Fibroblasts versus mesenchymal stromal cells – lost identity

by Alexey Bersenev on July 16, 2016 · 1 comment

in mesenchymal

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I’ve written before about Pieman Hematti’s opinion piece on Similar identity of mesenchymal stromal cells (MSC) and fibroblasts. Recently, Hematti’s lab published results of new study, which attempted to find any phenotypic and immunological differences between fibroblasts and MSCs.

Four well-established, widely used fibroblasts cell lines from 3 different original tissues were compared with adipose tissue- and bone marrow-derived MSCs. The authors used the following series of methods to compare these 2 cell types:

  • Cell morphology in culture (microscopy)
  • Immunophenotyping by frow cytometry (basic ISCT criteria and more markers)
  • Three-lineage differentiation (adipo- chondro- osteo-)
  • Immunological: response to IFN-gamma stimulation, suppression of T-cell proliferation, macrophages activation
  • Extracellular matrix protein production (fibronectin and collagen)

The conclusion – based on all these methods, fibroblasts and MSC were absolutely indistinguishable! The authors are discussing controversies in the literature, related to discrimination of fibroblalsts and MSC, but they are coming to conclusion that all differences, described by other groups as minor as differences between MSC from different tissue sources and were found mostly in gene expression:

… it is also well known that even fibroblasts display distinct and characteristic transcriptional gene expression patterns depending on the anatomic site or origin [55,56]. Furthermore, the magnitude of the differences reported in the literature between MSCs and fibroblasts is comparable to differences reported in the literature among MSCs derived from different tissues. In studies where fibroblasts and MSCs have been reported to be different, these differences are no greater than the differences between MSCs from different tissues or between fibroblasts from different tissues [18]. Given that differences in culture conditions or derivation methodologies could affect the phenotype of these cells [57,58], it is not surprising that such differences are found in gene expression studies that compare MSCs and fibroblasts.

So, Hematti has been proposing for years that MSCs and fibroblasts “could likely represent the same cell type”. I’ve not seen any response and commentaries of “MSC guys” to Hematti’s proposal. Interestingly, the recent study, published in Stem Cells TM describes the difference between dermal fibroblasts and adipose tissue-derived MSC in their secretome. Measure of VEGF and SDF-1 is proposed as rapid method for discrimination of these 2 cell types, based on metabolism/ secretome.

{ 1 comment… read it below or add one }

Christine Wells July 25, 2016 at 10:23 pm

This is a nice review of the ambiguities between fibroblasts and MSC using standard methodologies. We recently undertook a large-scale transcriptional review of MSC and did find reproducible transcriptional differences between cultured MSC and fibroblasts. This was published in peerJ this year, https://peerj.com/articles/1845/ (see also Pubmed 27042394), and is implemented in the http://www.stemformatics.org website. Note, this transcriptional analysis doesn’t make any inferences regarding functional differences between fibroblasts and MSC, at least as far as any differentiation capacity is concerned. Nevertheless, our study did show that most of the differences in MSC attributed to tissue source could be explained by donor genotype, which is an important consideration for the next generation of functional studies. It also does suggest that cultured MSC share a common phenotype that is intermediate between a quiescent perivascular progenitor and a differentiated cell type (including fibroblast).

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