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HemaCare Aids Strategy for Boosting Gene Therapy Efficiency

May 21, 2019 10:06:00 AM / by Nancy Andon, MSc

Lab mouse-1An independent publication cites the use of bone marrow and mobilized peripheral blood sourced from HemaCare in a study aimed at improving the efficiency of resource consumption in gene therapy.

The publication, published in the journal Molecular Therapy, focuses on the use of lentiviral vector (LV) to introduce corrected versions of defective genes into stem cells. The goal of gene therapy is to transplant these stem cells into people suffering from genetic disease, in hopes of restoring the function of the faulty gene. One of the main challenges in this clinical strategy is the cost; substantial amounts of LV are needed to modify a therapeutically effective dose of stem cells.Researchers at UCLA may have found a way around this problem. Current approaches for gene modification rely on simply isolating as many stem cells as possible. This requires using large amounts of LV to make sure enough of the stem cells incorporate the new copy of the gene. The authors reasoned that if they could modify their stem cell enrichment method to isolate the specific subset of stem cells associated with long-term engraftment, they could significantly reduce the amount of LV needed to genetically modify those cells.

Traditionally, stem cells are isolated from bone marrow or mobilized peripheral blood by “gating” on CD34+ cells during the cell sorting procedure. This means that investigators use a fluorescence tagging method known as FACS, to capture those cells displaying the CD34 protein marker that positively identifies stem cells. Most of these cells, however, have a limited post-transplant lifetime. Only 5-10% of CD34+ cells are capable of long-term engraftment.

The authors realized that if they could identify the subset of cells responsible for long term engraftment and proliferation, enriching for these specific cells during the initial isolation procedure would make the whole process much more efficient.

After obtaining bone marrow and mobilized peripheral blood tissue from healthy HemaCare donors, the scientists worked out an immunomagnetic bead (IB) strategy that positively identified CD34+/CD38- stem cells as the cell subtype linked with long-term immune cell repopulation. They were able to achieve a 12-fold enrichment of this target cell population using the new IB strategy. The UCLA-based group then followed up on this success by genetically modifying the cells via LV transfection, and transplanting them into immunodeficient mice. On their first try, the CD34+/CD38- stem cells were successfully transplanted, but resulted in delayed immune cell proliferation. By adding unmodified CD38+ cells into their transplant mixture, the group was able to re-establish normal immune cell proliferation in the mice, as well as achieve long-term engraftment that rescued immune function.

This research is very promising because the process uses 7-fold less LV to accomplish essentially the same result scientists have achieved by transplanting bulk CD34+ stem cells, rather than enriching for the CD34+/CD38- subset. While the method has so far only been tested in mice, the UCLA researchers intend to continue their research, with the hope of eventually bringing it to the clinic. 


  1. Masiuk K. E., et al. Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells. Molecular Therapy. 25(9); 2163-2175. Sep 2017.

Topics: Gene Therapy, Bone Marrow, Stem Cells

Nancy Andon, MSc

Written by Nancy Andon, MSc

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