International Conference onStem Cells, Regenerative Medicine and Tissue Engineering

Title: Insights on Amniotic-derived stem cell phenotype role in promoting early Tendon Regeneration

Abstract:

Statement: Tendon and ligament injuries comprise almost 50% of sports and physical activity-related defects, causing millions of new diseases annually worldwide. Acute tendon injuries determined from trauma or physical strain constitute a major clinical challenge because of the absence of therapies able to overcome the poor intrinsic healing capacity of tendons. The incomplete recovery of tissue homeostasis is responsible for the clinical scenario of chronicity impairing patient prognosis. Recent advances indicate that the grafting of exogenous or endogenous stem cell populations exerts substantial regenerative effects. Amongst them, amniotic-derived cells recently emerged as tendon pro-regenerative stem cell sources documenting efficacy either under preclinical or clinical settings (1). In particular, a xenogeneic preclinical study (human amniotic epithelial cells-hAEC transplanted in injured ovine tendons) started to define the mechanisms mediating AEC tendon healing introducing elements to improve their regenerative future use. hAEC, indeed, exerted their early healing effect by up-regulating limited transcripts (49 out of 4000 analyzed) belonging to tendon-lineage related function (epithelial-mesenchymal transition, connective specific matrix components, and skeleton or muscle system development) and paracrine signaling pathways modulating inflammatory and immunomodulatory actions (2).
Aim: The purpose of this study is to verify how the phenotype of transplanted AEC (epithelial, mesenchymal, or early tendon differentiated) affects the process of early tendon healing.
Methodology & Experimental Plan: To verify the role of the stepwise in vivo trans-differentiation of AECs during early tendon healing, in the present research 3 different AEC subsets displaying epithelial (eAECs), mesenchymal (mAECs), and tendon (tdAECs) phenotype (3-4) were allotransplanted in a validated experimental model of sheep Achilles tendon injury (5). Tissue healing was comparatively analyzed at two healing endpoints (14 and 28 days).
Results: All subsets of AEC were able to accelerate tendon healing: mAECs with a lesser extent than eAECs and tdAECs in terms of key histological tissue scores at both 14 and 28 days. Of note, eAECs and tdAECs displayed 2 different underlying regenerative mechanisms. The eAECs exerted a greater ability to convey host tissue shift from pro-inflammatory to pro-regenerative responses (immune cell presence and cytokines expression profiles), leading to a prompt and more ordered extracellular matrix (ECM) deposition and blood vessel remodeling. On the other hand, tdAECs acted mainly on the proliferative phase by impacting the density and organization of ECM (low cellularity and angle alignment).
Conclusion & Significance: AEC-based therapies are confirmed as a concrete therapeutic advanced solution to the challenges of tendon care and sector policy goals. The present evidence highlights the opportunity for differentiated and targeted use of this stem cell source to face tendinopathies. In particular, the transplantation of eAECs is a preferable strategy for the treatment of acute injuries taking account of their greater plasticity and stronger immunomodulatory properties.

Biography:

Barbara Barboni is a cell biologist from years addressed the study of reproductive-derived cells’ function. Her scientific expertise has always made use of both theoretical (systems biology) and experimental approaches in vitro and in vivo mainly on preclinical models of regeneration. She has built her university commitment after years of experience in research, evaluation, teaching, and administration in university and ministerial institutions.