Human mesenchymal stromal cells (MSCs) offer great hope for the treatment of tissue degenerative and immune diseases, but their phenotypic similarity to dermal fibroblasts may hinder robust cell identification and isolation from diverse tissue harvests. To identify genetic elements that can reliably discriminate MSCs from fibroblasts, we performed comparative gene and microRNA expression profiling analyses with genome-wide oligonucleotide microarrays. When taken globally, both gene and microRNA expression profiles of MSCs were highly similar to those of fibroblasts, accounting well for their extensive phenotypic and functional overlaps. Scattered expression differences were pooled to yield an MSC-specific molecular signature, consisting of 64 genes and 21 microRNAs whose expressions were at least 10-fold and two-fold higher, respectively, in MSCs compared with fibroblasts. Genes either encoding transmembrane proteins or associated with tumors were relatively abundant in this signature. These data should provide the molecular basis not only for the discovery of novel diagnostic markers discriminating MSCs from fibroblasts, but also for further studies on MSC-specific signaling mechanisms.

Summary Mesenchymal stromal cells (MSCs) have gained widespread popularity in cell therapy, but their development into clinical products has been impeded by the scarcity of cell‐specific markers. We previously explored transcriptome and membrane proteome of MSCs, from which fibroblast activation protein α (FAP) was recognized as a prime surface marker candidate. The present study showed that FAP was constitutively expressed on MSCs, but not on other cells. FAP immunoselection yielded homogeneous MSCs from cryopreserved bone marrow (BM). These results suggest that FAP serves as a surface protein marker that can singly define MSCs from BM and possibly from other sources.

Mesenchymal stem cells (MSCs) are promising for cell therapy and regenerative medicine; but their lack of specific markers renders the cell culture at potential contamination risk with other cell types, in particular, fibroblasts. In this study, we mapped 2 differential transcriptome data of MSCs compared, one to mononuclear cells and the other to fibroblasts, onto the membrane proteome data, the analysis of which led to an identification of transmembrane 4 L6 family member 1 (TM4SF1) as a surface protein marker candidate that could discriminate MSCs simultaneously from blood cells and fibroblasts. Our analyses confirmed that TM4SF1 was abundantly expressed on MSCs but neither on other blood/tissue cells nor on fibroblasts. TM4SF1 immunoselection from bone marrow and adipose tissues yielded homogeneous cell populations that were highly similar to MSCs, in terms of morphology, immunophenotype, and differentiation potential. These findings indicate that TM4SF1 can serve as a surface protein marker which singly identifies MSCs from diverse cell sources, in particular, fibroblast-rich connective tissues.

Functional severity was a major factor associated with higher COI and lower HRQOL scores. Therefore, preventing the aggravation of functional severity is crucial for decreasing the COI and improving the HRQOL of patients with RA.