We blogged recently about Mesenchymal Stem/Stromal Cell (MSC) Misconceptions that are holding the translational cell therapy field back, as identified by Donald Phinney and Luc Sensebé. Since we have come to market with our own hMSC product lines, we have spoken with hundreds of MSC researchers and engineers, and we have compiled our own set of misconceptions that we think build off of Dr. Phinney’s and Dr. Sensebe’s initial concept. This blog post is to share some of the market-based feedback that we have received.
To the list that was published in Cytotherapy, we would like to contribute the following list to the conversation:
1. Tracking MSC passage number is an accurate and reliable means of tracking cell age and standardizing experimental workflow
In many research laboratory environments, cellular age is most often tracked by the number of times a cell has been passaged; however, Passage Number is quite imprecise and not very acceptable as one gets into regulated environments such as translational clinical activities. It is generally accepted that tracking the Population Doubling Level (PDL) or Cumulative Population Doublings (CPD) of primary cells is a best practice on understanding cellular age in vitro. Since it is well documented that PDL impacts hMSC function (see here, here and here), in order to drive consistency into experiments, it has become a best practice to perform experiments or develop products with cells in a consistent range of population doublings where the cell function of interest is still robust. Furthermore, regulatory agencies are beginning to require reporting of PDLs, or at least cell seeding and harvest densities, for primary cells intended for therapeutic use. In an effort to drive adoption of PDL tracking and reporting, we’ve created a Best Practices Educational Powerpoint, and free, easy-to-use PDL calculator worksheet we’re happy to share with colleagues. For your copy, just email us at email@example.com or subscribe to our blog!
2. Performing experiments with one MSC donor and/or lot is adequate for publication and moving forward with pre-clinical studies
Despite indications of clinical effectiveness of MSCs, there is repeated news of the failure of high-profile MSC trials to demonstrate efficacy in a number of therapeutic applications. It has been suggested that the large amount of intra- and inter-donor variability in the MSC populations used in these trials may be responsible for their falling short of expectations despite highly encouraging in vitro and in vivo pre-clinical data. Thus, to ensure the robust production of functional MSC products over a range of applications, experiments should be conducted and systems validated with MSCs from several donors. It has been reported that best practices to qualify a manufacturing process should include “at least 3-5 donors”, and it is likely that proper Validation will require many more, and that donor selection may be required (i.e. not every donor will work in the manufacturing process). This is why we, at RoosterBio, believe in providing a number of donor MSC lots, ranging in age and sex, for use in our customer’s research and development experiments.
3. MSCs accelerate cancer…..MSCs can combat cancer