scholarly journals Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

2020 ◽  
Vol 21 (5) ◽  
pp. 1582 ◽  
Author(s):  
Enrico Ragni ◽  
Carlotta Perucca Orfei ◽  
Paola De Luca ◽  
Alessandra Colombini ◽  
Marco Viganò ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Clinical Outcomes ◽  
Stromal Vascular Fraction ◽  
Target Tissue ◽  
Inflammatory Conditions ◽  
Adipose Mesenchymal Stem Cells ◽  
Tissue Restoration ◽  
Strong Capacity

Mesenchymal stem cells (MSCs) derived from adipose tissue and used either as expanded cells or minimally manipulated cell preparations showed positive clinical outcomes in regenerative medicine approaches based on tissue restoration and inflammation control, like in osteoarthritis (OA). Recently, MSCs’ healing capacity has been ascribed to the large array of soluble factors, including soluble cytokines/chemokines and miRNAs conveyed within extracellular vesicles (EVs). Therefore, in this study, 200 secreted cytokines, chemokines and growth factors via ELISA, together with EV-embedded miRNAs via high-throughput techniques, were scored in adipose-derived MSCs (ASCs) cultivated under inflammatory conditions, mimicking OA synovial fluid. Both factors (through most abundantly expressed TIMP1, TIMP2, PLG and CTSS) and miRNAs (miR-24-3p, miR-222-3p and miR-193b-3p) suggested a strong capacity for ASCs to reduce matrix degradation activities, as those activated in OA cartilage, and switch synovial macrophages, often characterized by an M1 inflammatory polarization, towards an M2 phenotype. Moreover, the crucial importance of selecting the target tissue is discussed, showing how a focused search may greatly improve potency prediction and explain clinical outcomes. In conclusion, herein presented data shed light about the way ASCs regulate cell homeostasis and regenerative pathways in an OA-resembling environment, therefore suggesting a rationale for the use of MSC-enriched clinical products, such as stromal vascular fraction and microfragmented adipose tissue, in joint pathologies.

scholarly journals Derivation, characterization, and in vitro cell regeneration of canine white adipose tissue-derived mesenchymal stem cells obtained from a mesenteric region

2021 ◽  
Vol 82 (1) ◽  
Author(s):  
Anirban Mandal ◽  
Ajeet Kumar Jha ◽  
Dew Biswas ◽  
Shyamal Kanti Guha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Cell Regeneration ◽  
Wound Healing Assay ◽  
Chain Reaction ◽  
Polymerase Chain

Abstract Background The study was conducted to assess the characterization, differentiation, and in vitro cell regeneration potential of canine mesenteric white adipose tissue-derived mesenchymal stem cells (AD-MSCs). The tissue was harvested through surgical incision and digested with collagenase to obtain a stromal vascular fraction. Mesenchymal stem cells isolated from the stromal vascular fraction were characterized through flow cytometry and reverse transcription-polymerase chain reaction. Assessment of cell viability, in vitro cell regeneration, and cell senescence were carried out through MTT assay, wound healing assay, and β-galactosidase assay, respectively. To ascertain the trilineage differentiation potential, MSCs were stained with alizarin red for osteocytes, alcian blue for chondrocytes, and oil o red for adipocytes. In addition, differentiated cells were characterized through a reverse transcription-polymerase chain reaction. Results We observed the elongated, spindle-shaped, and fibroblast-like appearance of cells after 72 h of initial culture. Flow cytometry results showed positive expression for CD44, CD90, and negative expression for CD45 surface markers. Population doubling time was found 18–24 h for up to the fourth passage and 30±0.5 h for the fifth passage. A wound-healing assay was used to determine cell migration rate which was found 136.9 ± 4.7 μm/h. We observed long-term in vitro cell proliferation resulted in MSC senescence. Furthermore, we also found that the isolated cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Conclusions Mesenteric white adipose tissue was found to be a potential source for isolation, characterization, and differentiation of MSCs. This study might be helpful for resolving the problems regarding the paucity of information concerning the basic biology of stem cells. The large-scale use of AD-MSCs might be a remedial measure in regenerative medicine.

scholarly journals Adipose Derived-Mesenchymal Stem Cells Viability and Differentiating Features for Orthopaedic Reparative Applications: Banking of Adipose Tissue

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ilaria Roato ◽  
Daniela Alotto ◽  
Dimas Carolina Belisario ◽  
Stefania Casarin ◽  
Mara Fumagalli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Articular Cartilage ◽  
Tissue Banking ◽  
Stromal Vascular Fraction ◽  
Single Infusion ◽  
Knee Arthritis ◽  
Symptomatic Knee

