Mesenchymal stromal cells derived from patients with systemic sclerosis exhibit intrinsic hyperresponsiveness to TGF-β1, leading to significantly increased collagen production, enhanced migration toward TGF-β1, reduced proliferative capacity, and elevated expression of contractile proteins compared to mesenchymal stromal cells from healthy individuals.

In people with systemic sclerosis, the cells that normally help repair tissue become overly sensitive to a signaling protein called TGF-β1. This causes them to produce too much scar tissue, move toward the protein more aggressively, stop multiplying, and turn into stiff, contractile cells that pull on surrounding tissue. This happens because the cells keep their TGF-β1 receptors turned on longer than normal, which overactivates internal signaling pathways that control scar production, movement, and cell shape.