Investigation of the transdifferentiation potential of human mesenchymal bone marrow stem cells (BMSC) to tumor-associated fibroblasts

Introduction Fibroblasts are involved in wound healing and the formation of the tumor stroma. During wound healing, they lead to tissue remodeling, wound contraction and production of components of the extracellular matrix. In tumors they influence the microenvironment through direct cell-cell contact and paracrine secretion of factors. The origin of fibroblasts of the tumor stroma (tumor-associated fibroblasts (TAF)) has not been clearly established. An origin from immigrated mesenchymal stem cells (MSC) is suspected. In the present study, the possible role of wound healing and tumor cell-associated paracrine-secreted factors in the transdifferentiation of MSC to TAF was evaluated.

Methods MSCs from 10 donors were incubated with wound fluid (WS) and tumor-conditioned medium (CM) from squamous cell carcinoma cells. The expression of the TAF-typical markers fibroblast activation protein (FAP), a-smooth muscle actin (a-SMA), thrombospondin-1 and tenascin-C was evaluated with rt-PCR. Moreover, immunohistochemical analysis of FAP and a-SMA was performed.

Results Under the test conditions, different effects were registered with the MSC, whereby the heterogeneity of the TAF expression pattern was also great within the test groups. There was a tendency towards an increased expression of TAF-associated markers after incubation with CM compared to WS.

Discussion Due to tumor-specific features and inter-individual characteristics, MSC and TAF are very heterogeneous cell populations. A clear identification of TAF by specific markers is therefore hardly possible. The collected data show that an increased expression of TAF-typical markers in MSC can be induced in particular by incubation with CM.

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Publication History

Article published online:
13 May 2021