scholarly journals Response of Human Mesenchymal Stromal Cells from Periodontal Tissue to LPS Depends on the Purity but Not on the LPS Source

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Setareh Younes Abhari ◽  
Christoph Koch ◽  
Johannes Gahn ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Structural Difference ◽  
Induced Response ◽  
Periodontal Tissue ◽  
E Coli ◽  
Lps Challenge ◽  
Significant Difference ◽  
Toll Like Receptor 2 ◽  
Structure Versus

Human periodontal ligament stromal cells (hPDLSCs) and gingival mesenchymal stromal cells (hGMSCs) are resident mesenchymal stromal cells (MSCs) of the periodontal tissue. The lipopolysaccharide (LPS) from Porphyromonas gingivalis is structurally distinct from that of other Gram-negative bacteria, and earlier studies linked this structural difference to a distinct virulence activity and the ability to activate toll-like receptor 2 (TLR-2), besides TLR-4 as commonly occurring upon LPS challenge. Later studies, in contrast, argue that TLR-2 activation by P. gingivalis LPS is due to lipoprotein contamination. In the present study, we aimed to define the influence of structure versus purity of P. gingivalis LPS on the immune response of hPDLSCs and hGMSCs. Cells were stimulated with commercially available “standard” P. gingivalis LPS, “ultrapure” P. gingivalis LPS, or “ultrapure” Escherichia coli LPS, and the expression of interleukin- (IL-) 8, IL-6, monocyte chemoattractant protein- (MCP-) 1, TLR-2, and TLR-4 was evaluated. The contribution of TLR-4 to the LPS-induced response was assessed using the specific TLR-4 inhibitor TAK-242. “Standard” P. gingivalis LPS induced significantly higher IL-8, IL-6, and MCP-1 production compared to the “ultrapure” LPS preparations, with no significant difference detectable for “ultrapure” LPS from P. gingivalis and E. coli. By using TAK-242, the response of hPDLSCs and hGMSCs to “ultrapure” LPS preparations was effectively inhibited to the levels comparable to those of nonstimulated controls. In contrast, high levels of response to “standard” LPS were observed, even in the presence of TAK-242. Our data show that the response of MSCs from periodontal tissue to LPS depends more on the purity of the LPS preparation than on the LPS source. Even a small amount of contaminating lipoproteins can drastically enhance the hPDLSCs’ and hGMSCs; responsiveness to P. gingivalis LPS, which might also contribute to the progression of periodontal disease.

scholarly journals The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yiqin Zhou ◽  
Haobo Li ◽  
Dong Xiang ◽  
Jiahua Shao ◽  
Qiwei Fu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Knee Arthroscopy ◽  
Infrapatellar Fat Pad ◽  
Control Group ◽  
Knee Cartilage ◽  
Fat Pad ◽  
Group 12 ◽  
Significant Difference

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

Comparative Analysis of Biological and Functional Properties of Bone Marrow Mesenchymal Stromal Cells Expanded in Media with Different Platelet Lysate Content

2018 ◽  
Vol 205 (4) ◽  
pp. 226-239 ◽  
Author(s):  
Marijana Skific ◽  
Mirna Golemovic ◽  
Kristina Crkvenac-Gornik ◽  
Radovan Vrhovac ◽  
Branka Golubic Cepulic
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immunological Tolerance ◽  
Biological Properties ◽  
Platelet Lysate ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Significant Difference

Due to their ability to induce immunological tolerance in the recipient, mesenchymal stromal cells (MSCs) have been utilized in the treatment of various hematological and immune- and inflammation-mediated diseases. The clinical application of MSCs implies prior in vitro expansion that usually includes the use of fetal bovine serum (FBS). The present study evaluated the effect of different platelet lysate (PL) media content on the biological properties of MSCs. MSCs were isolated from the bone marrow of 13 healthy individuals and subsequently expanded in three different culture conditions (10% PL, 5% PL, 10% FBS) during 4 passages. The cells cultured in different conditions had comparable immunophenotype, clonogenic potential, and differentiation capacity. However, MSC growth was significantly enhanced in the presence of PL. Cultures supplemented with 10% PL had a higher number of cumulative population doublings in all passages when compared to the 5% PL condition (p < 0.03). Such a difference was also observed when 10% PL and 10% FBS conditions were compared (p < 0.005). A statistically significant difference in population doubling time was determined only between the 10% PL and 10% FBS conditions (p < 0.005). Furthermore, MSCs cultured in 10% PL were able to cause a 66.9% reduction of mitogen-induced lymphocyte proliferation. Three chromosome aberrations were detected in PL conditions. Since two changes occurred in the same do nor, it is possible they were donor dependent rather than caused by the culture condition. These findings demonstrate that a 10% PL condition enables a higher yield of MSCs within a shorter time without altering MSC properties, and should be favored over the 5% PL condition.

