Role of the mesenchymal Stem cells in tissue repair after Prolotherapy

Prolotherapy is a controlled injury utilizing mechanical, osmotic, chemical stimuli.As the result  Activation of Mesenchymal Stem Cells (MSCs) occurs.

Injury Signals:

When tissue sustains damage, it releases a variety of signals, including cytokines, chemokines, and growth factors. These signals serve to attract MSCs to the site of injury and activate their functions.

MSCs from surrounding tissues and the bloodstream migrate to the wound site, drawn by chemotactic factors that are released during the initial inflammatory response.

Initiation of the Healing Process:

1. Hemostasis and Inflammation:  

  MSCs secreting pro-inflammatory cytokines, which help recruit neutrophils and M1 macrophages to clear debris and combat potential infections.

2. Immunomodulation:  

   MSCs begin to modulate the immune response, decreasing the levels of activated T cells, neutrophils, and macrophages. They also guide the polarization of monocytes into pro-reparative M2 macrophages.

3. Paracrine Signaling: 

  MSCs release a range of growth factors and cytokines that facilitate healing. These include vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and transforming growth factor-β (TGF-β).

Control of the Healing Process:

1. Angiogenesis:  

   MSCs promote the formation of new blood vessels by secreting pro-angiogenic factors.

2. Cell Proliferation and Migration:  

   MSCs stimulate the proliferation and migration of skin cells, such as fibroblasts and keratinocytes.

3. Extracellular Matrix (ECM) Regulation:  

MSCs participate in production and remodeling of the ECM by releasing matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). They also promote collagen and elastin production by fibroblasts.

4. Re-epithelialization:  

   MSCs enhance the migration and proliferation of keratinocytes, which is essential for wound closure.

5. Granulation Tissue Formation:  

   MSCs contribute to the development of granulation tissue, characterized by a rich collagen III matrix.

6. Anti-fibrotic Activity:  

   MSCs help prevent excessive scarring by maintaining a balance between TGF-β1 and TGF-β3.

7. Resolution of Inflammation:  

As healing progresses, MSCs continue to modulate the inflammatory response, facilitating a transition from pro-inflammatory to anti-inflammatory conditions.

Throughout the healing process, MSCs demonstrate plasticity, adapting their functions to the changing needs of the wound environment. They orchestrate the complex interplay between various cell types and signaling molecules, promoting a regenerative rather than a fibrotic healing response