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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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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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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
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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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Hematopoietic Stem Cells in Type 1 Diabetes.

Ida Pastore1, Emma Assi2, Moufida Ben Nasr2,3

  • 1Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy.

Frontiers in Immunology
|July 26, 2021
PubMed
Summary

Hematopoietic stem cell (HSC) therapies show promise for type 1 diabetes (T1D). Genetically engineered HSCs offer enhanced immunomodulatory abilities, potentially leading to novel biologic treatments for T1D and other autoimmune diseases.

Keywords:
NOD mouse modelautoimmune responsegenetic modulationhematopoietic stem cellstype 1 diabetes

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Area of Science:

  • Immunology
  • Regenerative Medicine
  • Endocrinology

Background:

  • Type 1 diabetes (T1D) pathogenesis is increasingly understood, yet effective treatments remain elusive.
  • Hematopoietic stem cell (HSC) transplantation and teplizumab show early promise for T1D management.
  • The long-term efficacy and optimal use of HSCs in T1D require further investigation.

Purpose of the Study:

  • To explore the potential of hematopoietic stem cell (HSC)-based therapies for delaying or reverting type 1 diabetes (T1D).
  • To evaluate the benefits of using selected and characterized HSC subsets for improved T1D treatment.
  • To assess the translational potential of ex vivo manipulated and genetically engineered HSCs in T1D models.

Main Methods:

  • Review of clinical trials and preclinical studies involving HSCs in T1D.
  • Investigation of ex vivo HSC manipulation techniques.
  • Utilizing humanized mouse models to assess HSC efficacy and safety.
  • Analysis of immunomodulatory and trafficking properties of genetically engineered HSCs.

Main Results:

  • Clinical trials indicate beneficial effects of HSCs in T1D, though durability is pending.
  • Ex vivo manipulated HSCs demonstrate promise in murine models.
  • Humanized mouse models facilitate accelerated translational research for HSC therapies.
  • Genetic engineering can enhance HSC immunomodulatory and trafficking capabilities.

Conclusions:

  • Hematopoietic stem cell (HSC) approaches, particularly genetically engineered variants, represent a promising novel biologic therapy for type 1 diabetes (T1D).
  • Further research and clinical testing are warranted to establish the safety and efficacy of these advanced HSC therapies for T1D and other autoimmune disorders.