Combination Agent Approach for Improved Expansion and Mobilization of Hematopoietic Stem Cells

Combined treatment of plerixafor and Flt3L better mobilize stem cells and do not exacerbate graft-versus-host disease following transplatation.

The Need

Hematopoietic stem cell transplantation (HSCT) is used in patients with hematologic malignancies resulting from irradiation and graft-versus-tumor effects. However, patients who undergone HSCT may suffer complications such as graft-versus-host disease (GVHD), infection, and relapse. The most common donor graft source over the last two decades has been G-CSF-mobilized peripheral blood stem cells. However, collection of these cells and mobilization following implant is crucial for positive results. To counter this, plerixafor, an immunostimulant, has been used to improve mobilization of hematopoietic stem cells (HSC), but this combinatory therapy is still not effective for all patients. Furthermore, this particular combination increases circulating tumor cells in some leukemia patients, so is not indicated for all needs. Therefore, a way to improve the mobilization rate, reduce the side effects of HSCT, and utilize successful stem cell therapy for all patients is essential.

The Technology

Researchers at the Ohio State University, led by Dr. Jianhua Yu, developed a method to combine both plerixafor and FMS-like tyrosine kinase 3 ligand (Flt3L), which is a stem-cell specific growth factor. When delivered together, plerixafor and FLt3L synergistically mobilized more HSC and committed progenitors than currently used combinations. Furthermore, the cells were able to enhance natural killer (NK) cell expansion, which could play a role in lowering relapse rate and suppressing GVHD.

Commercial Applications

  • Cancer cell therapeutics
  • Transplant anti-rejection therapeutics

Benefits/Advantages

  • Reduces GVHD
  • Increases hematopoietic stem cells and progenitors
  • Has better mobilization than the current methods

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