Abstract
Multipotent mesenchymal stromal cells (MSCs) are well known for their tri-lineage potential and ability to differentiate in vitro into osteogenic, chondrogenic or adipogenic lineages. By selecting appropriate conditions MSCs can also be differentiated in vitro into the myogenic lineage and are therefore a promising option for cell-based regeneration of muscle tissue such as an aged or damaged sphincter muscle. For the differentiation into the myogenic lineage there is still a need to evaluate the effects of extracellular matrix proteins such as laminins (LM) which are crucial for different stem cell types and for normal muscle function. The laminin family consists of 16 functionally different isoforms with LM-211 being the most abundant isoform of adult muscle tissues. In the sphincter tissue a strong expression of the isoforms LM-211/221, LM-411/421 and LM-511/521 can be detected in the different cell layers. Bone marrow-derived MSCs in culture, however, mainly express the isoforms LM-411 and LM-511, but not LM-211. Even after myogenic differentiation, LM-211 can hardly be detected. All laminin isoforms tested (LM-211, LM-411, LM-511 and LM-521) showed a significant inhibition of the proliferation of undifferentiated MSCs but, with the exception of LM-521, they had no influence on the proliferation of MSCs cultivated in myogenic medium. The strongest cellular adhesion of MSCs was to LM-511 and LM-521, whereas LM-211 was only a weakly-adhesive substrate for MSCs. Myogenic differentiation of MSCs even reduced the interaction with LM-211, but it did not affect the interaction with LM-511 and LM-521. Since during normal myogenesis the latter two isoforms are the major laminins surrounding developing myogenic progenitors, α5 chain-containing laminins are recommended for further improvements of myogenic differentiation protocols of MSCs into smooth muscle cells.
Highlights
Replacement of damaged or aged muscle tissue with adult human stem cells is a highly promising field in regenerative medicine for reviving tissue function [1, 2]
The most prominent staining for the laminin α2 chain was found in the smooth muscle cell layers, whereas the α4 chain was mainly found in the mucosa and the circular smooth muscle cell layer
We analyzed whether individual laminin isoforms could facilitate the myogenic differentiation process of mesenchymal stromal cells (MSCs) into smooth muscle cells
Summary
Replacement of damaged or aged muscle tissue with adult human stem cells is a highly promising field in regenerative medicine for reviving tissue function [1, 2]. Human mesenchymal stromal cells (MSCs) are multipotent adult stem cells with the capacity to differentiate in vitro into the osteogenic, chondrogenic and adipogenic lineages [3, 4]. MSCs can differentiate into the myogenic lineage, another cell type of mesodermal origin [5,6,7,8,9,10]. Stress urinary incontinence is a pathological condition characterized by the decline of muscle cells in the urethral sphincter apparatus and replacement of the myogenic cells by connective tissue cells [14]. Since MSCs are able to differentiate into various lineages of mesodermal origin, it is deemed advantageous to pre-differentiate the MSCs in vitro into the myogenic lineage, avoiding unwanted differentiation processes in the damaged tissue [3]
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