scholarly journals Gli1+ mesenchymal stromal cells modulate epithelial metaplasia in lung fibrosis

2019 ◽  
Author(s):  
Monica Cassandras ◽  
Chaoqun Wang ◽  
Jaymin Kathiriya ◽  
Tatsuya Tsukui ◽  
Peri Matatia ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Hedgehog Signaling ◽  
List Type ◽  
Basal Cells ◽  
Human Lungs ◽  
Metaplastic Epithelium ◽  
Organ Fibrosis

AbstractOrgan fibrosis is often accompanied by aberrant epithelial reprogramming, culminating in a transformed barrier composed of scar and metaplastic epithelium. Understanding how the scar promotes an abnormal epithelial response could better inform strategies to reverse the fibrotic damage. Here we show that Gli1+ mesenchymal stromal cells (MSCs), previously shown to contribute to myofibroblasts in the scar, promote metaplastic differentiation of airway progenitors into KRT5+ basal cells in vitro and in vivo. During fibrotic repair, Gli1+ MSCs integrate hedgehog activation to promote metaplastic KRT5 differentiation by upregulating BMP antagonism in the progenitor niche. Restoring the balance towards BMP activation attenuated metaplastic KRT5+ differentiation while promoting adaptive alveolar differentiation. Finally, fibrotic human lungs demonstrate altered BMP activation in the metaplastic epithelium. These findings show that Gli1+ MSCs integrate hedgehog signaling as a rheostat to control BMP activation in the progenitor niche to determine regenerative outcome in fibrosis.HighlightsGli1+ MSCs are required for metaplastic airway progenitor differentiation into KRT5+ basal cells.Hedgehog activation of MSCs promotes KRT5 differentiation of airway progenitors by suppressing BMP activation.Restoring BMP activation attenuates metaplastic KRT5 differentiationMetaplastic KRT5+ basal cells in human fibrotic lungs demonstrate altered BMP activation.

871 In vitro immunoregulatory effect from cervical cancer derived mesenchymal stromal cells over molecules expression in monocyte derived macrophage polarization

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A923-A923
Author(s):  
Víctor Cortés-Morales ◽  
Juan Montesinos ◽  
Luis Chávez-Sánchez ◽  
Sandra Espíndola-Garibay ◽  
Alberto Monroy-García ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Induction Medium ◽  
M2 Macrophage ◽  
List Type ◽  
M2 Phenotype

BackgroundMacrophages are immunological cells that sense microenvironmental signals that may result in the polarized expression of either proinflammatory (M1) or anti-inflammatory (M2) phenotype.1 Macrophages M2 are present in tumoral microenvironment and their presence in patients with cervical cancer (CeCa) is related with less survival.2Mesenchymal Stromal Cells (MSCs) are also present in tumor microenvironment of cervical cancer (CeCa-MSC), which have shown immunoregulatory effects over CD8 T cells, decreasing their cytotoxic effect against tumoral cells.3 Interestingly, MSCs from bone marrow (BM-MSC) decrease M1 and increase M2 macrophage polarization in an in vitro coculture system.4 Macrophages and MSCs are present in microenvironment of cervical cancer, however it is unknown if MSCs play a role in macrophage polarization. In the present study, we have evaluated the immunoregulatory capacity of CeCa-MSCs to induce macrophage polarization.MethodsCD14 monocytes were isolated from peripheral blood and cultivated in the absence or presence of MSCs from BM, normal cervix (NCx) and CeCa. Two culture conditions were included, in the presence of induction medium to favors M1 (GM-CSF, LPS and IFNg) or M2 (M-CSF, IL-4 and IL-13) macrophage polarization. M1 (HLA-DR, CD80, CD86 and IFNg) or M2 (CD14, CD163, CD206, IDO and IL-10) macrophage molecular markers were evaluated by flow cytometry. Finally, we evaluated concentration of IL-10 and TNFa in conditioned medium form all coculture conditions.ResultsWe observed that CeCa-MSCs and BM-MSCs in presence of M1 induction medium, decreased M1 macrophage markers (HLA-II, CD80, CD86 and IFNg), and increase the expression of CD14 (M2 macrophage marker). Interestingly, in presence of M2 induction medium, BM-MSCs and CaCe-MSCs but not CxN-MSC increased CD163, CD206, IDO and IL-10 (M2 macrophage markers). We observed a decreased concentration of TNFa in the supernatant medium from all cocultures with MSCs, but only in presence of CeCa-MSCs, increased IL-10 concentration was detected in such cocultures.ConclusionsIn contrast to NCx-MSCs, CeCa-MSCs similarly to BM-MSCs have in vitro capacity to decrease M1 and increase M2 macrophage phenotype.AcknowledgementsAcknowledgments The authors are indebted to gratefully acknowledge to CONACYT (Grant No. 272793) and IMSS (Grant no. 1731) for support to Juan J. Montesinos research.ReferencesMartinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014;6-13.Petrillo M, Zannoni GF, Martinelli E, et al. Polarization of tumor-associated macrophages toward M2 phenotype correlates with poor response to chemoradiation and reduced survival in patients with locally advanced cervical cancer. PLoS One 2015;10: e0136654.Montesinos JJ, Mora-García Mde L, et al. In vitro evidence of the presence of mesenchymal stromal cells in cervical cancer and their role in protecting cancer cells from cytotoxic T cell activity. Stem Cells Dev 2013;22:2508-2519.Vasandan AB, Jahnavi S, Shashank C. Human mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE 2-dependent mechanism. Sci Rep 2016;6:38308.