scholarly journals Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat

Thorax ◽  
2015 ◽  
Vol 70 (7) ◽  
pp. 625-635 ◽  
Author(s):  
J. Devaney ◽  
S. Horie ◽  
C. Masterson ◽  
S. Elliman ◽  
F. Barry ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
E Coli ◽  
Human Mesenchymal Stromal Cells

scholarly journals Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Paola Di Francesco ◽  
Pauline Cajon ◽  
Christophe Desterke ◽  
Marie-France Perron Lepage ◽  
Jean-Jacques Lataillade ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Wound Repair ◽  
Positive Impact ◽  
Early Stage ◽  
Full Thickness ◽  
Skin Punch Biopsy ◽  
Significant Difference

Objective. To assess the clinical value and safety of the application of allogeneic equine oral mucosa mesenchymal stromal cells (OM-MSCs) to wounds. Animals. 8 healthy adult horses without front limb skin lesions or musculoskeletal disease. Procedures. Stem cells were isolated from the oral mucosa of a donor horse. Horses were subjected to the creation of eight full-thickness cutaneous wounds, two on each distal forelimb (FL) and two on both sides of the thorax (TH). Each wound was subjected to one out of four treatments: no medication (T1), hyaluronic acid- (HA-) gel containing OM-MSC (T2), HA-gel containing OM-MSC secretome (T3), and HA-gel alone (T4). Gross macroscopic evaluation and laser digital photographic documentation were regularly performed to allow wound assessment including wound surface area. Full-thickness skin punch biopsy was performed at each site before wound induction (D0, normal skin) and after complete wound healing (D62, repaired skin). Results. All wounds healed without adverse effect at D62. Distal limb wounds are slower to heal than body wounds. OM-MSC and its secretome have a positive impact on TH wound contraction. OM-MSC has a positive impact on the contraction and epithelialization of FL wounds. No significant difference between wound sites before and after treatment was noted at histological examination. Conclusion and Clinical Relevance. Using horse cells harvested from oral mucosa is a feasible technique to produce OM-MSC or its secretome. The gel produced by the combination of these biologic components with HA shows a positive impact when applied during the early stage of wound healing.

Are Stromal Cells of Adipose Tissue From Multiple Myeloma Patients Are Normal ? A Comparison of Adipose Derived Stromals Cells From Healthy Donors and Multiple Myeloma Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3993-3993
Author(s):  
Benjamin Hebraud ◽  
Elodie Labat ◽  
Nicolas Espagnolle ◽  
Melanie Gadelorge ◽  
Louis Casteilla ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adipose Tissue ◽  
Board Of Directors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Proliferation Rate ◽  
Population Doubling ◽  
Advisory Committees ◽  
Osteoblast Function ◽  
Significant Difference

