scholarly journals Biological activity of human mesenchymal stromal cells on polymeric electrospun scaffolds

2019 ◽  
Vol 7 (3) ◽  
pp. 1088-1100 ◽  
Author(s):  
Febriyani F. R. Damanik ◽  
Gabriele Spadolini ◽  
Joris Rotmans ◽  
Silvia Farè ◽  
Lorenzo Moroni
Keyword(s):  
Biological Activity ◽  
Cell Fate ◽  
Structural Properties ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Electrospun Scaffolds ◽  
Human Mesenchymal Stromal Cells ◽  
And Migration

Controlling chemical and structural properties of electrospun scaffolds provide cues to regulate cell fate and migration.

scholarly journals Kindlin-2 Modulates the Survival, Differentiation, and Migration of Induced Pluripotent Cell-Derived Mesenchymal Stromal Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Mohsen Moslem ◽  
Reto Eggenschwiler ◽  
Christian Wichmann ◽  
Raymund Buhmann ◽  
Tobias Cantz ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Interleukin 2 ◽  
Pluripotent Cell ◽  
Scratch Assay ◽  
Cell Fate Decisions ◽  
Migration Potential ◽  
And Migration ◽  
Induced Pluripotent

Kindlin-2 is a multidomain intracellular protein that can be recruited to β-integrin domains to activate signaling, initiate transcriptional programs, and bind to E-cadherin. To explore its involvement in cell fate decisions in mesenchymal cells, we studied the effects of Kindlin-2 modification (overexpression/knockdown) in induced pluripotent cell-derived mesenchymal stromal cells (iPSC-MSCs). Kindlin-2 overexpression resulted in increased proliferation and reduced apoptosis of iPSC-MSCs, as well as inhibition of their differentiation towards osteocytes, adipocytes, and chondrocytes. In contrast, siRNA-mediated Kindlin-2 knockdown induced increased apoptosis and increased differentiation response in iPSC-MSCs. The ability of iPSC-MSCs to adhere to VCAM-1/SDF-1α under shear stress and to migrate in a wound scratch assay was significantly increased after Kindlin-2 overexpression. In contrast, inhibition of mixed lymphocyte reaction (MLR) was generally independent of Kindlin-2 modulation in iPSC-MSCs, except for decreased production of interleukin-2 (IL-2) after Kindlin-2 overexpression in iPS-MSCs. Thus, Kindlin-2 upregulates survival, proliferation, stemness, and migration potential in iPSC-MSCs and may therefore be beneficial in optimizing performance of iPSC-MSC in therapies.

scholarly journals Cefazolin Irreversibly Inhibits Proliferation and Migration of Human Mesenchymal Stromal Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Hakan Pilge ◽  
Julia Fröbel ◽  
Sabine Lensing-Höhn ◽  
Christoph Zilkens ◽  
Rüdiger Krauspe
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Bone Healing ◽  
Stromal Cells ◽  
Human Mesenchymal Stromal Cells ◽  
Antibiotic Drugs ◽  
Term Administration ◽  
And Migration ◽  
Migration Capacity ◽  
Delayed Bone Healing ◽  
Proliferation And Migration

Drugs may have a significant effect on postoperative bone healing by reducing the function of human mesenchymal stromal cells (hMSC) or mature osteoblasts. Although cefazolin is one of the most commonly used antibiotic drugs in arthroplasty to prevent infection worldwide, there is a lack of information regarding how cefazolin affects hMSC and therefore may have an effect on early bone healing. We studied the proliferation and migration capacity of primary hMSC during cefazolin treatment at various doses for up to 3 days, as well as the reversibility of the effects during the subsequent 3 days of culture without the drug. We found a time- and dose-dependent reduction of the proliferation rate and the migratory potential. Tests of whether these effects were reversible revealed that doses ≥250 μg/mL or treatments longer than 24 h irreversibly affected the cells. We are the first to show that application of cefazolin irreversibly inhibits the potential of hMSC for migration to the trauma site and local proliferation. Cefazolin should be administered only at the required dosage and time to prevent periprosthetic infection. If long-term administration is required and delayed bone healing is present, cefazolin application must be considered as a cause of delayed bone healing.

scholarly journals Multi-pronged approach to human mesenchymal stromal cells senescence quantification with a focus on label-free methods

