How Stem Cells Heal: The Engraftment and Regeneration Cascade Once the stem cells are placed into the damaged joint, tendon, or ligament, their biological intelligence activates immediately. They don’t just sit there—they engraft, which means they physically attach to the existing tissue architecture and begin interacting with the injured environment. Engraftment is not a passive process. It is the first of several highly coordinated biological phases that allow MSCs to assess the extent of damage, communicate with surrounding cells, and orchestrate a repair response that is uniquely tailored to the site of injury. Phase 1: Environmental Sensing and Attachment As the MSCs arrive at the target site, they detect a unique combination of distress signals:
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Low oxygen levels (hypoxia), which are common in damaged or degenerated tissues Acidic pH and elevated reactive oxygen species (ROS), both indicators of cellular stress
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Inflammatory cytokines like TNF- α and IL-6 that signal immune system activation
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These cues tell the stem cells that the environment is injured—and they respond accordingly. They attach to the extracellular matrix (ECM), which is the fibrous scaffold that gives tissues their shape and mechanical properties. Once attached, they begin to release a powerful array of therapeutic molecules.
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