Stem cells are produced in commercial quantities, but they fly off production lines without passing through quality control, that mainstay of commercial operations. Stems cells do have to satisfy FDA regulations, but such guidelines address only safety issues—they do not attempt to determine whether stem cells are fit for any particular purpose, such as disease study or drug development.

In the absence of quality control standards, commercially sourced stem cells may or may not meet the expectations of drug developers. For example, as substitutes for patients in pharmaceutical screening applications, they may underperform or simply fail altogether.

Dissatisfied with this state of affairs, a team of scientists at Harvard University’s Wyss Institute for Biologically Inspired Engineering has proposed a stem cell quality index. The scientists were particularly interested in stem cell-derived cardiomyocytes, but it is conceivable that their suggestions could be generalized to other kinds of differentiated cells.

According to a press release issued by Harvard, the scientists identified a set of 64 crucial parameters from more than 1,000 by which to judge stem cell-derived cardiomyocytes. The result, a “multiparametric quality assessment rubric,” promises to give scientists and pharmaceutical companies the ability to quantitatively judge and compare the value of the countless commercially available lines of stem cells.

The Harvard team described their recommendations in a paper entitled “Quality Metrics for Stem Cell-Derived Cardiac Myocytes.” In this paper, which appeared March 6 in Stem Cell Reports, the scientists described how they “chose a set of experimental measurements that provide insight into not only the expression profile of the cells, but also the morphological and functional characteristics that are intimately tied to the contractile function of cardiac tissues.”

By using these experimental measurements and isolated neonatal ventricular myocytes as thier reference phenotype, the scientists developed a quality index that, in their words, “utilizes the magnitude and variance of these measurements to provide a numeric score indicating how closely the stem cell-derived myocytes match the characteristics of the neonatal cardiac myocytes.”

In addition, the scientists used a combination of gene-expression, morphological, electrophysiological, and contractility measurements.  Doing so, the scientists said, allowed them to pinpoint specific differences in the structural and functional properties of the mESC- and miPSC-engineered tissues versus the neonate tissues. These differences may have important implications for the utility of such tissues in vitro assays.

The need for quality metrics, confided study leader Kevin Kit Parker, a Harvard Stem Cell Institute (HSTI) principal faculty member, goes back at least as far as 2009, when he and Sean P. Sheehy, a co-author and graduate student in Parker’s lab, visited a number of companies that were commercially producting stem cells. “I'd never seen a dedicated quality control department, never saw a separate effort for quality control,” recalled Parker, who added that many companies seemed to assume that it was sufficient simply to produce beating cardiac cells from stem cells, without asking any deeper questions about their functions and quality.

“We put out a call to different companies in 2010 asking for cells to start testing,” Parker continued, “some we got were so bad we couldn't even get a baseline curve on them; we couldn't even do a calibration on them.” The quality of the human stem cells was so disappointing, Parker’s team resorted to using mouse stem cells to begin its study.

While limited in their utility, the mouse stem cells allowed Parker’s group to begin setting parameters. “We could tell which cells were better, how they contracted, how they expressed certain genes,” Parker explained. “Using the more than 60 measures Sean developed”—which Parker is calling the Sheehy Index—“we can say ‘these cells are good, and these aren’t as good.” Prior to this, no one’s had a quantitative definition of what a good stem cell is.”

The importance of the quality index has been discussed by HSCI co-director Doug Melton. The index, said Melton, “provides a standard for the field to move toward reproducible tests for cell function, an important precursor to getting cells into patients or using them for drug screening.” Similar comments were offered by Brock Reeve, HSCI executive director: “The faster we can help develop reliable, reproducible standards against which cells can be tested, the faster drugs can be moved into the clinic and the manufacturing process.”

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