scholarly journals Galectin-3 Knockdown Impairs Survival, Migration, and Immunomodulatory Actions of Mesenchymal Stromal Cells in a Mouse Model of Chagas Disease Cardiomyopathy

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Bruno Solano de Freitas Souza ◽  
Kátia Nunes da Silva ◽  
Daniela Nascimento Silva ◽  
Vinícius Pinto Costa Rocha ◽  
Bruno Diaz Paredes ◽  
...  
Keyword(s):  
Immune Response ◽  
Chagas Disease ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Type I ◽  
Differentiation Potential ◽  
Galectin 3

Therapies based on transplantation of mesenchymal stromal cells (MSC) hold promise for the management of inflammatory disorders. In chronic Chagas disease cardiomyopathy (CCC), caused by chronic infection with Trypanosoma cruzi, the exacerbated immune response plays a critical pathophysiological role and can be modulated by MSC. Here, we investigated the role of galectin-3 (Gal-3), a beta-galactoside-binding lectin with several actions on immune responses and repair process, on the immunomodulatory potential of MSC. Gal-3 knockdown in MSC did not affect the immunophenotype or differentiation potential. However, Gal-3 knockdown MSC showed decreased proliferation, survival, and migration. Additionally, when injected intraperitoneally into mice with CCC, Gal-3 knockdown MSC showed impaired migration in vivo. Transplantation of control MSC into mice with CCC caused a suppression of cardiac inflammation and fibrosis, reducing expression levels of CD45, TNFα, IL-1β, IL-6, IFNγ, and type I collagen. In contrast, Gal-3 knockdown MSC were unable to suppress the immune response or collagen synthesis in the hearts of mice with CCC. Finally, infection with T. cruzi demonstrated parasite survival in wild-type but not in Gal-3 knockdown MSC. These findings demonstrate that Gal-3 plays a critical role in MSC survival, proliferation, migration, and therapeutic potential in CCC.

Human Mesenchymal Stromal Cells are Mechanosensitive to Vibration Stimuli

2012 ◽  
Vol 91 (12) ◽  
pp. 1135-1140 ◽  
Author(s):  
I.S. Kim ◽  
Y.M. Song ◽  
B. Lee ◽  
S.J. Hwang
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Bone Cells ◽  
Type I ◽  
Related Factors ◽  
Matrix Mineralization ◽  
Vibration Signals ◽  
Human Mesenchymal Stromal Cells

Low-magnitude high-frequency (LMHF) vibrations have the ability to stimulate bone formation and reduce bone loss. However, the anabolic mechanisms that are mediated by vibration in human bone cells at the cellular level remain unclear. We hypothesized that human mesenchymal stromal cells (hMSCs) display direct osteoblastic responses to LMHF vibration signals. Daily exposure to vibrations increased the proliferation of hMSCs, with the highest efficiency occurring at a peak acceleration of 0.3 g and vibrations at 30 to 40 Hz. Specifically, these conditions promoted osteoblast differentiation through an increase in alkaline phosphatase activity and in vitro matrix mineralization. The effect of vibration on the expression of osteogenesis-related factors differed depending on culture method. hMSCs that underwent vibration in a monolayer culture did not exhibit any changes in the expressions of these genes, while cells in three-dimensional culture showed increased expression of type I collagen, osteoprotegerin, or VEGF, and VEGF induction appeared in 2 different hMSC lines. These results are among the first to demonstrate a dose-response effect upon LMHF stimulation, thereby demonstrating that hMSCs are mechanosensitive to LMHF vibration signals such that they could facilitate the osteogenic process.

scholarly journals High-content analysis reveals senescence of cultured canine adipose-derived mesenchymal stromal cells to be reversible with a novel immortalization approach

2020 ◽  
Author(s):  
Ana Stojiljkovic ◽  
Veronique Gaschen ◽  
Franck Forterre ◽  
Ulrich Rytz ◽  
Michael H Stoffel ◽  
...  
Keyword(s):  
Content Analysis ◽  
Regenerative Medicine ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
Human Telomerase Reverse Transcriptase ◽  
Differentiation Potential ◽  
High Content Analysis

