Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad...

Area of Science:

• Immunology
• Regenerative Medicine
• Molecular Biology

Background:

• Macrophages in the infrapatellar fat pad (IFP) modulate knee inflammatory pathologies.
• Macrophage polarization (M1 pro-inflammatory vs. M2 anti-inflammatory) is crucial in joint disease.
• Imbalance in M1/M2 macrophage phenotypes contributes to joint inflammation initiation and progression.

Purpose of the Study:

• To investigate the effect of mesenchymal stem cell (MSC) therapy on macrophage polarization within the IFP in an acute knee inflammation model.
• To identify cellular heterogeneity and transcriptional programs in the IFP.

Main Methods:

• An acute synovial/IFP inflammation rat model was established.
• A single intra-articular injection of IFP-derived MSCs was administered.
• Single-cell RNA-sequencing was used for transcriptional profiling of isolated IFP tissue.
• Control groups included diseased rats without MSC treatment and healthy rats.

Main Results:

• Eight distinct cell populations were identified in the IFP, with myeloid cells (predominantly macrophages) showing altered proportions across groups.
• Diseased samples exhibited the lowest proportion of M2-phenotype macrophages (11.9%) compared to healthy (14.8%) and MSC-treated (19.4%) samples.
• IFP-MSC therapy alleviated inflammation by inducing a phenotypic switch of macrophages towards the M2 status.

Conclusions:

• Acute knee inflammation promotes a shift towards pro-inflammatory M1 macrophages in the IFP.
• IFP-MSC therapy effectively reverses this M1 polarization, promoting an M2 phenotype.
• Understanding IFP cellular dynamics offers potential for novel therapeutic strategies in joint diseases.