Mesenchymal Stromal Cell-Based Bone Regeneration Therapies: From Cell Transplantation and Tissue Engineering to Therapeutic Secretomes and Extracellular Vesicles

Effective bone regeneration is challenging, especially in individuals with reduced regenerative capabilities due to trauma, disease, or age. Research has focused on using mesenchymal stromal cells (MSCs) or MSC-based tissue engineering to improve bone regeneration. However, translating these methods to clinical practice is difficult due to limited knowledge of how MSCs work, as well as the costs associated with producing, regulating, and using living cells and engineered tissues. Recently, the focus has shifted towards viewing MSCs as “cell factories” that release bioactive molecules and extracellular vesicles, which have trophic and immunomodulatory effects, leading to new “cell-free” therapies.

• 1
  MSCs can be isolated from various sources, each with unique characteristics and regenerative potential, influencing the choice of cell source and manipulation techniques for specific applications.
• 2
  MSCs-based therapies have demonstrated overall safety and potential for enhanced bone healing in clinical studies, although variations in study designs and the absence of control groups limit mechanistic conclusions.
• 3
  MSC-derived secretome, either as unfractionated conditioned medium or the extracellular vesicles-enriched fraction, shows promise for bone regeneration due to its multiple signaling factors and potential for modulating the immune system and promoting tissue repair.