scholarly journals Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes

Aging ◽  
2016 ◽  
Vol 8 (8) ◽  
pp. 1703-1717 ◽  
Author(s):  
Julia Platas ◽  
Maria Isabel Guillén ◽  
Maria Dolores Pérez del Caz ◽  
Francisco Gomar ◽  
Miguel Angel Castejón ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Paracrine Effects ◽  
Inflammatory Stress ◽  
Osteoarthritic Chondrocytes

scholarly journals Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Miguel Tofiño-Vian ◽  
Maria Isabel Guillén ◽  
María Dolores Pérez del Caz ◽  
Miguel Angel Castejón ◽  
Maria José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Relevant Factor ◽  
Paracrine Effects ◽  
Inflammatory Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL-) 1βindicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associatedβ-galactosidase activity and the accumulation ofγH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin

2012 ◽  
Vol 83 (3) ◽  
pp. 267-275 ◽  
Author(s):  
Stefan Schlosser ◽  
Cyrill Dennler ◽  
Riccardo Schweizer ◽  
Daniel Eberli ◽  
Jens V. Stein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Paracrine Effects ◽  
Vascular Regeneration

A Bone Marrow Population Containing Both Hematopoietic and Mesenchymal Stem Cells Constitutively Expressing Genes Pairs For: SDF1-CXCR4, CX3CL-CXCR1 and for VEGF Improves Vascularization When Implanted to Ischemic Legs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4178-4178
Author(s):  
A. Lange ◽  
W. Witkiewicz ◽  
D. Dlubek ◽  
L. Maslowski ◽  
D. Drabczak-Skrzypek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ankle Brachial Index ◽  
State Committee ◽  
Cell Populations ◽  
Hematopoietic Tissue ◽  
Local Immunity ◽  
Paracrine Effects ◽  
Pain At Rest ◽  
Positive Effect

Abstract The BM contains progenitor cells that give rise to hematopoietic tissue and also more primitive mesenchymal stem cells (MSC) which may differentiate into other tissues including endothelial cells. This potential of BM cells has already been employed in clinical studies suggesting that implantation of autologous BM cells may induce angiogenesis in ischemic tissues. In the present study 10 male pts with critical leg ischemia (41–64 yrs) suffering from pain at rest and/or foot ischemic ulceration (9/10 pts) with ABI (ankle/brachial index) <0.5 in 8/10 pts in whom surgical treatments were exhausted were enrolled in this study. 0.5L of BM obtained from the iliac posterior crest were processed in a Cobe Spectra 6.0 separator to remove RBC and to reduce the number of granulocytes. Fresh BM populations and those after processing were evaluated for phenotype characteristics and for the presence of transcripts for VEGF and for SDF1-CXCR4, CX3CL-CXCR1 gene pair expression. Usually 40 ml of cell suspensions were injected in 0.5 ml portions to ischemic muscles and the fate of the pts was evaluated in an out-pts observation setting for 5–7 mths. The number of WBC implanted was (mean±SEM) 30.2x108±4.5 which contained the following percentages of subpopulations CD34+ 1.58±0.25, CD45−CD34− 10.8±0.96, CD45−CD34−CD90+ 0.1±0.02, CD45−CD34−CD105+ 2.8±0.4, CD45−CD34−CD73+ 0.07±0.01 and 24 CFU-F/106 WBC. The positive effect of implantation was seen 2 days after the procedure with substantial pain reduction from 6.17±0.35 to 4.63±1.03 (p=0.04) 10 days and to 3.66±1.35 3 mths after implantation (p=0.034). ABI improved from 0.47±0.07 before to 0.66±0.06 (p=0.02) 10 days and to 0.66±0.07 (p=0.02) 3 mths after. This improvement was followed by ulceration healing in 5/9 pts (area of ulceration prior to implantation was 502.3±269.2 mm2 and 2 mths after was 32.3±23.6 mm2) in 2 pts ulceration healed completely. In 10 cases arteriography performed 3 mths after implantation documented new arteriole formation in 6 pts. The positive effect may not be long lasting in all pts as in 3/10 pts the pain at rest recurred and in 2 pts ulceration progressed 2 mths after implantation. The positive effect of the treatment could not be attributed to any of the described cell populations separately as evaluated by correlation analysis. In this study we identified cells with MSC characteristics in the BM population that were further enriched in MNC and implanted to ischemic muscles. In fresh BM cell populations and those after cell processing, the transcripts for VEGF and SDF1-CXCR4 and CXCL3-CXCR1 pairs were found. Implantation of these cells resulted in early, intermediate and late effects with pain relief, ischemic ulceration healing and finally arteriole length density, respectively. The pace of improvement suggested that the processed BM population while injected to ischemic muscles may act via cyto-/chemokine release with an analgetic effect and local immunity improvement. Furthermore, ulceration healing seen 10 days after implantation followed by neovascularization is likely due to auto/paracrine effects within a population of MSC that express genes facilitating the homing of vascular progenitors and play a role in new vessels formation. Supp by the grant PBZ-KBN-083/P05/2002 from the Polish State Committee Sci. Res.

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