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weichao Zhai ◽  
Jerome Tan ◽  
Tobias Russell ◽  
Sixun Chen ◽  
Dennis McGonagle ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Preclinical Model ◽  
Label Free ◽  
Current Standard ◽  
Differentiation Potential ◽  
Human Mesenchymal Stromal Cells ◽  
Endogenous Fluorophores

AbstractHuman mesenchymal stromal cells (hMSCs) have demonstrated, in various preclinical settings, consistent ability in promoting tissue healing and improving outcomes in animal disease models. However, translation from the preclinical model into clinical practice has proven to be considerably more difficult. One key challenge being the inability to perform in situ assessment of the hMSCs in continuous culture, where the accumulation of the senescent cells impairs the culture’s viability, differentiation potential and ultimately leads to reduced therapeutic efficacies. Histochemical $$\upbeta $$ β -galactosidase staining is the current standard for measuring hMSC senescence, but this method is destructive and not label-free. In this study, we have investigated alternatives in quantification of hMSCs senescence, which included flow cytometry methods that are based on a combination of cell size measurements and fluorescence detection of SA-$$\upbeta $$ β -galactosidase activity using the fluorogenic substrate, C$${_{12}}$$ 12 FDG; and autofluorescence methods that measure fluorescence output from endogenous fluorophores including lipopigments. For identification of senescent cells in the hMSC batches produced, the non-destructive and label-free methods could be a better way forward as they involve minimum manipulations of the cells of interest, increasing the final output of the therapeutic-grade hMSC cultures. In this work, we have grown hMSC cultures over a period of 7 months and compared early and senescent hMSC passages using the advanced flow cytometry and autofluorescence methods, which were benchmarked with the current standard in $$\upbeta $$ β -galactosidase staining. Both the advanced methods demonstrated statistically significant values, (r = 0.76, p $$\le $$ ≤ 0.001 for the fluorogenic C$${_{12}}$$ 12 FDG method, and r = 0.72, p $$\le $$ ≤ 0.05 for the forward scatter method), and good fold difference ranges (1.120–4.436 for total autofluorescence mean and 1.082–6.362 for lipopigment autofluorescence mean) between early and senescent passage hMSCs. Our autofluroescence imaging and spectra decomposition platform offers additional benefit in label-free characterisation of senescent hMSC cells and could be further developed for adoption for future in situ cellular senescence evaluation by the cell manufacturers.

scholarly journals Alloreactive Immune Response Associated to Human Mesenchymal Stromal Cells Treatment: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2991
Author(s):  
Raquel Sanabria-de la Torre ◽  
María I. Quiñones-Vico ◽  
Ana Fernández-González ◽  
Manuel Sánchez-Díaz ◽  
Trinidad Montero-Vílchez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Rejection ◽  
Human Mesenchymal Stromal Cells ◽  
Immunological Profile ◽  
Tolerability Data ◽  
Donor Specific Antibodies ◽  
The Impact ◽  
Hla Mismatches

The well-known immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) are the reason why they are being used for the treatment of many diseases. Because they are considered hypoimmunogenic, MSCs treatments are performed without considering histocompatibility barriers and without anticipating possible immune rejections. However, recent preclinical studies describe the generation of alloantibodies and the immune rejection of MSCs. This has led to an increasing number of clinical trials evaluating the immunological profile of patients after treatment with MSCs. The objective of this systematic review was to evaluate the generation of donor specific antibodies (DSA) after allogeneic MSC (allo-MSC) therapy and the impact on safety or tolerability. Data from 555 patients were included in the systematic review, 356 were treated with allo-MSC and the rest were treated with placebo or control drugs. A mean of 11.51% of allo-MSC-treated patients developed DSA. Specifically, 14.95% of these patients developed DSA and 6.33% of them developed cPRA. Neither the production of DSA after treatment nor the presence of DSA at baseline (presensitization) were correlated with safety and/or tolerability of the treatment. The number of doses administrated and human leucocyte antigen (HLA) mismatches between donor and recipient did not affect the production of DSA. The safety of allo-MSC therapy has been proved in all the studies and the generation of alloantibodies might not have clinical relevance. However, there are very few studies in the area. More studies with adequate designs are needed to confirm these results.

Sign in / Sign up

Export Citation Format

Share Document