1. Scope

Keywords

Rationale

Approved treatments with hematopoietic stem cells (HSCs) approach 70,000 worldwide each year; and both HSCs and mesenchymal stem cells (MSCs) are the focus of hundreds of clinical trials evaluating both stem cell therapies and gene therapies that utilize HSCs. Previously, all of these important treatments have been administered to patients without a method to determine the specific dosage of the critical stem cells. New technologies are now available for quantifying the specific fraction or dosage of tissue stem cells, including hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). As these new methods are adopted and come into wider usage, their standardization will be important to ensure the reliability and quality of the stem cell dosage data they provide. The new tissue stem cell quantification methods require an input of cumulative population doubling data derived from the serial culture of a sample of an evaluated stem cell treatment. The accuracy and precision of the input cumulative population doubling data is crucial for the resulting accuracy and precision of the stem cell-specific dosage determinations. An ASTM standard for the overall cumulative population doubling procedure can become an essential guide for users of the new tissue stem cell quantification technology. It will assist their efforts to achieve the highest quality determinations of stem cell dosage, which is an essential critical quality attribute for effective stem cell and gene therapies. A standard for cumulative population doublings will have additional beneficial applications beyond its use for tissue stem cell quantification methods. Since Leonard Hayflick's reports in the 1960's, cumulative population doubling data have been recognized and used in in vitro cell research as a cell culture parameter for evaluation of the proliferative rate and capacity of primary vertebrate tissue cells. It is recognized as a better basis than culture passage number for comparing the proliferation of primary cells from different tissue sources, different tissue donors, and maintained with different culture media and supplements.