MSCs have captivated the scientific community with their immunomodulatory properties showing great promise as therapeutics for patients suffering with immune diseases. They have continuously failed, however, to translate to a therapy, due in part to poor understanding of the underlying mechanisms that govern MSC immunomodulation. MSC morphology has been shown to be predictive of MSC immunomodulation, but the underlying mechanisms behind differing donor to donor morphological phenotypes is still unknown. Here we investigate these differences using sphingolipid metabolic activity that would allow for development of potency assessment, prediction, and possible alteration using morpholomic and lipidomic data. Our findings suggest that: 1) there is a unique membrane fingerprint between high and low immune potency MSC donors 2) it is possible to change the membrane fingerprint and 3) by doing so, an increase in MSC immune potency can be achieved. These findings have profound implications for cell manufacturing and possible solutions to the challenges facing MSC translation.