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Apigenin Boosts Expansion of hematopoietic Stem Cells, Offering Potential for Improved Bone Marrow Transplantation

BOSTON, MA – A new study published in Scientific Reports on February 21, 2024, details how apigenin (AP), a naturally occurring flavonoid found in chamomile, parsley, and other plants, considerably enhances the expansion of umbilical cord blood (UCB)-derived CD34⁺ hematopoietic stem cells (HSCs) in vitro. Researchers at the brigham and Women’s Hospital, a teaching hospital of Harvard medical School, demonstrated that AP treatment increased the number of HSCs without inducing differentiation, a critical factor for triumphant bone marrow transplantation.

Background: The Promise of Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for various hematological malignancies, including leukemia, lymphoma, and myeloma, as well as certain inherited immune deficiencies. UCB is a valuable source of HSCs, offering advantages such as readily availability and reduced risk of graft-versus-host disease compared to bone marrow. though,the limited number of HSCs in a single UCB unit frequently enough restricts its use,notably for adult patients. Therefore, expanding HSCs ex vivo (outside the body) is crucial to generate sufficient cell numbers for transplantation. Current expansion methods frequently enough induce HSC differentiation, compromising their self-renewal capacity and long-term engraftment potential.

Apigenin’s Impact on HSC Expansion and Gene Expression

The study investigated the effects of 5µM apigenin on UCB-CD34⁺ cells.Results showed that AP significantly upregulated the expression of genes associated with HSC self-renewal and maintenance,including FOSL2,ITGA2B,and ITGB3. Specifically, FOSL2, a proto-oncogene, plays a role in cell proliferation and survival. ITGA2B and ITGB3 encode integrin subunits crucial for cell adhesion and signaling, vital for HSC maintenance in the bone marrow niche.

Conversely, AP significantly downregulated genes linked to cell cycle arrest and cellular senescence (ATM, SIRT1, SLC25A4), HSC activation and differentiation (ID2, BMPR1A, LDB1, TGM2, TET1, MAF, FOSL2), tumorigenesis and cancer targets (PLCG1, CACNA2D2, CDH1), and extracellular matrix (ECM) and proteoglycan components in cancer (EXT1, LUM, EPCAM). This suggests that AP dose not promote genes involved in cell differentiation or cancer development within the UCB-CD34⁺ cell population.

Implications and Future Research

These findings indicate that apigenin modulates multiple pathways essential for maintaining the self-renewal and multi-lineage differentiation capacity of HSCs. The researchers emphasize that while these results are promising, further investigation is needed to elucidate the direct effects of AP on these pathways. Specifically, they recommend utilizing specific inhibitors for each pathway to confirm AP’s mechanism of action. The study, conducted over three independent experiments, utilized Nanostring analysis to assess gene expression changes (P < 0.05). A detailed list of statistically meaningful upregulated and downregulated genes is provided in Table 2 (see original article).

This research opens avenues for developing novel ex vivo HSC expansion protocols that could improve the efficacy of HSCT, particularly for patients lacking fully matched donors. Further studies are planned to evaluate the long-term effects of apigenin treatment on HSC function and engraftment in preclinical models.

Source: scientific Reports, DOI: 10