New way to expand human hematopoietic stem cells
Hematopoietic stem cells (HSC) are essential to cure hematological malignancies, such as leukemia, and to correct genetic defects via bone marrow (BM) transplantation. These cells may need to be propagated for cancer treatment.
Unfortunately, the clinical use of HSC is hindered by multiple problems. The major difficulty is related to the collection of sufficient number HSC from BM or other sources. In addition, although such transplantations are routinely performed at present, a substantial number of grafts are rejected, chronic graft-versus-host disease is a concern, disease relapse is a frequent problem, and access to BM of ethnic minorities is limited. Most of these problems could be circumvented by collecting HSC from umbilical cord blood. Regrettably, only a low number of HSC can be isolated from this source and many attempts have been made to expand these cells in vitro without success.
In their publication Iftakhar-e-Khuda et al report identification of a unique subset of primitive human HSC that is vascular adhesion protein-1 (VAP-1) positive and demonstrate that the level of reactive oxygen species can be fine-tuned by inhibiting the enzymatic activity of VAP-1. High concentrations of reactive oxygen species are toxic to HSC, while low concentrations are essential for their survival, self-renewal, and expansion and this can be achieved by VAP-1 inhibitors.
Importantly, treatment with VAP-1 inhibitor facilitated the in vitro maintenance and expansion of VAP-1-expressing HSC obtained from human umbilical cords. This inhibitor has been tested in several pre-clinical settings, and no toxicity has been observed. This VAP-1 based strategy to expand human HSC in vitro represent a breakthrough in stem cell research and may facilitate the clinical application of HSC.
The article Vascular adhesion protein‑1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation was published in Cellular and Molecular Life Sciences in November. Read the full article here.