In early December, American Society of Hematology (ASH) meeting will take place in Orlando, FL, where clinical investigators will announce clinical trial results that will improve the standard of care in hematology, and leading researchers will preview the next generation of innovations to enter clinical trials. I am excited to learn about these technical advances in medicine at ASH, to meet researchers face-to-face, and to witness interactions with the audience, peer clinicians, and press representatives.

One event I am particularly looking forward to is the scientific session: “Genomically Engineered Stem Cells: A Brave New World for Therapeutics”. This Session consists of three presentations, with three leading researchers giving an update on their work and a review of general progress in the field. They will explore the steady progress being made in engineering human Hematopoietic Stem Cells (HSC) that will create a renaissance in clinical hematology. As these innovations become clinically feasible, they will provide safe, cost effective sources of stem cells for life-saving HSC transplants, and differentiated blood cells for transfusions. These cells may also be engineered to have new immune therapeutic functions to treat cancers, autoimmune disorders, infectious disease and rare genetic diseases.

Although transfusions and bone marrow transplants have been used for many years, there are inherent limitations in finding HLA-matched donors, getting the requisite numbers of functioning cells, detecting or avoiding infectious contaminants, limitations in storage duration and transport, and other safety issues such as Graft vs Host Disease (GVHD). Dr. Rossi, one of the research speakers, calls ex vivo expansion of transplantable HSCs “one of the ‘holy grails’ of hematology” and this session will describe some of the powerful new technical tools that will soon make it possible to expand HSCs for use in a clinical setting. They will also talk about the challenges this research faces, such as safety (causing mutations, cancer, or viral infections) and practicality (e.g., cost).

The Platelet Story

In the first segment, Mortimer Poncz, MD, from the Children’s Hospital of Philadelphia, will talk about: “Blood Cells from Pluripotent Stem Cells: the Platelet Story”. Platelet transfusions are life-saving in many clinical indications, and recently several labs have published results suggesting that they have achieved the goal of generating functional platelets from in vitro megakaryocytes. But Dr. Poncz cautions that these results are not yet clinically relevant or practical. He identifies four challenges:

  1. Embryonal Stem Cells (ESCs) or induced Pluripotent Stem Cells (iPSCs) develop only into primitive megakaryocytes in vitro.
  2. The yield from ex vivo culture of stem cells is still too low.
  3. Ex vivo grown megakaryocyte/stem cells and the platelets they produce are damaged and do not last long enough when infused into patients.
  4. Many of the in vitro particles produced are not really platelets but just cytoplasmic fragments lacking function.

Hematopoietic Stem Cells

In the second segment, “Making Hematopoietic Stem Cells: Backwards and Sideways,” Derrick J. Rossi, PhD, from Harvard University’s Boston Children’s Hospital, will talk about the critical obstacle for the potential therapeutic uses of HSCs: the current inability to maintain or expand HSCs in vitro. According to his recently released abstract, Dr. Rossi will tell us about chemical compounds he has discovered that efficiently expand HSCs from bone marrow, mobilized peripheral blood, and cord blood -- an important breakthrough in the field.

Universal Donor Cells

Finally, the third speaker in this ASH Session will be Dr. David W Russell, from the University of Washington, Seattle. Russell will review the current limitations of donor or self-derived stem cells and engineered products thereof. In his talk he will discuss the possibility of “engineering” a universal donor Pluripotent Stem Cell (PSC) that could be manufactured safely and cryopreserved indefinitely. These PSCs could then be administered as needed to multiple HLA type allogeneic recipient patients, or used as a starting point for additional gene engineering insertions of therapeutic functions (e.g., Chimeric Antigen Receptors). He will also describe the gene editing technique he developed, Adeno-Associated Viral (AAV) vectors, and their application to eliminate surface expression of both HLA class I and II molecules, which trigger immune rejection in a non-matched host.

There are potential dangers in the new gene engineering techniques.  Russell has recently published commentary on a report that sequencing studies have now implicated AAV viruses in causing human Hepatocellular Carcinoma. Retroviruses, lentiviral vectors, and other means for integrating genes into the genomes of cells used for human therapy can cause cancer if the insertion occurs at certain vulnerable transcriptional sites.  There are newer gene editing techniques, including TALENs, Zinc finger nucleases - ZFNs, and CRISPr/Cas9, that will be discussed elsewhere at the ASH meeting, which may allow more precise gene editing, to avoid the danger of mutagenic off target insertions.

After years of largely theoretical interest, many gene therapy based therapeutics will now be entering clinical trials. One important entry point will be through the gene engineering of Hematopoietic Stem Cells - HSC. This special Scientific Session and others at the upcoming ASH event gives us an appreciation of “disruptive” innovations in experimental hematology that may be arriving soon in the clinic to help our patients.


If you are planning to attend the ASH annual meeting and would like to meet with Forrest or other senior-level leaders from Quintiles or Q2 Solutions, please request a meeting.

Topics in this blog post: Clinical Trials, Genomics, Innovation