In the last decades, the scientific community spared no effort to elucidate the therapeutic potential of mesenchymal stromal cells (MSCs). Unfortunately, in vitro cellular senescence occurring along with a loss of proliferative capacity is a major drawback in view of future therapeutic applications of these cells in the field of regenerative medicine. Even though insight into the mechanisms of replicative senescence in human medicine has evolved dramatically, knowledge about replicative senescence of canine MSCs is still scarce. Thus, we developed a high-content analysis workflow to simultaneously investigate three important characteristics of senescence in canine adipose-derived MSCs (cAD-MSCs): morphological changes, activation of the cell cycle arrest machinery and increased activity of the senescence-associated beta-galactosidase. We took advantage of this tool to demonstrate that passaging of cAD-MSCs results in the appearance of a senescence phenotype and proliferation arrest. This was partially prevented upon immortalization of these cells using a newly designed PiggyBac(TM) Transposon System, which allows for the expression of the human polycomb ring finger proto-oncogene BMI1 and the human telomerase reverse transcriptase under the same promotor. Our results indicate that cAD-MSCs immortalized with this new vector maintain their proliferation capacity and differentiation potential for a longer time than untreated cAD-MSCs. This study not only offers a workflow to investigate replicative senescence in eukaryotic cells with a high-content analysis approach but also paves the way for a rapid and effective generation of immortalized MSC lines. This promotes a better understanding of these cells in view of future applications in regenerative medicine.

scholarly journals Augmenting emergency granulopoiesis with CpG conditioned mesenchymal stromal cells in murine neutropenic sepsis

2020 ◽  
Vol 4 (19) ◽  
pp. 4965-4979 ◽  
Author(s):  
Julie Ng ◽  
Fei Guo ◽  
Anna E. Marneth ◽  
Sailaja Ghanta ◽  
Min-Young Kwon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Neutrophil Extracellular Trap ◽  
Differentiation Potential ◽  
Neutropenic Sepsis ◽  
Cpg Oligodeoxynucleotide ◽  
Increased Risk

Abstract Patients with immune deficiencies from cancers and associated treatments represent a growing population within the intensive care unit with increased risk of morbidity and mortality from sepsis. Mesenchymal stromal cells (MSCs) are an integral part of the hematopoietic niche and express toll-like receptors, making them candidate cells to sense and translate pathogenic signals into an innate immune response. In this study, we demonstrate that MSCs administered therapeutically in a murine model of radiation-associated neutropenia have dual actions to confer a survival benefit in Pseudomonas aeruginosa pneumo-sepsis that is not from improved bacterial clearance. First, MSCs augment the neutrophil response to infection, an effect that is enhanced when MSCs are preconditioned with CpG oligodeoxynucleotide, a toll-like receptor 9 agonist. Using cytometry by time of flight, we identified proliferating neutrophils (Ly6GlowKi-67+) as the main expanded cell population within the bone marrow. Further analysis revealed that CpG-MSCs expand a lineage restricted progenitor population (Lin−Sca1+C-kit+CD150−CD48+) in the bone marrow, which corresponded to a doubling in the myeloid proliferation and differentiation potential in response to infection compared with control. Despite increased neutrophils, no reduction in organ bacterial count was observed between experimental groups. However, the second effect exerted by CpG-MSCs is to attenuate organ damage, particularly in the lungs. Neutrophils obtained from irradiated mice and cocultured with CpG-MSCs had decreased neutrophil extracellular trap formation, which was associated with decreased citrullinated H3 staining in the lungs of mice given CpG-MSCs in vivo. Thus, this preclinical study provides evidence for the therapeutic potential of MSCs in neutropenic sepsis.

scholarly journals Laminin-5 and type I collagen promote adhesion and osteogenic differentiation of animal serum-free expanded human mesenchymal stromal cells