Abstract Abstract 3993 Introduction: One of the main feature of MM is bone disease resulting from an increased osteoclastic activity and inhibition of osteoblast function; this imbalance also promotes MM growth leading to a vicious circle. Interestingly mature osteoblasts reduce osteoclastogenesis via high levels of OPG and reduced levels of RANKL and have anti-MM effect too, especially via decorin causing MM cells apoptosis. Hence, therapeutic approaches restoring osteoblast function could reduce osteoclastogenesis and MM growth. Mature osteoblasts originate from bone marrow mesenchymal stromal cells (MSC) that are key component of MM microenvironment. We and others showed that MSC from patients with MM are abnormal. In particular, they have an impaired capacity to diffentiate into osteoblasts. Hence we studied mesenchymal stromal cells from adipose tissue (AT) called the Adipose derived Stromal Cells (ASC). They have very similar properties than MSC, in particular osteoblastic differentiation capacity. The aim of our work is to demonstrate that ASC from patients with MM are normal, contrary to their MSC; we propose the first study comparing ASC from MM patients and ASC from Healthy Donor (HD) with functional and genomics tests. Patients and Methods: We studied ASC from 15 patients with newly diagnosed MM (MM ASC) and CRAB symptoms and from 15 HD (HD ASC) between 18 and 65 years. The stromal vascular fraction was isolated from subcutaneous AT by centrifugation and enzymatic digestion. The ASC were sorted by adhesion to the plastic flask and expanded for 3 passages of 21 days in culture medium MEMa containing 10% FBS and ciprofloxacine. We perform: Results: Our data confirm the stromal nature of MM and HD ASC. The cells were adherent and proliferate into plastic flasks; able to differentiate into osteogenic, chondrogenic and adipogenic lineage; positive for CD90, CD73, CD105 and negative for CD14, CD45. We next found that MM and HD ASC have the same expansion capacity (HD 470±45, MM 208±194, p=0.13), cell population doubling (HD 16.0±0.3, MM 15.0±1.3 p=0,17), and progenitor frequency (HD 3.4%±3, MM 3.7±5,5%, p=0.166). Phenotype didn't show any significant difference except for CD200. Osteogenic, chondrogenic and adipogenic differentiation assays didn't show any difference according to the origin of ASC; alizarin (mmol/l): HD 2.66±0.6, MM 2.15±2.1 p=0.15, chondroitin sulfate (ng/ml): HD 0.5±0.17, MM 0.58±0.58 p=0.2, glycerol (mg/well): HD 2.7±1.6, MM 3.28±1.2 p=0.26. Measurement of IL-6 (HD 7143±10029, MM 10192±6379 pg/ml p=0.15), DKK1 (HD 16698±2432, MM 15948±6558 pg/ml p=0.98), and GDF15 (HD 0.29±0.3, MM 0.43±0.37 ng/ml p=0.13) shows similar levels in both population. We then analysed proliferation rate of MOLP-6 in co-culture with ASC and observed no difference (proliferation rate HD 1.49±0.34, MM 1.66±0.80 p=0,33). MM ASC and HD ASC had the same capacity to support haematopoiesis. Finally, genomic analysis performed by GEP did not identify any difference between the two groups. miRNA analysis tested 1036 targets and found only one, HSA-MIR-196A, differentially expressed between HD and MM ASC(p=0,014). Conclusion: To our knowledge, this is the first exhaustive study that compare ASC from MM patients and HD. Our results strongly suggest that MM ASC are normal and could potentially be used in autologous stem cell transplantation in order to restore the patients' osteoblastic function. Disclosures: Roussel: celgene: Honoraria; janssen: Honoraria. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees.

Secretomes from bone marrow–derived mesenchymal stromal cells enhance periodontal tissue regeneration

Cytotherapy ◽  
2015 ◽  
Vol 17 (4) ◽  
pp. 369-381 ◽  
Author(s):  
Takamasa Kawai ◽  
Wataru Katagiri ◽  
Masashi Osugi ◽  
Yukiko Sugimura ◽  
Hideharu Hibi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Periodontal Tissue ◽  
Periodontal Tissue Regeneration

scholarly journals Utilizing Autologous Multipotent Mesenchymal Stromal Cells andβ-Tricalcium Phosphate Scaffold in Human Bone Defects: A Prospective, Controlled Feasibility Trial

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Pavel Šponer ◽  
Stanislav Filip ◽  
Tomáš Kučera ◽  
Jindra Brtková ◽  
Karel Urban ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tricalcium Phosphate ◽  
Bone Defects ◽  
Feasibility Trial ◽  
Harris Hip Score ◽  
Controlled Study ◽  
Control Group ◽  
Trial Group ◽  
Significant Difference

