MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC

Abstract

Mesenchymal stromal cells (MSC) are multipotent cells with regenerative and immune-modulatory properties. Therefore, MSC have been proposed as a potential cell-therapy for bronchiolitis obliterans syndrome (BOS). On the other hand, there are publications demonstrating that MSC might be involved in the development of BOS. Despite limited knowledge regarding the functional role of tissue-resident lung-MSC, several clinical trials have been performed using MSC, particularly bone marrow (BM)-derived MSC, for various lung diseases. We aimed to compare lung-MSC with the well-characterized BM-MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to patients without BOS. Our study show that lung-MSCs are smaller, possess a higher colony-forming capacity and have a different cytokine profile compared to BM-MSC. Utilizing gene expression profiling, 89 genes including lung-specific FOXF1 and HOXB5 were found to be significantly different between BM-MSC and lung-MSC. No significant differences in cytokine secretion or gene expression were found between MSC isolated from BOS patients compared recipients without BOS. These data demonstrate that lung-resident MSC possess lung-specific properties. Furthermore, these results show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype compared to MSC isolated from good outcome recipients.

Serum‐free human MSC medium supports consistency in human but not in equine adipose‐derived multipotent mesenchymal stromal cell culture

“…Regarding their surface marker phenotype, human MSC cultured in serum‐free medium displayed a homogeneous marker expression profile according to the definition proposed by the ISCT , corresponding to previously published results on human bone marrow MSCs cultured in MACS medium . This was true for both human digMACS II MSCs, which had been raised in FBS‐supplemented DMEM during primary culture, as well as for human exMACS II MSCs, the primary culture of which had been accomplished in serum‐free medium.…”

“…Considering the inconsistent results obtained with equine samples cultured in MACS/MACS II medium, it should be acknowledged that this medium was optimized for serum‐ and xeno‐free culturing of human MSCs, at which favorable results were obtained in the current and previous studies . With respect to its use for equine MSCs, while the medium composition is undisclosed, it can be assumed that it includes components which are xenogeneic to equine cells, which might alter the cellular response.…”

“…Regarding proliferation and differentiation, ++ indicates superior results compared to control MSC cultured in FBS‐supplemented medium and + indicates either similar results as obtained in control MSC cultured in FBS‐supplemented medium or that proliferation was considered good but no control MSC were used for comparison. Regarding the immunophenotype, data are presented as in the respective studies if percentages of positive cells were presented in tables (if more than two samples were assessed, data are presented as mean ± SD or mean ± SEM ) or summarized as + for high percentage of positive cells as depicted in bar graphs or histograms or referred to as positive in the text and as – for no or low percentage of positive cells as depicted in bar graphs or histograms or referred to as negative in the text.…”

Stereological assessment of the blood‐air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non‐heart‐beating donor model for lung transplantation

“…Lung‐resident MSCs derived from adult lungs exhibited different gene expression, surface marker and cytokine expression profiles as well as different morphology and proliferative capacity compared with bone‐marrow‐derived MSCs (Rolandsson Enes et al. ). Thus, MSCs derived from other sources than bone marrow might induce differential pulmonary reactivity.…”

Surgical Model of in Vivo Culture of Stem Cells by Implantation of Fetal Organs into Adult Animals

“…They are low cost and simple execution. They are not exclusive: a lot of foetal organs was not tested here such as brain, kidney, lung, and other implantation sites are also possible, many of them having been mentioned in literature [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Our studies have many common features with organoid creation studies, except that the last are started in vitro and their growth can be obtained from other organs of the same embryonic sheet (for instance intestine crypt cells can give growth to pancreas) by experimental monitoring means [32].…”