2012 ◽  
Vol 4 (4) ◽  
pp. 36 ◽  
Author(s):  
Falk Mittag ◽  
Eva-Maria Falkenberg ◽  
Alexandra Janczyk ◽  
Marco Götze ◽  
Tino Felka ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Cell Attachment ◽  
Expression Patterns ◽  
Marker Genes ◽  
Type I ◽  
Laminin 5 ◽  
Laminin 1

Mesenchymal stromal cells (MSC) are differentiation competent cells and may generate, among others, mature osteoblasts or chondrocytes<em> in vitro</em> and <em>in vivo</em>. Laminin-5 and type I collagen are important components of the extracellular matrix. They are involved in a variety of cellular and extracellular activities including cell attachment and osteogenic differentiation of MSC. MSC were isolated and expanded using media conforming good medical practice (GMP)-regulations for medical products. Cells were characterized according to the defined minimal criteria for multipotent MSC. MTT- and BrdU-assays were performed to evaluate protein-dependent (laminin-5, laminin-1, type I collagen) metabolic activity and proliferation of MSC. MSC-attachment assays were performed using protein-coated culture plates. Osteogenic differentiation of MSC was measured by protein-dependant mineralization and expression of osteogenic marker genes (osteopontin, alkaline phophatase, Runx2) after three, seven and 28 days of differentiation. Marker genes were identified using quantitative reverse-transcription polymerase chain reaction. Expansion of MSC in GMP-conforming media yielded vital cells meeting all minimal criteria for MSC. Attachment assay revealed a favorable binding of MSC to laminin-5 and type I collagen at a protein concentration of 1-5 fmol/mL. Compared to plastic, osteogenic differentiation was significantly increased by laminin-5 after 28 days of culture (P&lt;0.04). No significant differences in gene expression patterns were observed. We conclude that laminin-5 and type I collagen promote attachment, but laminin-1 and laminin-5 promote osteogenic differentiation of MSC. This may influence future clinical applications.

scholarly journals Differential Production of Cartilage ECM in 3D Agarose Constructs by Equine Articular Cartilage Progenitor Cells and Mesenchymal Stromal Cells

2020 ◽  
Vol 21 (19) ◽  
pp. 7071
Author(s):  
Stefanie Schmidt ◽  
Florencia Abinzano ◽  
Anneloes Mensinga ◽  
Jörg Teßmar ◽  
Jürgen Groll ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Progenitor Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Cell Types ◽  
Type I ◽  
Cartilage Engineering ◽  
Hypoxic Conditions

Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and MSCs when cultured in hydrogels. Therefore, in this study, we compared chondrogenic differentiation of equine ACPCs and MSCs in agarose constructs as monocultures and as zonally layered co-cultures under both normoxic and hypoxic conditions. ACPCs and MSCs exhibited distinctly differential production of the cartilaginous extracellular matrix (ECM). For ACPC constructs, markedly higher glycosaminoglycan (GAG) contents were determined by histological and quantitative biochemical evaluation, both in normoxia and hypoxia. Differential GAG production was also reflected in layered co-culture constructs. For both cell types, similar staining for type II collagen was detected. However, distinctly weaker staining for undesired type I collagen was observed in the ACPC constructs. For ACPCs, only very low alkaline phosphatase (ALP) activity, a marker of terminal differentiation, was determined, in stark contrast to what was found for MSCs. This study underscores the potential of ACPCs as a promising cell source for cartilage engineering.

scholarly journals Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Nicola Alessio ◽  
Antonietta Stellavato ◽  
Domenico Aprile ◽  
Donatella Cimini ◽  
Valentina Vassallo ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Chondrocyte Differentiation ◽  
Type I ◽  
Cell Commitment ◽  
Transplant Procedure

