Cellular reprogramming of human acute myeloid leukemia patient somatic cells
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Abstract Hematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. Embryonic stem cell-based directed differentiation and direct reprogramming of somatic cells provide excellent tools for the potential generation of hematopoietic stem cells usable in the clinic for cellular therapies. In addition to blood stem cell transplantation, mature blood cells such as red blood cells, platelets, and engineered T cells have also been increasingly used to treat several diseases. Besides cellular therapies, induced blood progenitor cells generated from autologous sources (either induced pluripotent stem cells or somatic cells) can be useful for disease modeling of bone marrow failures and acquired blood disorders. However, although great progress has been made toward these goals, we are still far from the use of in vitro-derived blood products in the clinic. We review the current state of knowledge on the directed differentiation of embryonic stem cells and the reprogramming of somatic cells toward the generation of blood stem cells and derivatives. Significance Hematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. The current state of knowledge on the directed differentiation of embryonic stem cells and the reprogramming of somatic cells toward the generation of blood stem cells and derivatives is reviewed.
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Autologous hematopoietic stem cells are excellent targets for stem cell gene therapy for HIV. Previous and also upcoming clinical trials utilize these types of stem cells. They can be obtained either from the bone marrow or by mobilization and subsequent apheresis from the peripheral blood. After transplantation, there is no rejection issue; however, a high-enough transduction efficiency to elicit a clinical benefit is difficult to obtain. Selection of transduced cells could be a solution to this problem. Anti-HIV gene-modified hematopoietic stem cells could also be generated from pluripotent stem cells that were gene modified with anti-HIV genes. A pluripotent, anti-HIV gene-modified cell clone could be used to generate enough hematopoietic stem cells to engraft the recipient. The generation of a patient's own gene-modified stem cells is possible by the use of autologous, induced pluripotent stem cells.
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Over the past 25years, stem cell therapies have become an attractive field to treat and investigate neurodegenerative diseases.Stem cells are undifferentiated cells with the ability of proliferation, regeneration, differentiation in other cells.Stem cells are divided into two categories of embryonic and adult.In some other classification stem cells are divided into Totipotent, Multipotent and Unipotent cells.Stem cell therapy used in different diseases like neurodegenerative disease, inflammatory bowel disease, liver disease, diabetes, heart disease, bone disease, renal disease, chronic wounds, graft-versus-host disease, sepsis, lymphoblastic leukemia, myeloid leukemia, thalassemia, multiple myeloma, cycle cell anemia and respiratory diseases.In the current review, we detail the current state of stem cell research in neurodegenerative diseases, with a brief introduction about stem cell therapy.We also discuss the hurdles associated with stem cell therapies from bench to bedside.In this review, the final goal is the evaluation of cell therapy in the treatment of different neurodegenerative diseases like Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Alzheimer, Spinal muscular atrophy, Stroke and the burden of these diseases on the society underline the need for the practice of stem cell therapies.
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Human induced pluripotent stem (iPS) cells have been generated from various cell types including blood cells, and offer certain advantages as a starting population for reprogramming postnatal somatic cells. Unlike adult stem cells, iPS cells can proliferate limitlessly in culture while retaining their potential to differentiate into any cell type, including hematopoietic lineages. Derivation of patient-specific iPS cells, in combination with improved hematopoietic differentiation protocols, provides an alternative to generate histocompatible stem cells for bone marrow transplantation. In addition, the ability to reprogram blood cells and redifferentiate iPS cells back to hematopoietic lineages provides opportunities to establish novel models for acquired and inherited blood diseases. This article will summarize recent progress in human iPS cells derived from blood cells and hematopoietic differentiation from iPS cells. Advantages of blood as a source for reprogramming and applications in regenerative medicine will be discussed.
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Purpose of reviewHematopoietic cell transplantation (HCT) is a successful treatment modality for patients with malignant and nonmalignant disorders, usually when no other treatment option is available. The cells supporting long-term reconstitution after HCT are the hematopoietic stem cells (HSCs), w
Ectopic expression
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The functions of retinoic acid (RA), a potent morphogen with crucial roles in embryogenesis including developmental hematopoiesis, have not been thoroughly investigated in the human setting. Using an in vitro model of human hematopoietic development, we evaluated the effects of RA signaling on the development of blood and on generated hematopoietic progenitors. Decreased RA signaling increases the generation of cells with a hematopoietic stem cell (HSC)-like phenotype, capable of differentiation into myeloid and lymphoid lineages, through two separate mechanisms: by increasing the commitment of pluripotent stem cells toward the hematopoietic lineage during the developmental process and by decreasing the differentiation of generated blood progenitors. Our results demonstrate that controlled low-level RA signaling is a requirement in human blood development, and we propose a new interpretation of RA as a regulatory factor, where appropriate control of RA signaling enables increased generation of hematopoietic progenitor cells from pluripotent stem cells in vitro.
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This chapter summarizes some basic features of stem cells, including their defining properties, the range of different stem cell types, and the ways in which they can be identified and characterized. It considers the therapeutic application of stem cells. Stem cells with only a limited period of activity underlie the formation of the embryo from a single fertilized cell through to the fully formed fetus. The precise way in which a transplantation assay of stem cells is performed depends on the type of cell being characterized and whether it is a same species assay or a xenograft. The assay of hematopoietic stem cells (HSCs) involves irradiation of the host mouse to completely ablate its resident bone marrow stem cells and hematopoietic system. Cellular therapy that can be performed in the fetus is also a special case because of the status of the immune system.
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