder of osteoclasts characterized by defective bone resorption and death in infancy. The multipotent mesenchymal stromal cells (MSC) and their progeny (osteoblasts) are major components of the bone marrow (BM) microenvironment and are found in close contact with cells of hematopoietic origin, includ...

Flt3/flk2 belongs to the class III hematopoietic growth factor receptors with intrinsic kinase activity, ligand-activated tyrosine phosphorylation and a central role in early stages of hematopoiesis. Flt3-ligand (FL) has been shown to enhance the effects of several growth factors, including Granulocyte-colony stimulating factor (G-CSF). In this stu...

5-AED (5-androstene-3β,17β-diol) is a naturally occurring adrenal cortical steroid, which displays radioprotective effects in both rodents and non-human primates, resulting in accelerated multilineage hematopoiesis and enhanced survival after total body irradiation (TBI), including a 1-log accelerated CD34+ cell reconstitution in bone marrow of non...

Bone marrow(BM) is considered to be one of the large and complex organs of the human body and is the most important site of hematopoiesis after birth [1]. It is composed of stroma, hematopoietic cords and sinusoidal capillaries. Under normal conditions, the production of blood is exactly adjusted to the organism's needs (homeostasis) and is both re...

5-androstene-3β,17β-diol, a naturally occurring adrenal steroid, has been shown to protect mice exposed to γ ray total body irradiation (TBI), as apparent by enhanced survival, stimulated myelopoiesis and elevated nadirs of neutrophils and platelets. In the present study, rhesus monkeys (Macaca mulatta; n=8) were subjected to the midlethal dose of...