scholarly journals Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 403
Author(s):  
Girolamo Di Maio ◽  
Nicola Alessio ◽  
Ibrahim Halil Demirsoy ◽  
Gianfranco Peluso ◽  
Silverio Perrotta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
White Adipocyte ◽  
Drug Candidates ◽  
Fat Depots ◽  
Treatment Of Obesity ◽  
White Fat

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

scholarly journals Effect of extracorporeal shock wave therapy on equine umbilical cord blood mesenchymal stromal cells in vitro

2020 ◽  
Author(s):  
Ramés Salcedo-Jiménez ◽  
Judith Koenig ◽  
Olivia Lee ◽  
Thomas W.G. Gibson ◽  
Pavneesh Madan ◽  
...  
Keyword(s):  
Shock Wave ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Extracorporeal Shock Wave ◽  
Immunomodulatory Properties

AbstractExtracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells and decrease inflammatory and immune-reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation towards the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro

Biomaterials ◽  
2016 ◽  
Vol 98 ◽  
pp. 31-40 ◽  
Author(s):  
Anastasia Rakow ◽  
Janosch Schoon ◽  
Anke Dienelt ◽  
Thilo John ◽  
Martin Textor ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Hip Endoprosthesis ◽  
Metal On Metal

scholarly journals Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Winifred Broekman ◽  
Padmini P S J Khedoe ◽  
Koen Schepers ◽  
Helene Roelofs ◽  
Jan Stolk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Novel Therapy ◽  
Model Studies

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

Δημιουργία, in vitro πολλαπλασιασμός και διαφοροποίηση ανθρώπινων επαγόμενων πολυδύναμων βλαστοκυττάρων

2016 ◽  
Author(s):  
Ιωάννα Βαρελά
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Pluripotent Stem Cells ◽  
Rt Pcr ◽  
Induced Pluripotent

