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

Abstract 182: Increased Adipose-Derived Mesenchymal Stem Cells Counts and Pro-B-Type Natriuretic Peptide in Patients With Critical Limb Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Houssam Farres ◽  
Caroline Sutton ◽  
Abba Zubair ◽  
John D Dortch ◽  
Albert Hakaim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Natriuretic Peptide ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Human Model ◽  
Differentiation Potential ◽  
Paracrine Effects ◽  
Ischemic Group ◽  
Vascular Regeneration

Mesenchymal stem cells (MSCs) have been shown to improve regeneration of injured tissues in vivo. Several in vitro studies and animal models have demonstrated improvement in MSCs paracrine effects under hypoxic conditions. Moreover, several studies suggested that the pro B-type natriuretic peptide (pro-BNP) could be involved in the stimulation of postischemic vascular regeneration. The purpose of this study was to investigate the effect of critical limb ischemia, in a human model, on in-situ adipose derived mesenchymal stem cells (ADMSCs) and to determine whether serum levels of N-terminal pro-BNP correlate with ADMSCs counts and associated paracrine effects. Lipoaspirate samples of ≥ 10mL were collected from ischemic limbs (ischemic group) and compared to control (without ischemia). MSCs were characterized by frequency, viability, differentiation potential, cytokines expression, and cell surface markers. Serum NT pro-BNP was measured as well. MSCs counts were 9-to-10-fold higher in patients with ischemic limbs (mean 7952 MSC/mL ± 542) than controls (mean 790 MSC/mL ± 65). Pro-BNP levels (1878-4757 pg/mL) were approximately 8-to-26-fold higher than in age- and sex-matched controls. Furthermore, there were positive correlations between pro-BNP levels and MSCs counts in the ischemic group. In conclusion, patients with critical limb ischemia (CLI) have higher levels of pro-BNP and MSCs counts than controls. Increased levels of pro-BNP and MSCs counts can be considered humoral and cellular surrogates of ischemia and hypoxia in patients with CLI. This supports recent studies that suggest that the increase production of peripheral BNP may be a stem cells-mediated response to stimulate angiogenesis in the ischemic skeletal muscles.

scholarly journals Mesenchymal stem cells and vascular regeneration

2017 ◽  
Vol 24 (1) ◽  
pp. e12324 ◽  
Author(s):  
Wenduo Gu ◽  
Xuechong Hong ◽  
Claire Potter ◽  
Aijuan Qu ◽  
Qingbo Xu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
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.

scholarly journals Pentraxin-3 and galectin-1 are key mediators of the cardioprotective paracrine effects exerted by fetal mesenchymal stem cells isolated from human placenta

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P3271-P3271
Author(s):  
P. Danieli ◽  
F. Copes ◽  
L. Dekker ◽  
G. Malpasso ◽  
M. Roccio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Placenta ◽  
Pentraxin 3 ◽  
Paracrine Effects

scholarly journals Therapeutic Potential of HUMSCs in Female Reproductive Aging

2021 ◽  
Vol 9 ◽  
Author(s):  
Qiaojuan Mei ◽  
Hongbei Mou ◽  
Xuemei Liu ◽  
Wenpei Xiang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Ovarian Function ◽  
Therapeutic Potential ◽  
Human Umbilical Cord ◽  
Great Success ◽  
Reproductive Aging ◽  
Paracrine Factors ◽  
Paracrine Effects

With the development of regenerative medicine, stem cells are being considered more frequently for the treatment of reproductive aging. Human umbilical cord mesenchymal stem cells have been reported to improve the reserve function of aging ovaries through their homing and paracrine effects. In this process, paracrine factors secreted by stem cells play an important role in ovarian recovery. Although the transplantation of human umbilical cord mesenchymal stem cells to improve ovarian function has been studied with great success in animal models of reproductive aging, their application in clinical research and therapy is still relatively rare. Therefore, this paper reviews the role of human umbilical cord mesenchymal stem cells in the treatment of reproductive aging and their related mechanisms, and it does so in order to provide a theoretical basis for further research and clinical treatment.

scholarly journals Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9262
Author(s):  
Huey-Shan Hung ◽  
Kai-Bo Chang ◽  
Cheng-Ming Tang ◽  
Tian-Ren Ku ◽  
Mei-Lang Kung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Silver Nanoparticles ◽  
Mesenchymal Stem Cells ◽  
Superior Performance ◽  
In Vivo Studies ◽  
Vascular Regeneration ◽  
Anti Inflammatory

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

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