Aplastic Anemia Stem Cell Therapy Development

In the majority of instances, aplastic anemia (AA) presents as an immune-mediated disease. Hematopoietic stem and progenitor cells are the target of an immunological response driven by oligoclonal expanded cytotoxic T-cells, which causes their death by apoptosis and hematopoietic failure. Currently, stem cell therapy is the most effective approach for this disease. Therefore, CD BioSciences has launched aplastic anemia stem cell therapy development services.

T-cell-mediated Destruction of the Bone Marrow

Oligoclonally increased cytotoxic T-cells cause hematopoietic progenitors to commit suicide in aplastic anemia. Colony counts in tissue culture are increased when lymphocytes from aplastic bone marrows are removed, while in vitro hematopoiesis is reduced when lymphocytes from normal bone marrow are added. The lymphocyte subset's effector cells are activated cytotoxic T cells with a Th1 phenotype that produce and secrete interferon. T-cells from aplastic anemia patients have higher levels of T-bet, a transcription factor that binds to the interferon promoter region and is essential for Th1 polarization. Nearly all patients with aplastic anemia have reduced regulatory T cells, which regulate and suppress auto-reactive T cells, upon presentation. T regulatory cells were added to a mouse model of immune-mediated marrow failure to reverse pancytopenia brought on by lymph node cell infusion.

Aplastic Anemia Signaling Pathway

• Notch-1 Signaling is a Major Stimulus in the Pathogenesis of AA
  Notch1IC, the active form of Notch1, is markedly elevated in peripheral T cells of untreated AA patients and binds to the TBX21 promoter, suggesting that Notch1 directly regulates the gene encoding T-BET. Abnormal expression of T‐BET is a major factor in the pathology of AA and plays a limited role as an IFN promoter in AA patients. By reducing Notch1IC levels, detecting Notch1 in the TBX21 promoter, decreasing T-BET expression, and indicating Notch1 signaling response to GSI during active disease, diseased cells treated with secretase inhibitors in vitro. As a result, Notch1 signaling has been discovered to be the main trigger for Th1-mediated pathogenesis in AA and may represent a new target for therapeutic interventions.
• BTK Upregulation Promotes T Cell Activation and Proliferation
  Patients with severe AA have upregulated levels of Bruton's tyrosine kinase (BTK). Following T cell receptor (TCR) activation, BTK promotes the phosphorylation of phospholipase C (PLC), triggering downstream TCR signals. Treatment with a selective BTK inhibitor can suppress AA because BTK deficiency hinders T cell activation and proliferation, improving bone marrow deficiency.
• IL-23/STAT3/IL-17 Signaling Pathway Promotes AA Development
  The pathogenesis of AA may be influenced by the IL12/STAT4/IFN signaling pathway, a crucial signaling pathway in T cell immunity. The IL-23/STAT3/IL-17 signaling pathway aids in the initiation and development of AA.

Stimulating and inhibitory factors affecting aplastic bone marrow. (Javan, M. R. et al. 2021)

Our Services

CD BioSciences offers aplastic anemia stem cell therapy development services. Hematopoietic stem cell transplantation is the most effective means of curing aplastic anemia disorders. Based on our specialized laboratory team, we can contribute to aplastic anemia stem cell therapy development.

As a pioneer in biotechnology, CD BioSciences has grown into one of the largest independent biotechnology companies in the world. CD BioSciences is committed to providing professional and efficient service to our customers around the world. If you are interested in our service, please contact us.

References

1. Neal S Young. et al. (2018). Aplastic anemia. N Engl J Med. 379(17):1643-1656.
2. Javan, M. R. et al. (2021). Aplastic anemia, cellular and molecular aspects. Cell Biology International (1).