Η ανακάλυψη της μεθόδου του κυτταρικού επαναπρογραμματισμού ανθρώπινων δερματικών ινοβλαστών σε επαγόμενα πολυδύναμα βλαστοκύτταρα (induced pluripotent stem cells, iPSCs) το 2007 άνοιξε το δρόμο για τη μελέτη και την εξατομικευμένη θεραπεία πολλών χρόνιων νόσων. Επιδιώξαμε να δημιουργήσουμε iPS - κυτταρικές σειρές επαναπρογραμματίζοντας μεσεγχυματικά στρωματικά κύτταρα (mesenchymal stromal cells, MSCs) μυελού των οστών, μέσω μιας μεθόδου επαναπρογραμματισμού χωρίς ενσωμάτωση γονιδίων στο γενετικό υλικό των κυττάρων. Δερματικοί ινοβλάστες από φυσιολογικούς δότες και μεσεγχυματικά στρωματικά κύτταρα μυελού των οστών από φυσιολογικό δότη μεταμόσχευσης μυελού των οστών και από ασθενή με β-Μεσογειακή αναιμία (β-ΜΑ) διαμολύνθηκαν, μέσω λιποσωματικών φορέων, με συνθετικά mRNA που κωδικοποιούν τους μεταγραφικούς παράγοντες Oct4, Klf4, Sox2, Lin28, c-Myc. Στη συνέχεια, τα κύτταρα ελέγχθηκαν σε καλλιέργειες για τον σχηματισμό αποικιών πολυδύναμων βλαστοκυττάρων. Οι αποικίες απομονώθηκαν και με συνεχείς ανακαλλιέργειες δημιουργήθηκαν κυτταρικές σειρές, οι οποίες εξετάστηκαν για την πολυδυναμία τους με μεθόδους ανίχνευσης της έκφρασης των μεταγραφικών παραγόντων πολυδυναμίας (κυτταρομετρία ροής, RT-PCR, μελέτη του μεταγραφώματος με RNA μικροσυστοιχίες). Ως θετικός μάρτυρας και μέτρο σύγκρισης χρησιμοποιήθηκε πολύ καλά χαρακτηρισμένη εμβρυονική σειρά πολυδύναμων βλαστοκυττάρων. Οι iPS-κυτταρικές σειρές μελετήθηκαν, επίσης, ως προς τη λειτουργική τους πολυδυναμία με τον έλεγχο της ικανότητας τους να δημιουργούν in vitro εμβρυϊκά σωματίδια και in vivo τερατώματα μετά από υποδόρια εμφύτευση τους σε ανοσοανεπαρκείς ποντικούς, και ως προς τη δυνατότητα διαφοροποίησής τους σε αιμοποιητικά προγονικά κύτταρα. Η γενετική σταθερότητα των κυτταρικών σειρών ελέγχθηκε με DNA μικροσυστοιχίες συγκριτικού γονιδιωματικού υβριδισμού (aCGH). Απομονώθηκαν 3 iPS κυτταρικές σειρές από κάθε δείγμα κυττάρων, οι οποίες εμφανίζουν μεταγράφωμα πανομοιότυπο με εκείνο των πολυδύναμων εμβρυονικών βλαστοκυττάρων και. δημιουργούν εμβρυϊκά σωματίδια in vitro και τερατώματα in vivo, τα οποία αποτελούνται από ιστούς καταγωγής και από τα τρία βλαστικά δέρματα. Τα iPSCs των κυτταρικών σειρών πολλαπλασιάζονται για μεγάλο χρονικό διάστημα χωρίς μορφολογικές ενδείξες διαφοροποίησης. Με τη μέθοδο aCGH, στις iPS κυτταρικές σειρές μετά την 10η ανακαλλιέργεια ανιχνεύθηκαν πολυμορφισμοί στον αριθμό αντιγράφων (CNVs), τα οποία ήταν ελλείμματα μεγέθους περίπου 3 Mb. Η διαφοροποίηση των iPSCs σε αιμοποιητικά προγονικά κύτταρα οδήγησε στην παραγωγή CD34+ κυττάρων σε ποσοστό 8-10% των παραχθέντων κυττάρων με ασθενούς έντασης συνέκφραση του CD45, προσομοιάζοντας στο αιμαγγειακό στελεχιαίο κύτταρο. Στην παρούσα διατριβή παρουσιάζεται, για πρώτη φορά στην Ελλάδα, εξ όσων γνωρίζουμε, η τεχνολογία παραγωγής ανθρώπινων iPSCs με μια ασφαλή και αξιόπιστη μέθοδο. Οι iPSCs-κυτταρικές σειρές μπορεί να χρησιμοποιηθούν στη μελέτη ασθενειών, στον έλεγχο φαρμάκων και στην ανάπτυξη πρωτοκόλλων ιστικής μηχανικής και κυτταρικής θεραπείας.

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