Methods to Expand and Manipulate Hematopoietic Stem and Progenitor Cells

Description:

Methods to expand and manipulate hematopoietic stem and progenitor cells

Culture strategies for cost effective, ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) with enhanced in vivo repopulating ability.

HSPCs can be used to treat over 70 types of diseases including a variety of hematological disorders through transplantation and genetic therapies. Insufficient numbers of HSPCs introduced during transplantations prolong engraftment which can limit the use of single-unit patient samples. Ex vivo expansion increases the dose of HSPCs and promotes rapid and sustained engraftment, which is critical to patient recovery and survival. Fred Hutch researchers have discovered several methodologies of generating higher numbers of HSPCs in a cost-effective manner by delaying differentiation and enhancing proliferation of HPSCs ex vivo. In one methodology, researchers activated the Notch pathway using Deltaext-IgG and inhibited the aryl hydrocarbon receptor using SR1 in cultured HSPCs. Furthermore, the team cultured HSPCs with a Notch agonist and a leukocyte immunoglobulin-like receptor B2 agonist. Both techniques significantly enhanced the generation of repopulating HSPCs compared to either reagent alone. These innovations allow for improved clinical access to HSPCs and HSPC derived products.

<ul>

<li>Ex vivo expansion of HSPCs for autologous and allogeneic transplantation</li>

<li>Generation of HSPCs for cell-based therapies</li>

</ul>

<ul>

<li>Increase stem cell dose yield from a single cord blood unit</li>

<li>Faster immune system recovery after transplantation</li>

<li>Improves the cost-effectiveness of HSPC transplantation therapies</li>

</ul>

Irwin Bernstein, MD

Clinical Research Division

Colleen Delaney, MD