Robust Ex Vivo Expansion of Human Hematopoietic Stem Cells for Clinical and Research Use

Background & Unmet Need

• Hematopoietic stem cells (HSCs) play an essential role in promoting the lifelong production of mature blood cell lineages
• Stem cell transplantation (SCT) using donor-derived HSCs is an effective therapy to treat multiple hematological malignancies and cancers, including leukemia and myeloma
• However, current SCT methods suffer from limitations in effectively processing an adequate number of HSCs
• Additionally, present technologies are incapable of maintaining or expanding human HSCs ex vivo
• Unmet Need: There is a need for methods that effectively expand HSCs for use in SCT therapies

Technology Overview

• The Technology: Cornell inventors have identified several methods that allow for robust ex vivo expansion of HSCs for research and clinical use
• PoC Data: Human-derived HSCs cultured under hypoxic conditions (1% O2) demonstrated increased expression of CD34+ cells, a phosphoglycoprotein which is used clinically to quantify HSCs levels (see Figure 1A)
• Co-culturing HSCs with endothelial feeder cells (ECs) also increased CD34+ expression in addition to similar markers of HSC levels (CD45, iHSC), see Figure 1B
• Treating cell cultures with N-acetyl cysteine (NAC), an antioxidant that reduces cellular damage from reactive oxygen species, likewise enhances expression of markers of HSC availability (see Figure 1C)

Technology Applications

• Described methods effectively enhance HSC expansion and may increase efficacy of SCT therapies
• Methods may also be used to expand HSCs for research purposes
• Ability to maintain viable HSCs ex vivo affords ability to modify the cells (e.g., genetic manipulations)

Technology Advantages

• Multiple methods to expand HSCs may be used in isolation or in synchrony to enhance HSC expansion effects
• Described culturing conditions are easy to implement and produce robust effects on HSC expansion