Abstract
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies.
Highlights
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bone marrow MSCs (bmMSC)), adipose tissue, and human term placenta has been proposed for various clinical purposes
The biological rational for the expectation of better responses from fetal only hPSCs (f-hPSCs) is that these cells, which originate of the chorionic plate, share and connect to the fetus’ circulation
This may explain why preparations enriched for f-hPSCs were more effective than preparations of m-hPSCs consisting of cells from maternal tissues only [206]
Summary
The definition of stem cells is not straightforward. The relevant qualities of such cells depend initially on their proliferative potential and the expectations for their transdifferentiation to mature cells of different target tissues [1]. In vitro-constructed non-vascularized 3D tissue-engineered complex tissues based on differentiated stem cells seemed to fade upon their implantation This failure derives from the lack of immediate vascularization and supply, which is an inherent basic obstacle that affects the survival and growth of the implanted cellular tissue constructs. The main current applications of different types of MSCs for therapeutic uses derive from the highly significant pro-regenerative and immune-modulatory paracrine effects [48,49,50,51,52,53,54,55] These findings diverted gradually the focus of the field of stem cells from tissue engineering to therapies based on the paracrine effects of MSCs. These findings diverted gradually the focus of the field of stem cells from tissue engineering to therapies based on the paracrine effects of MSCs In such cell therapies, the activity of the cells seemed to be less dependent on the “stemness” of the cells and their differentiation potential and was associated more with the indirect effects mediated by the secretome of the therapeutic cells [56,57,58,59,60,61]
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