Prediction of Mesenchymal Stromal Cell Immune Suppression Using Live Imaging in a Three-Dimensional Microfluidic...

Area of Science:

• Cell Biology
• Biomedical Engineering
• Regenerative Medicine

Background:

• Mesenchymal stromal cells (MSCs) show promise for regenerative medicine due to multipotency and immunomodulation.
• Current 2D assays struggle to predict MSC therapeutic function by not mimicking 3D tissue environments.
• MSC behavior is influenced by biochemical and biophysical cues in their microenvironment.

Purpose of the Study:

• To investigate if live imaging of MSCs in a 3D biomimetic environment can predict their immunomodulatory potency.
• To correlate dynamic MSC phenotypes with functional outcomes in a tissue-mimetic model.
• To establish advanced 3D microphysiological systems for assessing cell-based therapies.

Main Methods:

• Utilized a high-throughput 3D microfluidic device for real-time live imaging of MSCs from five donors.
• Quantified donor-specific MSC morphological features (compactness, eccentricity, solidity, extent) and migration dynamics.
• Compared 3D phenotypic data with donor-matched immunosuppressive potency measured by standard T-cell suppression assays.

Main Results:

• MSCs displayed significant donor-specific variations in morphology and migration patterns within the 3D microenvironment.
• Key 3D phenotypic features, including migration and locomotion levels, strongly correlated with immunomodulatory function.
• Donors with higher T-cell suppression capacity exhibited distinct morphological traits and enhanced migratory behaviors.

Conclusions:

• Tissue-mimetic 3D microenvironments elicit dynamic MSC phenotypes that are predictive of immunomodulatory function.
• Live imaging in 3D microphysiological models offers a superior method for assessing MSC therapeutic potential.
• This approach bridges the gap between in vitro cell behavior and functional outcomes for cell-based therapies.