Mesenchymal stromal cells (MSCs) are currently used for cartilage cell therapy because of their well proven capacity to differentiate in chondrocytes. The advantage of MSC-based therapy is the possibility of producing a high number of chondrocytes for implants. The transplant procedure, however, has some limitations, since MSCs may produce non-functional chondrocytes. This limit has been challenged by cultivating MSC in media with hydrogels containing hyaluronic acid (HA), extractive chondroitin sulfate (CS), or bio-fermentative unsulphated chondroitin (BC) alone or in combination. Nevertheless, a clear study of the effect of glycosaminoglycans (GAGs) on chondrocyte differentiation is still lacking, especially for the newly obtained unsulfated chondroitin of biotechnological origin. Are these GAGs playing a role in the commitment of stem cells to chondrocyte progenitors and in the differentiation of progenitors to mature chondrocytes? Alternatively, do they have a role only in one of these biological processes? We evaluated the role of HA, CS, and – above all – BC in cell commitment and chondrocyte differentiation of MSCs by supplementing these GAGs in different phases of in vitro cultivation. Our data provided evidence that a combination of HA and CS or of HA and BC supplemented during the terminal in vitro differentiation and not during cell commitment of MSCs improved chondrocytes differentiation without the presence of fibrosis (reduced expression of Type I collagen). This result suggests that a careful evaluation of extracellular cues for chondrocyte differentiation is fundamental to obtaining a proper maturation process.

scholarly journals Mesenchymal Stromal Cells and Cutaneous Wound Healing: A Comprehensive Review of the Background, Role, and Therapeutic Potential

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Michael S. Hu ◽  
Mimi R. Borrelli ◽  
H. Peter Lorenz ◽  
Michael T. Longaker ◽  
Derrick C. Wan
Keyword(s):  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wound Repair ◽  
Therapeutic Potential ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Differentiation Potential ◽  
Cutaneous Wound ◽  
Aging Populations

Cutaneous wound repair is a highly coordinated cascade of cellular responses to injury which restores the epidermal integrity and its barrier functions. Even under optimal healing conditions, normal wound repair of adult human skin is imperfect and delayed healing and scarring are frequent occurrences. Dysregulated wound healing is a major concern for global healthcare, and, given the rise in diabetic and aging populations, this medicoeconomic disease burden will continue to rise. Therapies to reliably improve nonhealing wounds and reduce scarring are currently unavailable. Mesenchymal stromal cells (MSCs) have emerged as a powerful technique to improve skin wound healing. Their differentiation potential, ease of harvest, low immunogenicity, and integral role in native wound healing physiology make MSCs an attractive therapeutic remedy. MSCs promote cell migration, angiogenesis, epithelialization, and granulation tissue formation, which result in accelerated wound closure. MSCs encourage a regenerative, rather than fibrotic, wound healing microenvironment. Recent translational research efforts using modern bioengineering approaches have made progress in creating novel techniques for stromal cell delivery into healing wounds. This paper discusses experimental applications of various stromal cells to promote wound healing and discusses the novel methods used to increase MSC delivery and efficacy.

Cryopreserved autologous multipotent mesenchymal stromal cells in the treatment of experimental tendopathy

2014 ◽  
Vol 2 (1) ◽  
pp. 62-67
Author(s):  
N. Volkovа ◽  
M. Yukhta ◽  
R. Вlonskiy ◽  
A. Kostrub ◽  
A. Goltsev
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Type I Collagen ◽  
Autologous Bone Marrow ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Collagen Type I ◽  
Biomechanical Study ◽  
Histological Structure ◽  
Type I ◽  
Structure Strength

To date, stem cells application is one of the promising methods to treat pathologies of the musculoskeletal system.Material and methods. On the model of Achilles tendon degenerative injuries in rats (n = 60) we studied the effectiveness of local and systemic administration of cryopreserved autologous bone marrow multipotent mesenchymal stromal cells (MMSCs). We analyzed the morphology of the tissue, collagen type I content and the presence of labeled РКН-26 cells. Also the biomechanical study was performed on the 7th, 21st and 45th day after transplantation.Results. It was shown that MMSCs contribute to the activation of regenerative processes in damaged tendons that was manifested in the recovery of histological structure, strength and type I collagen content. Local method of cell administration resulted in more pronounced tendon recovery as compared to systemic method. Using РКН-26 we confirmed the presence of injected cells in damaged area within 21 days.Conclusion. The results of the study can be used for argumentation and development of methods for the treatment of degenerative and dystrophic tendon damages in clinical practice.

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