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Jan 15, 2012 (Vol. 32, No. 2)

Stem Cell Applications Hasten into the Clinic

  • Improved Drug Screening

    In Japan, ReproCELL is developing human iPSC-derived cardiomyocytes, neurons, and hepatocytes for applications in drug discovery including toxicity assays and ADME testing. “We believe iPSC technology will become mainstream in drug screening in the near future,” notes Chikafumi Yokoyama, Ph.D., CEO.

    Today, immortalized cell lines are widely used in primary screening, but those cell lines lack their original functions. Primary cells, on the other hand, have diminished function, limited sources, and significant lot-to-lot variation.

    ReproCELL’s iPSCs, in contrast, “combine the advantage of immortalized cell lines and primary cells, offering “infinite in vitro expansion and functional differentiated cells, so they can be supplied infinitely from pharmaceutical companies,” Dr. Yokoyama explains.

    “The differentiated cells are especially suitable for second and third screenings, in hit-to-lead and lead-optimization stages where more predictable efficacy and adverse effects can be measured at mid-to-high throughput,” Dr. Yokoyama continues. The benefit is fewer animal tests and accelerated drug screening.

    In the industry, one of the challenges has been to improve cell quality so iPSCs are comparable to primary cells. ReproCELL has developed iPSC-derived hepatocytes that are comparable to primary cells in terms of CYP3A4 activity. Those hepatocytes are scheduled to launch this spring.

    “The differentiation efficiency is more than 90–100%. We are developing a cryopreservation system in which the activity can be maintained at a high level,” Dr. Yokoyama adds. “We have obtained positive data so far and will continue to improve the process.

    “CYP3A4 is the most important enzyme for drug metabolism,” he notes. After the initial release, ReproCELL plans to release hepatocytes at six month intervals that express other specific types of enzymes.

    Last October, ReproCELL launched a new product line of frozen, single cardiomyocyte cells, called ReproCardio2. “The frozen cells can be formed as a thin layer in 96-well plates for use in coded aperture imaging systems,” according to Dr. Yokoyama. “In addition, the single cells can be re-aggregated to be beating clusters, which are applied to MEA systems to measure the field potentials. Cardiotoxicity can be detected with tested compounds in both measurement methods.”

  • Off-the-Shelf Cells

    Presenting at the “Stem Cell Summit”, Athersys president and COO B.J. Lehmann will outline initial clinical results from the company’s MultiStem™ trials. These off-the-shelf cells can be administered by IV line, catheter, or injection, and eliminate the historical stem cell therapy issue of donor matching, he says.

    Several clinical trials are under way. One Phase II trial with Pfizer treats moderate-to-severe ulcerative colitis. “We expect top-line readouts by early 2013,” Lehmann says. A study evaluating MultiStem for ischemic stroke is also in Phase II. Additionally, “we recently completed a Phase I trial in acute myocardial infarction. It was a small study, but we saw meaningful improvement in cardiovascular function.”

    Athersys also recently completed enrollment for the repeat-dose arm of a two-arm Phase I trial for graft vs. host disease (GvHD). Top-line results from the single-dose arm of that study are encouraging, reducing the severity and incidence of GvHD. Historically, moderate-to-severe GvHD occurs in 30–50% of matched related hematopoietic stem cell transplants and 50–70% of matched unrelated donor recipients. Among Athersys’ high-dose patients, “We saw less than 10 percent GvHD,” Lehmann says.

    The cell product provides benefits from therapeutically beneficial proteins, Lehmann explains. MultiStem cells hone to the site of the injury or an activated immune response. The cells respond to the specific situation, initiating a multimodal response. According to Lehman, “MultiStem offers a new therapeutic modality, a new way of treating disease that could complement current biological and pharmaceutical approaches.”

Readers' Comments

Posted 01/16/2012 by Irv Arons

Gail, I enjoyed your article and just wanted to let you know that I have published a complete list of clinical trials underway or about to start in using stem cells in ophthalmology. (link)

I also have a similar list for gene therapy trials in ophthalmology. (link)

Irv Arons

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