Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate along different pathways including chondrogenic, osteogenic and adipogenic lineages. MSCs with a fibroblast-like morphology have been identified in human fetal lung. However, their frequency and characterization in human adult lung have not been yet evaluated. Therefore, we analyzed the mesenchymal phenotype and differentiation ability of cultured human adult bronchial fibroblast-like cells (Br) in comparison with those of mesenchymal cell progenitors isolated from fetal lung (ICIG7) and adult bone marrow (BM212) tissues. Surface immunophenotyping by flow cytometry revealed a similar expression pattern of antigens characteristic of marrow-derived MSCs, including CD34 (-), CD45 (-), CD90/Thy-1 (+), CD73/SH3, SH4 (+), CD105/SH2 (+) and CD166/ALCAM (+) in Br, ICIG7 and BM212 cells. There was one exception, STRO-1 antigen, which was only weakly expressed in Br cells. Analysis of cytoskeleton and matrix composition by immunostaining showed that lung and marrow-derived cells homogeneously expressed vimentin and nestin proteins in intermediate filaments while they were all devoid of epithelial cytokeratins. Additionally, alpha-smooth muscle actin was also present in microfilaments of a low number of cells. All cell types predominantly produced collagen and fibronectin extracellular matrix as evidenced by staining with the monoclonal antibodies to collagen prolyl 4-hydroxylase and fibronectin isoforms containing the extradomain (ED)-A together with ED-B in ICIG7 cells. Br cells similarly to fetal lung and marrow fibroblasts were able to differentiate along the three adipogenic, osteogenic and chondrogenic mesenchymal pathways when cultured under appropriate inducible conditions. Altogether, these data indicate that MSCs are present in human adult lung. They may be actively involved in lung tissue repair under physiological and pathological circumstances.

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

“…Over the last several years MSCs have been derived from a variety of other tissues of adult [5][6][7] or fetal origin [8,9]. Interestingly, these MSCs have also been shown to have a wider differentiation capability in vitro and in vivo than previously appreciated, at least in some experimental models, [10][11][12] and thus have attracted attention as very desirable cells for regenerative medicine.…”

The CD271 expression could be alone for establisher phenotypic marker in Bone Marrow derived mesenchymal stem cells.

“…To date, only a few markers have been developed and proved suitable for the isolation of MSCs from primary tissues. Markers that meet established criteria for their positive selection include STRO-1, CD73, CD105 and CD271, whereas CD45 and CD235 (glycophorin A) are used for the negative selection of MSCs [6,[18][19][20][21][22]. The International Society for Cellular Therapy (ISCT) proposed three minimal criteria for defining MSCs: 1) these cell population must be plastic-adherent when maintained in standard culture conditions using tissue culture flasks; 2) ≥95% of the MSCs population must express CD105, CD73 and CD90, as measured by flow cytometry and lack expression (≤52% positive) of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA class II; and 3) MSCs must be able to differentiate to osteoblasts, adipocytes and chondroblasts under standard in vitro differentiating conditions [23,24].…”

Stem Cell Therapy: an Adjunct in the Treatment of MDR Tuberculosis

“…Bone-marrow derived MSCs represent a mixture of different MSC populations and had been shown to be true for MSC from lung tissue [12]. Sabatini et al [13] showed that a plastic adherent cell population exists in human lungs isolated via BAL [14], or via tissue digestion [15]. These cells are either long-lived or not mutually exclusive and have the capacity for renewal.…”