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Related Concept Videos

Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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pH Regulation in Cells01:28

pH Regulation in Cells

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pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
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Multipotency of Hematopoietic Stem Cells01:19

Multipotency of Hematopoietic Stem Cells

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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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Role of Hematopoietic Growth Factors01:28

Role of Hematopoietic Growth Factors

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Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Hematopoiesis01:21

Hematopoiesis

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The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
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Retroviral Infection of Murine Embryonic Stem Cell Derived Embryoid Body Cells for Analysis of Hematopoietic Differentiation
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pH regulates hematopoietic stem cell potential via polyamines.

Sachin Kumar1,2, Jeffrey D Vassallo1, Kalpana J Nattamai1

  • 1Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati, OH, USA.

EMBO Reports
|March 21, 2023
PubMed
Summary
This summary is machine-generated.

Maintaining hematopoietic stem cell (HSC) potential ex vivo is crucial. Cultivating HSCs at pH 6.9 for two days preserves their function and enhances transplantation ability by reducing polyamines.

Keywords:
DFMOHSCsex vivopHpolyamine

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Phenotypic Analysis and Isolation of Murine Hematopoietic Stem Cells and Lineage-committed Progenitors
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Phenotypic Analysis and Isolation of Murine Hematopoietic Stem Cells and Lineage-committed Progenitors
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Area of Science:

  • Stem cell biology
  • Hematopoiesis
  • Cell culture optimization

Background:

  • Hematopoietic stem cells (HSCs) rapidly lose potential and differentiate ex vivo.
  • Maintaining HSC potential during ex vivo culture is critical for clinical applications like transplantation and gene therapy.

Purpose of the Study:

  • To identify culture conditions that preserve HSC potential ex vivo.
  • To investigate the effect of pH on HSC function and reconstitution ability.

Main Methods:

  • Cultivation of murine and human HSCs at pH 6.9 and pH 7.4 for 2 days.
  • Assessment of HSC characteristics including size, metabolic activity, and proliferation.
  • Evaluation of HSC reconstitution ability upon transplantation.
  • Pharmacological inhibition of the polyamine pathway using DFMO.

Main Results:

  • HSCs cultivated at pH 6.9 maintained their potential, remaining smaller, less metabolically active, and less proliferative compared to those at pH 7.4.
  • HSCs at pH 6.9 exhibited enhanced reconstitution ability after transplantation.
  • An attenuated polyamine pathway was observed in HSCs cultured at pH 6.9.
  • Pharmacological inhibition of the polyamine pathway at pH 7.4 mimicked the beneficial effects of pH 6.9.

Conclusions:

  • Ex vivo cultivation at pH 6.9 positively regulates HSC function by reducing polyamine levels.
  • This pH-dependent regulation offers a strategy to improve short-term HSC cultivation protocols for transplantation and gene therapy.
  • Targeting the polyamine pathway may enhance HSC function in vitro.