Organelles

Analyzing the
Business and Technology
of Stem Cells

Fifteen Years, 60 Companies, 196 Trials (Appendix A)

Where Commercial Stem Cell Clinical Trials Have Been, and Where They're Going: A Quantitative Analysis

September 19, 2013

Appendix A: Cell Type Nomenclature

Any analysis of stem cell clinical trials, such as this series, would be sadly incomplete without some attempt to tackle the challenge of classifying trials according to the stem cell types they employ. But this challenge is both daunting and fraught with hazard for a variety of reasons:

Faced with such widespread uncertainty and inconsistency, it is virtually certain that any effort to meaningfully classify the cell types employed across all clinical trials will meet with considerable controversy, some confusion, and even occasional disparagement. Nevertheless, we believe that the effort is both important and worthwhile. To that end we have developed a practice-based classification scheme (Figure A1), focusing on cell preparations (as opposed to cell 'types'), their source tissues and molecular markers (where this information is available), and their vendors' own assertions (moderated by reasonable skepticism where appropriate).

This classification scheme necessarily relies heavily on the language employed in trials' ClinicalTrials.gov (CTG) registration records, supplemented as needed by information from other relevant sources, including:

We have attempted to minimize our reliance upon educated guesswork, but freely admit that this effort sometimes requires just that, as well. We encourage readers to let us know where we appear to have failed, and how, by emailing their comments to trials(at)BusaConsultingLLC(dot)com.

Figure A1: Classification (by preparation) of stem cells employed in industry-sponsored clinical trials. (Click to view full-size)

The nomenclature we have adopted (Fig. A1) is, we hope, the best possible compromise between the simultaneous and sometimes conflicting goals of brevity, consistency, and specificity. Each cell preparation's brief name begins with its tissue source (A: adipose tissue; BM: bone marrow; CB: cord blood; M: menses; PB: peripheral blood; P: placental tissue; UC: umbilical cord tissue), except in the special and uniquely obvious cases of ESCs (embryonic stem cells), NSCs (neural stem cells), CDCs (cardiosphere-derived cells), and BMC (bone marrow concentrate), which forego the initial tissue-source designator.

Following the tissue-source designator is a general cell-type designator: HSC for hematopoietic stem cell (which may, in practice, include various hematopoietic progenitor cell types), MSC for mesenchymal stem cell (alternatively 'mesenchymal stromal cell'), or MNC for mixed mononuclear cells (usually from blood or bone marrow, and frequently not characterized in detail; MNCs may or may not include MSCs, HSCs, and a variety of usually unspecified differentiated cell types). Two special cell-type designators employed here are DEMNC (differentially-expanded mononuclear cells, which we use to refer to Aastrom's unique preparations), and MAPC (multipotent adult progenitor cell, which we use to refer to Athersys' unique cell preparations; note that MAPCs are, in practice, frequently considered to be either a sub-population or a progenitor of conventional mesenchymal stem cells).

Where appropriate, the cell type designator is finally followed (in parentheses) by a gene product designator such as (CD34), (CD45), (CD133), (CD49c/CD90), (STRO1), or (ALDH), indicating that the cells have been selected (usually via either flow cytometry or magnetic bead immunoprecipitation) to be positive for the indicated molecular markers. An exception to this is the terminal designator (GM), indicating that the cells have been genetically modified (transiently transfected, constitutively transduced, and/or gene-deleted).

Throughout this series of articles, when a trial involves implantation of cells differentiated in vitro from a starting stem cell preparation, we classify the trial’s cell preparation as the starting stem cell preparation. For example, Advanced Cell Technologies’ trial number NCT01469832, involving the implantation of "human embryonic stem cell derived retinal pigmented epithelial (hESC-RPE) cells," is classified by us as employing ESC.