Brain Endothelium for Expanding Hematopoietic Stem Cells

Baltimore, MD -

Expansion of human hematopoietic stem cells in the absence of differentiation would allow for development of autologous bone marrow transplants in a safe and reproducible manner. The problem is that to date, no protocol for expanding human hematopoietic stem cells has really been able to translate properly into the clinic.

In a recent paper (Cheng X et al. Human brain endothelial cells (HUBEC) promote SCID repopulating cell expansion through direct contact. Growth Factors. 2007 Jun;25(3):141-50) the use of human brain endothelial cells to grow hematopoietic stem cells was evaluated.

The investigators demonstrated that expansion of CD34 cells was possible only when the cells were co-cultured with the brain endothelial cells under conditions that allowed for cellular contact. Expansion was seen in terms of both CD34+ cell numbers, but more importantly in terms of increased ability to repopulate severe combined immunodeficient mice. A possible molecular mechanism is that the contact dependent co-culture seemed to induce expression of Wnt3 in the endothelial cells.

This study is very interesting since a previous study (Chute et al. Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38- cells and SCID-repopulating cells.Blood. 2005 Jan 15;105(2):576-83) demonstrated that human brain endothelial cells secrete soluble factors and do not require contact with the CD34 cells in order to provide expansion signals.