Recovery of stem cell proliferation by low intensity vibration under simulated microgravity requires LINC complex

Area of Science:

• Biomedical Engineering
• Cell Biology
• Space Medicine

Background:

• Mesenchymal stem cells (MSCs) are crucial for musculoskeletal tissue repair and renewal.
• Simulated microgravity (sMG) and spaceflight unloading reduce MSC proliferation by affecting cell structure.
• Loss of proliferation in sMG may stem from compromised cytoskeleton and contractility.

Purpose of the Study:

• To investigate if low intensity vibration (LIV) can restore the proliferative capacity of MSCs under simulated microgravity.
• To determine the role of nuclear structure and the linker of nucleoskeleton and cytoskeleton (LINC) complex in sMG-induced proliferation loss and LIV's rescue effect.

Main Methods:

• Culturing MSCs under simulated microgravity (sMG) conditions.
• Applying low intensity vibration (LIV) as an exercise mimetic.
• Assessing cell proliferation, nuclear morphology, and expression of nuclear lamina and LINC complex proteins (LaminA/C, LaminB1, Sun-2, Nesprin-2).
• Disabling LINC complex function using co-depletion of Sun-1 and Sun-2 to test LIV's efficacy.

Main Results:

• sMG significantly decreased MSC proliferation and compromised cell structure, including increased nuclear height and disorganized F-actin.
• sMG reduced the expression of nuclear proteins LaminA/C, LaminB1, Sun-2, and Nesprin-2.
• LIV application restored MSC proliferation and levels of LaminA/C and Sun-2.
• Disrupting LINC complex function abolished LIV's ability to rescue proliferation.

Conclusions:

• Simulated microgravity impairs MSC proliferation by altering nuclear structure and compromising the LINC complex.
• Low intensity vibration effectively restores proliferation in sMG-affected MSCs.
• The LINC complex is essential for LIV to rescue proliferation, highlighting its mechanosensitive role in mitigating microgravity effects.