Osteoarthritis is characterized by loss of articular cartilage also due to reduced chondrogenic activity of mesenchymal stem cells (MSCs) from patients. Adipose tissue is an attractive source of MSCs (ATD-MSCs), representing an effective tool for reparative medicine, particularly for treatment of osteoarthritis, due to their chondrogenic and osteogenic differentiation capability. The treatment of symptomatic knee arthritis with ATD-MSCs proved effective with a single infusion, but multiple infusions could be also more efficacious. Here we studied some crucial aspects of adipose tissue banking procedures, evaluating ATD-MSCs viability, and differentiation capability after cryopreservation, to guarantee the quality of the tissue for multiple infusions. We reported that the presence of local anesthetic during lipoaspiration negatively affects cell viability of cryopreserved adipose tissue and cell growth of ATD-MSCs in culture. We observed that DMSO guarantees a faster growth of ATD-MSCs in culture than trehalose. At last, ATD-MSCs derived from fresh and cryopreserved samples at −80°C and −196°C showed viability and differentiation ability comparable to fresh samples. These data indicate that cryopreservation of adipose tissue at −80°C and −196°C is equivalent and preserves the content of ATD-MSCs in Stromal Vascular Fraction (SVF), guaranteeing the differentiation ability of ATD-MSCs.

scholarly journals Exosomes from Gastric Cancer Suppressed Adipo-differentiation of Adipose Mesenchymal Stem Cells to Promote Cancer-associated Cachexia via miR-155/ C/EPBβ pathway

2020 ◽  
Author(s):  
Ying Liu ◽  
Dan Lin ◽  
Haiyang Zhang ◽  
Huiya Wang ◽  
Ting Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Luciferase Reporter ◽  
Differentiation Capacity ◽  
Healthy Donors ◽  
Adipose Mesenchymal Stem Cells ◽  
Polymerase Chain

Abstract BACKGROUNDCancer-associated cachexia (CAC) is defined as a multifactorial syndrome including depletion of adipose tissue and skeletal muscle. Adipose tissue wasting, as a key characteristic of CAC, occurs early and is related with poor survival. However, the influence of exosomes on adipo-differentiation in CAC remained be mysterious.METHODSOil-red staining, western blotting, and real-time polymerase chain reaction (RT-PCR) were used to investigate the adipo-differentiation capacity of A-MSCs from GC patients and healthy donors. Adipo-differentiation capacity of A-MSCs treated with exosomes from GES-1 or GC cell lines was also detected. To further explore the effects of exosomal miR-155 on adipo-differentiation in vitro, we carried out luciferase reporter assay. Finally, to evaluate the function of exosomal miR-155 in vivo, BALB/c mice were subcutaneously transplanted with SGC7901 cells transfected with lentivirus containing a miR-155 overexpressing (miR-155 OE) sequence or miR-155 shRNA (miR-155 KO) or control lentivirus(NC) to observe the change of adipo-differentiation of A-MSCs.RESULTSWe showed that miR-155 was high expressed in adipose mesenchymal stem cells (A-MSCs) isolated from GC patients, which exhibited significantly suppressed adipo-differentiation. Mechanistically, targeting C/EPBβ and suppressing C/EPBα and PPARγ by GC exosomal miR-155 was demonstrated to be involved in impairing the differentiation of A-MSCs into adipocytes. The expression of C/EPBβ C/EPBα and PPARγ were rescued through downregulating miR-155 in GC exosomes. Moreover, overexpression of miR-155 improved cancer cachexia in tumor-implanted mice, charactered by weight loss, tumor progression and low expression of C/EPBβ, C/EPBα, and PPARγ in A-MSCs as well as FABP4 in tumor-related adipose tissue. Decreasing level of miR-155 in implanted tumor blocked the anti-adipogenic effects of GC. CONCLUSIONGC exosomsal miR-155 suppressed adipo-differentiation of A-MSCs via targeting C/EPBβ of A-MSCs plays a crucial role in CAC.

scholarly journals Recent advances in bone regeneration: The role of adipose tissue-derived stromal vascular fraction and mesenchymal stem cells

2017 ◽  
Vol 3 (1) ◽  
pp. 4 ◽  
Author(s):  
Reggie Hamdy ◽  
Yasir Alabdulkarim ◽  
Bayan Ghalimah ◽  
Mohammad Al-Otaibi ◽  
HadilF Al-Jallad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Bone Regeneration ◽  
Stromal Vascular Fraction ◽  
Recent Advances

scholarly journals Mesenchymal stem cells’ homing and cardiac tissue repair

2019 ◽  
Author(s):  
Renata Szydlak
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Repair ◽  
Cardiac Tissue ◽  
Cellular Therapy ◽  
Current Knowledge ◽  
Target Tissue ◽  
Intramyocardial Injection ◽  
Inflammatory Conditions ◽  
Cardiac Disorders

Nowadays, mesenchymal stem cells (MSCs) are essential players in cellular therapy and regenerative medicine. MSCs are used to treat cardiac disorders by intramyocardial injection or injection into the bloodstream. Therefore, a premise of successful MSC-based therapy is that the cells reach the site of injury and home the damaged tissue. In response to inflammatory conditions, MSCs can potentially move into the place of injury and colonize damaged tissues, where they participate in their regeneration. This review presents the current knowledge of the mechanisms of MSCs migration and target tissue homing in the field of cardiovascular therapies.

