For clinical applications requiring increased cell dose or multiple injections, the Nanex ex vivo stem cell expansion system can be easily adaptable.
Preliminary studies using Nanex-expanded HSCs in limb rescue showed that the mouse group injected with Nanex-expanded cells exhibited restored blood flow in the ischemic leg several fold better than freshly isolated HSCs. Arteriocyte is involved in a NIH-funded Phase I safety and feasibility clinical studies using cord blood derived Nanex-expanded HSCs for the treatment of critical limb ischemia.
Another clinical opportunity is to use Nanex-expanded cells as a more cost-effective alternative for hematopoietic stem cell transplantation (HSCT).
Initial clinical observations of decreased graft-versus-host disease following human UCB transplantation prompted greater investigation into UCB cells as an alternative source for bone marrow transplantation. A problem unique to UCB transplantation is the limited availability of original donor lymphocyte or HSCs for multiple infusions.
Recent UCB transplantation clinical studies showed that engraftment can be achieved in adult patients but is delayed compared with unrelated bone marrow due to limitation in number of HSCs infused.
Furthermore, the cell dose (either nucleated cell/kg or CD34+ cells/kg) correlated with clinical outcome in most studies. Therefore, alternative strategies have been developed to improve these outcomes such as the use of expanded, pooled, or sequential UCB-derived HSCs transplantation with nonmyeloablative or reduced intensity conditioning regimens.
Alternative strategies were often ineffective as patients developed mixed lymphocyte reaction. The Nanex-based stem cell expansion system for transplantation for hematological malignances and metabolic disorders can address these challenges and provide an attractive option for HSCT.
Arteriocyte has also been developing Nanex technology to produce packed red blood cells (RBCs), which will ultimately supply O-negative packed red cells for blood transfusion. Recent studies on the effects of blood that has been stored for longer than 14 days indicated increased risk of organ failure.
Although the available supply of both whole blood (WB)/RBCs and non-RBC components was sufficient to meet overall transfusion demands, concerns about blood supply adequacy in the U.S. remain. One of the reasons is the shrinking margin between allogenic WB/RBC supply and demand.
Recently, Arteriocyte successfully demonstrated that a total of 35 million erythrocytes can be produced from a single Nanex-expanded HSCs. This data indicates the utility of Nanex stem cell expansion technology for a large-scale production of packed erythrocytes.
Although still in the early stages of development, with a lot of technical challenges remaining to be solved, we envision a fully closed, portable automated bioreactor that can produce packed RBCs continuously. Eventually we anticipate that the large-scale production of red cells to replace blood donation will be a reality and not science fiction.
Arteriocyte’s Nanex stem cell expansion technology can advance various research and clinical opportunities in the stem cell industry. The company is actively pursuing additional applications using Nanex-expanded stem cells including cell-based drug screening and hematopoietic stem cell transplantation.