The purpose of this prospective controlled study was to compare healing quality following the implantation of ultraporousβ-tricalcium phosphate, containing either expanded autologous mesenchymal stromal cells (trial group, 9 patients) orβ-tricalcium phosphate alone (control group, 9 patients), into femoral defects during revision total hip arthroplasty. Both groups were assessed using the Harris Hip Score, radiography, and DEXA scanning at 6 weeks and 3, 6, and 12 months postoperatively. A significant difference in the bone defect healing was observed between both groups of patients (P<0.05). In the trial group, trabecular remodeling was found in all nine patients and in the control group, in 1 patient only. Whereas, over the 12-month follow-up period, no significant difference was observed between both groups of patients in terms of the resorption ofβ-tricalcium phosphate, the significant differences were documented in the presence of radiolucency and bone trabeculation through the defect (P<0.05). Using autologous mesenchymal stromal cells combined with aβ-tricalcium phosphate scaffold is a feasible, safe, and effective approach for management of bone defects with compromised microenvironment. The clinical trial was registered at the EU Clinical Trials Register before patient recruitment has begun (EudraCT number2012-005599-33).

scholarly journals Overexpression of IL-10 Enhances the Efficacy of Human Umbilical-Cord-Derived Mesenchymal Stromal Cells in E. coli Pneumosepsis

2019 ◽  
Vol 8 (6) ◽  
pp. 847 ◽  
Author(s):  
Mirjana Jerkic ◽  
Claire Masterson ◽  
Lindsay Ormesher ◽  
Stéphane Gagnon ◽  
Sakshi Goyal ◽  
...  
Keyword(s):  
Lung Injury ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Injury Severity ◽  
Therapeutic Potential ◽  
Human Macrophage ◽  
Human Umbilical Cord ◽  
Macrophage Function ◽  
E Coli

Enhancing the immunomodulatory effects of mesenchymal stromal cells (MSCs) may increase their effects in sepsis. We tested the potential for overexpression of Interleukin-10 (IL-10) in human umbilical cord (UC) MSCs to increase MSC efficacy in Escherichia coli (E. coli) pneumosepsis and to enhance human macrophage function. Pneumonia was induced in rats by intratracheal instillation of E. coli ((2.0–3.0) × 109 Colony forming units (CFU)/kg). One hour later, animals were randomized to receive (a) vehicle; (b) naïve UC-MSCs; or (c) IL-10 overexpressing UC-MSCs (1 × 107 cells/kg). Lung injury severity, cellular infiltration, and E. coli colony counts were assessed after 48 h. The effects and mechanisms of action of IL-10 UC-MSCs on macrophage function in septic rodents and in humans were subsequently assessed. Survival increased with IL-10 (9/11 (82%)) and naïve (11/12 (91%)) UC-MSCs compared to vehicle (9/15 (60%, p = 0.03). IL-10 UC-MSCs—but not naïve UC-MSCs—significantly decreased the alveolar arterial gradient (455 ± 93 and 520 ± 81, mmHg, respectively) compared to that of vehicle animals (544 ± 52, p = 0.02). Lung tissue bacterial counts were significantly increased in vehicle- and naïve-UC-MSC-treated animals but were not different from sham animals in those treated with IL-10 overexpressing UC-MSCs. IL-10 (but not naïve) UC-MSCs decreased alveolar neutrophils and increased alveolar macrophage percentages compared to vehicle. IL-10 UC-MSCs decreased structural lung injury compared to naïve UC-MSC or vehicle therapy. Alveolar macrophages from IL-10-UC-MSC-treated rats and from human volunteers demonstrated enhanced phagocytic capacity. This was mediated via increased macrophage hemeoxygenase-1, an effect blocked by prostaglandin E2 and lipoxygenase A4 blockade. IL-10 overexpression in UC-MSCs enhanced their effects in E. coli pneumosepsis and increased macrophage function. IL-10 UC-MSCs similarly enhanced human macrophage function, illustrating their therapeutic potential for infection-induced acute respiratory distress syndrome (ARDS).

scholarly journals Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques

2020 ◽  
Vol 21 (12) ◽  
pp. 4382 ◽  
Author(s):  
Sebastian Walter ◽  
Thomas Randau ◽  
Cäcilia Hilgers ◽  
El-Mustapha Haddouti ◽  
Werner Masson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
Donor Site ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differentiation Potential ◽  
Significant Difference ◽  
Harvesting Techniques

Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field.

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