Mesenchymal Stem Cell Deformability and Implications for Microvascular Sequestration.

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Cell Mechanics

Background:

• Mesenchymal stem cells (MSCs) show promise for regenerative medicine via intra-arterial delivery.
• Understanding MSC mechanics in microvasculature is crucial for effective cell sequestration.

Purpose of the Study:

• To investigate the relationship between yield pressure (PY) and mesenchymal stem cell (MSC) size and mechanical properties.
• To determine how cell diameter (DCELL) and pore diameter (DPORE) influence MSC passage through microvessels.

Main Methods:

• Transient filtration tests were used to measure mean filtration pressure (〈PY〉) across filters with varying pore sizes (DPORE).
• Cultured MSCs' cell diameters (DCELL) were measured, exhibiting a log-normal distribution.
• The ratio λ (DCELL/DPORE) was analyzed to understand its impact on MSC clearance.

Main Results:

• Yield pressure (PY) increased exponentially with the ratio λ (DCELL/DPORE) for 1.1 ≤ λ ≤ 2.2.
• The cortical shell model accurately described PY for λ ≤ 1.56, with cortical tension τ0 = 0.99 ± 0.42 dyn/cm.
• Larger MSCs significantly contributed to mean filtration pressure (〈PY〉), and heterogeneity in cell deformability impacts sequestration.

Conclusions:

• MSC sequestration in microvasculature is dependent on cell size and mechanical properties, quantified by yield pressure (PY).
• Heterogeneity in MSC populations can lead to unpredictable sequestration, but also offers potential for optimization.
• Selecting MSC fractions based on deformability could enhance targeted delivery for tissue regeneration.