Size and shape of human mesenchymal stem cells may predict future biochemical behavior potentially linked to supporting bone growth
Scientists at the US Food and Drug Administration (FDA) are studying characteristics of human mesenchymal stem cells (MSC) that correlate with mineralization of MSC, which is a prerequisite step in bone formation.
Mineralization is the deposition of calcium by human mesenchymal stem cells (MSCs) that have received the appropriate stimulation. MSCs can turn into a variety of cells types, including those that form fat tissue, cartilage, or bones, depending on the stimulation. Many scientists, including those at FDA, are studying their properties for potential use for a variety of therapies aimed at restoring certain tissues in animals and humans.
However, in order to determine if MSCs are likely to have desirable properties, scientists can assess their potential to perform certain functions in laboratory tests.
In the case of MSCs being studied for use in bone repair, a commonly used test to determine if a batch of MSCs will mineralize requires the cells to be grown for 35 days in a culture after stimulation. During that time, the cells grow in number and undergo a variety of changes in function, such as the production of an enzyme called alkaline phosphatase, which helps the cell to mineralize. One way to assess MSC potential for mineralization at day 35 is to determine if it is producing alkaline phosphatase.
In contrast, the FDA scientists used rapid, automated, microscopic measurements of the size and shape of MSCs at various days after stimulation. Their findings show that it is possible to predict on day three with 92% certainty whether stimulated MSCs would undergo mineralization at day 35.
While other laboratories have used measures of size and shape to predict MSC behavior, they used cells from only small numbers of donors. The FDA technique used a larger number of donors that represented a variety of ages, both genders, and various MSC manufacturing processes.
The FDA scientists also showed that their technique can measure differences in the ability to mineralize among MSCs that have been grown for different durations in the laboratory.
The ability to rapidly predict at day three that MSCs will mineralize at day 35 could be a step to help identify MSCs that have the desired biochemical activities that would be among those needed for bone growth when used in humans. This research needs to be confirmed in additional samples and studies.
This work was done by FDA scientists in the Office of Cellular, Tissue and Gene Therapies (OCTGT).
“High Content Imaging of Early Morphological Signatures Predicts Long Term Mineralization Capacity of Human Mesenchymal Stem Cells upon Osteogenic Induction”
First published online: February 11, 2016
Ross A. Marklein, Jessica L. Lo Surdo, Ian H. Bellayr, Saniya A. Godil, Raj K. Puri, Steven R. Bauer
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug