Amniotic Membrane and Stem Cells Can Improve the Immunohistochemical Profile of Achilles Tendons in Injured Rats

Disorders of the Achilles tendon are common and have a major socio-economic impact. Current treatments (drugs, physiotherapy, and surgery) do not provide lasting relief, leading to chronicity and recurrence. In this context, experimental studies on regenerative therapies, such as stem cells, and natural and synthetic membranes, have shown promising results in the treatment of tendon lesions. <b>Background/Objectives</b>: The present study analyzes the response of tissue to a combination of bone marrow mononuclear cells (BMMCs) and human decellularized amniotic membrane (AM) for the treatment of Achilles tendon lesions in rats. <b>Methods</b>: Forty male Wistar rats were randomized into four treatment groups: SC (stem cells), AM (amniotic membrane), SC + AM (stem cells + amniotic membrane), and C (control). All underwent Achilles tendon sectioning and tenorrhaphy. In the AM and SC + AM groups, the amniotic membrane was sutured over the lesion after the tendon was sutured; in the SC and SC + AM groups, 2 mL of autologous blood from the iliac crest containing BMMCs was applied around the lesion. Animals in Group C received only 2 mL of 0.9% saline around the lesion. After four weeks, the animals were euthanized, and the tendons were sent for histological analysis (<i>Picrosirius Red</i>) and immunohistochemistry (IL-6, IL-4, and IL-13). <b>Results</b>: Analysis of type I and type III collagen fibers showed no differences between groups. However, the SC + AM group showed the highest expressions of IL-4 and IL-13. <b>Conclusions</b>: IL-4 and IL-13 are cytokines known to be associated with tissue repair and organization. This suggests that the therapy associated with SC and AM is potentially beneficial in the treatment of injured Achilles tendons. However, further studies are necessary to clarify the benefits of this treatment for the function and biomechanical properties of the tendon and prove whether this association could represent a combined Advanced Therapy Medicinal Product (cATMP). Such a product would contain SC and a biological membrane, providing a mechanical structure for the injured tendon and active biological cells. Another possible medical approach could be immunobiological drugs targeting IL-4 and IL-13.