Mesenchymal stromal cells reverse hypoxia-mediated suppression of α-smooth muscle actin expression in human dermal fibroblasts

Faulknor, Renea; Olekson, Melissa A.; Nativ, Nir I.; Ghodbane, Mehdi; Gray, Andrea; Berthiaume, François

doi:10.1016/j.bbrc.2015.01.013

Cited by 20 publications

(18 citation statements)

References 29 publications

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“…Taken together, these data suggest that hypoxia significantly impairs IL-10 expression in macrophages, and this impairment is not ameliorated by MSCs. There is an abundance of pre-clinical data showing that MSCs have the ability to modulate inflammation and therefore may improve wound healing 2, 5, 6, 9, 10, 12 . However, this phenomenon was not always proven in human clinical trials 33–35 .…”

Section: Discussionmentioning

confidence: 99%

“…Human bone marrow-derived MSCs were purchased from the Institute of Regenerative Medicine at Texas A&M at passage 1 and cultured as previously described 11, 12 . Briefly, MSCs were cultured in Roswell Park Memorial Institute (RPMI; Life Technologies, Grand Island, NY) 1640 medium, supplemented with 10% fetal bovine serum (FBS; Atlanta Biologicals, Flowery Branch, GA), 1% v/v penicillin-streptomycin (pen-strep; Life Technologies) and 4mM L-glutamine (Life Technologies).…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, MSCs were cultured in Roswell Park Memorial Institute (RPMI; Life Technologies, Grand Island, NY) 1640 medium, supplemented with 10% fetal bovine serum (FBS; Atlanta Biologicals, Flowery Branch, GA), 1% v/v penicillin-streptomycin (pen-strep; Life Technologies) and 4mM L-glutamine (Life Technologies). Passage 3 cells were cultured until 70% confluency and immobilized in alginate sheets as previously described 12 . Briefly, 5 × 10 5 MSCs were mixed with 3% soluble alginate, placed in a 2 × 2cm PDMS mold, and submerged in a 500mM CaCl 2 bath.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were washed briefly with medium and imaged on an Olympus fluorescent microscope using 10× objective. Slidebook software (Intelligent Imaging Innovations, Denver, CO) was used to quantify the number of live (green fluorescence), dead (red fluorescence), and total (blue fluorescence) cells to calculate the percent viability as described elsewhere 12, 15 .…”

Section: Methodsmentioning

confidence: 99%

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Hypoxia impairs mesenchymal stromal cell-induced macrophage M1 to M2 transition

et al. 2017

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The transition of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype is crucial for the progression of normal wound healing. Persistent M1 macrophages within the injury site may lead to an uncontrolled macrophage-mediated inflammatory response and ultimately a failure of the wound healing cascade, leading to chronic wounds. Mesenchymal stromal cells (MSCs) have been widely reported to promote M1 to M2 macrophage transition; however, it is unclear whether MSCs can drive this transition in the hypoxic environment typically observed in chronic wounds. Here we report on the effect of hypoxia (1% O2) on MSCs’ ability to transition macrophages from the M1 to the M2 phenotype. While hypoxia had no effect on MSC secretion, it inhibited MSC-induced M1 to M2 macrophage transition, and suppressed macrophage expression and production of the anti-inflammatory mediator interleukin-10 (IL-10). These results suggest that hypoxic environments may impede the therapeutic effects of MSCs.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Hypoxia impairs mesenchymal stromal cell-induced macrophage M1 to M2 transition

et al. 2017

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“…55 Additionally, MSCs may promote wound healing in response to hypoxia, increasing paracrine secretion of transforming growth factor-β 1 , which in turn can restore fibroblast wound healing functionality inhibited under hypoxic conditions. 56 Despite tolerance, and even activation of stem cells in hypoxic environments, byproducts of tissue hypoxia may be detrimental to their regenerative capabilities. As an example, elevated lactate levels, as are found in chronic wounds, are associated with gene expression in MSCs associated with inflammation and apoptosis.…”

Section: Hypoxiamentioning

confidence: 99%

Stem cells and chronic wound healing: state of the art

Leavitt¹,

Hu²,

Barnes³

et al. 2016

CWCMR

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Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based therapeutics. Stem cells promise improved therapies for healing chronic wounds, but further studies that are well-designed with standardized protocols are necessary for fruition.

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In vivo response to decellularized mesothelium scaffolds

et al. 2017

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Biological surgical scaffolds are used in plastic and reconstructive surgery to support structural reinforcement and regeneration of soft tissue defects. Macrophage and fibroblast cell populations heavily regulate scaffold integration into host tissue following implantation. In the present study, the biological host response to a commercially available surgical scaffold (Meso BioMatrix Surgical Mesh (MBM)) was investigated for up to 9 weeks after subcutaneous implantation; this scaffold promoted superior cell migration and infiltration previously in in vitro studies relative to other commercially available scaffolds. Infiltrating macrophages and fibroblasts phenotypes were assessed for evidence of inflammation and remodeling. At week 1, macrophages were the dominant cell population, but fibroblasts were most abundant at subsequent time points. At week 4, the scaffold supported inflammation modulation as indicated by M1 to M2 macrophage polarization; the foreign body giant cell response resolved by week 9. Unexpectedly, a fibroblast subpopulation expressed macrophage phenotypic markers, following a similar trend in transitioning from a proinflammatory to anti-inflammatory phenotype. Also, α-smooth muscle actin-expressing myofibroblasts were abundant at weeks 4 and 9, mirroring collagen expression and remodeling activity. MBM supported physiologic responses observed during normal wound healing, including cellular infiltration, host tissue ingrowth, remodeling of matrix proteins, and immune modulation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 716-725, 2018.

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Mesenchymal stromal cells reverse hypoxia-mediated suppression of α-smooth muscle actin expression in human dermal fibroblasts

Cited by 20 publications

References 29 publications

Hypoxia impairs mesenchymal stromal cell-induced macrophage M1 to M2 transition

Hypoxia impairs mesenchymal stromal cell-induced macrophage M1 to M2 transition

Stem cells and chronic wound healing: state of the art

In vivo response to decellularized mesothelium scaffolds

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