The self-renewing population (SRP) plays a pivotal role as the primary cell bank of hematopoietic stem cells (HSCs) in the bone marrow. This population replenishes precursor cells and significantly contributes to the restoration of hematopoietic hierarchical progenitors such as myeloid, lymphoid, and erythroid intermediates, which subsequently form short-lived terminal lineages. These cells generated by SRPs actively engage in immune functions, particularly countering infection, cancer, and radiation-attenuated immunity post-exposure. At the forefront, SRPs that regenerate exhausted precursor cells and progenitors are particularly Long-Term Culture-Initiating Cells (LTC-IC). These cells, particularly play a crucial role in the rescue of people who have received critical doses of radiation. The direct delivery of SRPs from donor to recipient is an effective strategy, but it faces severe challenges due to the inability to harvest them after mobilization into circulation in sufficient numbers.
A traditional method, which consists of direct aspiration from the iliac bone marrow or in vitro expansion, is invasive. Alternative cytokine treatment is exorbitantly expensive as it requires them in very high concentrations. Consequently, finding alternative approaches to obtain the self-renewing SRPs or progenitor stem cell population is imperative. This may include exploring gene therapy or combination therapy involving cytokines and chemical molecules to enhance their number.
This Research Topic aims to focus on currently established methods and detailed protocols used in the field. The collection will rigorously study and analyze their potential role in possibly formulating procedures that can enable them to sustain their self-renewal by conserving stemness. By gathering insights into advancements in HSC proliferation and self-renewal maintenance, efforts to collect them should seek ongoing dialogues on the progress in the field.
Areas to be covered in this Research topic may include but are not limited to:
• Role of Self-Renewing Population (SRP): research investigating computational models and methodologies that analyze the role of SRPs as the primary cell bank of hematopoietic stem cells in the bone marrow. This could involve bioinformatics approaches to understand the genetic and epigenetic regulation governing SRP function.
• Advanced Techniques in HSC Proliferation: cutting-edge technologies, including Next-Generation Sequencing (NGS), genome-wide association studies (GWAS), and flow cytometry, to dissect the molecular mechanisms underlying HSC proliferation. This may involve examining how these techniques contribute to our understanding of the regulatory networks governing hematopoiesis.
• Innovative Approaches to Stem Cell Delivery: novel methods for transplanting SRPs from donor to recipient, considering advancements in human leukocyte antigens (HLA) barcoding technologies and CRISPR-based gene therapies. Assess the potential of these techniques to overcome challenges associated with mobilization and transplantation, offering more efficient and less invasive alternatives.
• Combination Therapies for HSC Maintenance: studies exploring the use of combination therapies, involving cytokines and chemical molecules, to enhance the self-renewal of progenitor stem cells. This could include the application of cell culture, molecular biology, cell biology, and computational models to predict the synergistic effects of different therapeutic agents and optimize their use in maintaining HSC self-renewal.
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