Abstract
BackgroundAmniotic epithelial cells (AEC) have potential applications in cell-based therapy. Thus far their ability to differentiate into tenocytes has not been investigated although a cell source providing a large supply of tenocytes remains a priority target of regenerative medicine in order to respond to the poor self-repair capability of adult tendons. Starting from this premise, the present research has been designed firstly to verify whether the co-culture with adult primary tenocytes could be exploited in order to induce tenogenic differentiation in AEC, as previously demonstrated in mesenchymal stem cells. Since the co-culture systems inducing cell differentiation takes advantage of specific soluble paracrine factors released by tenocytes, the research has been then addressed to study whether the co-culture could be improved by making use of the different cell populations present within tendon explants or of the high regenerative properties of fetal derived cell/tissue.Methodology/Principal FindingsFreshly isolated AEC, obtained from ovine fetuses at mid-gestation, were co-incubated with explanted tendons or primary tenocytes obtained from fetal or adult calcaneal tendons. The morphological and functional analysis indicated that AEC possessed tenogenic differentiation potential. However, only AEC exposed to fetal-derived cell/tissues developed in vitro tendon-like three dimensional structures with an expression profile of matrix (COL1 and THSB4) and mesenchymal/tendon related genes (TNM, OCN and SCXB) similar to that recorded in native ovine tendons. The tendon-like structures displayed high levels of organization as documented by the cell morphology, the newly deposited matrix enriched in COL1 and widespread expression of gap junction proteins (Connexin 32 and 43).Conclusions/SignificanceThe co-culture system improves its efficiency in promoting AEC differentiation by exploiting the inductive tenogenic soluble factors released by fetal tendon cells or explants. The co-cultural system can be proposed as a low cost and easy technique to engineer tendon for biological study and cell therapy approach.
Highlights
Tendon overuse injuries, which are referred to as tendinopathy affect millions of people in occupational and sport settings [1,2]
The present results indicate that all tendon derived samples are able to generate a favorable microenvironment for tenogenic differentiation
The present work demonstrates, for the first time, that ovine Amniotic epithelial cells (AEC) can be differentiated into tenocytes by using an appropriate co-cultural microenvironment
Summary
Tendon overuse injuries, which are referred to as tendinopathy affect millions of people in occupational and sport settings [1,2]. The mechanism involved in this failure remains still unknown, it probably resides in the high degree of differentiation of this tissue and in the low cellularity that limits the capacity of differentiated tenocytes to replicate in adult organisms [3,9] For this reason, cell-based therapy or tissue engineering were suggested as an ideal approach to support tendon healing [3,10], and to this aim several cell types have been used under preclinical settings [8]. Amniotic epithelial cells (AEC) have potential applications in cell-based therapy Far their ability to differentiate into tenocytes has not been investigated a cell source providing a large supply of tenocytes remains a priority target of regenerative medicine in order to respond to the poor self-repair capability of adult tendons. Since the co-culture systems inducing cell differentiation takes advantage of specific soluble paracrine factors released by tenocytes, the research has been addressed to study whether the co-culture could be improved by making use of the different cell populations present within tendon explants or of the high regenerative properties of fetal derived cell/tissue
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