Clinical Trial of “Retro-Differentiated” Stem Cells: A Novel Way to Generate Autologous Stem Cells

London UK

One of the major limitations of stem cell transplantation is the need to overcoming allogeneic barriers. The generation of stem cells from already differentiated tissue would significantly revolutionize the area of stem cell therapeutics.

In a paper published today (Abuljadayel et al. Infusion of autologous retrodifferentiated stem cells into patients with beta-thalassemia Scientific World Journal. 2006 Oct 9;6:1278-97), the British company Tristem reported treatment of 21 beta thalassemia patients with autologous “retrodifferentiated” stem cells derived from peripheral blood.
The authors reported that patients had reduced mean blood transfusion requirements, increased mean fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. None of the patients treated developed serious adverse events.

Tristem has a very interesting method of generating hematopoietic stem cells from peripheral blood by exposing of peripheral blood cells to the antibody CR3/43 which binds the human monomorphic region of the beta chain of HLA-DP, DQ and DR. This approach, has the potential to revolutionize medicine not only in the area of hematological disorders, but also for many regenerative applications since such hematopoietic stem cells are now being postulated to have ability to differentiate into numerous cell types.

The approach of Tristem is covered in numerous patents, including US patent # 6,090,625 entitled “Method of increasing the relative number of CD34.sup.+ cells in a cell population”. This patent 1 independent claim which covers “A method of increasing the relative number of CD34.sup.+ cells in a cell population including committed cells, which method comprises: (i) contacting the cell population with an agent that operably engages said committed cells; and (ii) incubating committed cells that are engaged by said agent such that the relative number of CD34.sup.+ cells increases as a result of said engaging.” Further reading of the dependent claims leads to the understanding that the “agent” that induces retrodifferentiation is an “agent” that engages a receptor that mediates capture, recognition or presentation of an antigen at the surface of the committed cells. Further reading reveals that the receptor that the agent binds to in order to induce retrodifferentiation is actually MHC I or MHC II.