scholarly journals Alterations in the Secretome of Clinically Relevant Preparations of Adipose-Derived Mesenchymal Stem Cells Cocultured with Hyaluronan

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Peter Succar ◽  
Edmond J. Breen ◽  
Donald Kuah ◽  
Benjamin R. Herbert
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Disease Progression ◽  
Proinflammatory Cytokines ◽  
Mechanism Of Action ◽  
Stromal Vascular Fraction ◽  
Slow Disease Progression

Osteoarthritis (OA) can be a debilitating degenerative disease and is the most common form of arthritic disease. There is a general consensus that current nonsurgical therapies are insufficient for younger OA sufferers who are not candidates for knee arthroplasties. Adipose-derived mesenchymal stem cells (MSCs) therapy for the treatment of OA can slow disease progression and lead to neocartilage formation. The mechanism of action is secretion driven. Current clinical preparations from adipose tissue for the treatment of OA include autologous stromal vascular fraction (SVF), SVF plus mature adipocytes, and culture-purified MSCs. Herein we have combined these human adipose-derived preparations with Hyaluronan (Hylan G-F 20: Synvisc)in vitroand measured alterations in cytokine profile. SVF plus mature adipocytes showed the greatest decreased in the proinflammatory cytokines IL-1β, IFN-γ, and VEGF. MCP-1 and MIP-1αdecreased substantially in the SVF preparations but not the purified MSCs. The purified MSC preparation was the only one to show increase in MIF. Overall the SVF plus mature adipocytes preparation may be most suited of all the preparations for combination with HA for the treatment of OA, based on the alterations of heavily implicated cytokines in OA disease progression. This will require further validation usingin vivomodels.

scholarly journals Proteomic Analysis Reveals Commonly Secreted Proteins of Mesenchymal Stem Cells Derived from Bone Marrow, Adipose Tissue, and Synovial Membrane to Show Potential for Cartilage Regeneration in Knee Osteoarthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yura Lee ◽  
Yo Seph Park ◽  
Na Young Choi ◽  
Yong Il Kim ◽  
Yong-Gon Koh
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cartilage Regeneration ◽  
Secreted Proteins ◽  
Paracrine Factors ◽  
Knee Oa ◽  
Bone Marrow Adipose Tissue ◽  
Inflammatory Conditions

Paracrine factors secreted by mesenchymal stem cells (MSCs) reportedly modulate inflammation and reparative processes in damaged tissues and have been explored for knee osteoarthritis (OA) therapy. Although various studies have reported the effects of paracrine factors in knee OA, it is not yet clear which paracrine factors directly affect the regeneration of damaged cartilage and which are secreted under various knee OA conditions. In this study, we cultured MSCs derived from three types of tissues and treated each type with IL-1β and TNF-α or not to obtain conditioned medium. Each conditioned medium was used to analyse the paracrine factors related to cartilage regeneration using liquid chromatography-tandem mass spectrometry. Bone marrow-, adipose tissue-, and synovial membrane-MSCs (all-MSCs) exhibited expression of 93 proteins under normal conditions and 105 proteins under inflammatory conditions. It was confirmed that the types of secreted proteins differed depending on the environmental conditions, and the proteins were validated using ELISA. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis using a list of proteins secreted by all-MSCs under each condition confirmed that the secreted proteins were closely related to cartilage repair under inflammatory conditions. Protein-protein interaction networks were confirmed to change depending on environmental differences and were found to enhance the secretion of paracrine factors related to cartilage regeneration under inflammatory conditions. In conclusion, our results demonstrated that compared with knee OA conditions, the differential expression proteins may contribute to the regeneration of damaged cartilage. In addition, the detailed information on commonly secreted proteins by all-MSCs provides a comprehensive basis for understanding the potential of paracrine factors to influence tissue repair and regeneration in knee OA.

scholarly journals Isolation of Mesenchymal Stem Cells from Adipose Tissue

2015 ◽  
Vol 7 (3) ◽  
pp. 153
Author(s):  
Harsan Harsan ◽  
Silmi Mariya ◽  
Andi Asadul Islam ◽  
Eka Julianta Wahjoepramono ◽  
Irawan Yusuf
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Adipose Stem Cells ◽  
Adipose Mesenchymal Stem Cells ◽  
Polymerase Chain ◽  
Cluster Of Differentiation ◽  
The Ideal

BACKGROUND: In searching for the best source of stem cells, researcher found adipose stem cells as one of the ideal source due to its easiness in harvesting and its potential for differentiating into other cell lineage.METHODS: We isolated stem cells from adipose tissue, cultured and confirmed its immunophenotype using polymerase chain reaction.RESULTS: Cluster of differentiation (CD)44, CD73, CD90, CD105 were expressed, which represent immunophenotype of mesenchymal stem cells. CONCLUSION: Mesenchymal stem cells can be isolated from adipose tissue. KEYWORDS: adipose, mesenchymal stem cells, isolation, immunophenotype

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