Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

Walter, Merlin Nathaniel Mark; Wright, Karina; Fuller, Heidi R.; MacNeil, Sheila; Johnson, William E.

doi:10.1016/j.yexcr.2010.02.026

Cited by 426 publications

(379 citation statements)

References 48 publications

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“…Indeed, BM-MSC conditioned medium can promote and accelerate wound healing in vitro. 35,36 To test whether kidney MSC-like cells can facilitate repair, a scratch wound repair assay was performed. Madin-Darby Canine Kidney (MDCK) cells were cultured to confluence, subjected to scratch injury, and continuously cultured in the presence of normal culture medium or conditioned medium from Bulk or Hoxb7-derived kidney MSC-like cells.…”

Section: Repair Activity Of Kidney-derived Stromal Cells In Scrape Inmentioning

confidence: 99%

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

Ariunbold

Suhaimi

et al. 2015

Journal of the American Society of Nephrology

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We previously described a mesenchymal stem cell (MSC)-like population within the adult mouse kidney that displays long-term colony-forming efficiency, clonogenicity, immunosuppression, and panmesodermal potential. Although phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent protein (GFP) mice identified the collecting duct as a source of kidney MSC-like cells, with these cells undergoing an epithelialto-mesenchymal transition to form clonogenic, long-term, self-renewing MSC-like cells. Notably, after extensive passage, kidney MSC-like cells selectively integrated into the aquaporin 2-positive medullary collecting duct when microinjected into the kidneys of neonatal mice. No epithelial integration was observed after injection of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial structures in vitro and in vivo, and conditioned media from these cells supported epithelial repair in vitro. mice revealed evidence for the intercalation of a Wnt4-expressing interstitial population into the neonatal collecting duct, suggesting that such intercalation may represent a normal developmental mechanism giving rise to a distinct collecting duct subpopulation. These results extend previous observations of papillary stem cell activity and collecting duct plasticity and imply a role for such cells in collecting duct formation and, possibly, repair.

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Section: Repair Activity Of Kidney-derived Stromal Cells In Scrape Inmentioning

confidence: 99%

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

Ariunbold

Suhaimi

et al. 2015

Journal of the American Society of Nephrology

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“…Indeed, a recent study by Walter et al showed that MSC CM significantly enhances wound closure rates, whereas CM from L929 or HaCaT cultures does not, an effect that seems to be a consequence of accelerated cell migration. 21 In addition, MSC-derived CM promotes proliferation of cardiac progenitor cells and inhibits apoptosis induced by hypoxia and serum starvation. 42 More recently, Jung et al showed that ex vivo culture of MSCs in the presence of human cord blood serum results in selective activation of platelet-derived THERAPY WITH HUMAN UCB-MSCS AND CONDITIONED MEDIUM IN OVX NUDE MICEgrowth factor and epidermal growth factor signals in MSCs, and that the cells exhibit higher self-renewal and enhanced osteogenic potential.…”

Section: Discussionmentioning

confidence: 99%

“…Several recent lines of evidence also support the hypothesis that therapeutic effects of stem cell transplantation are derived from secretory factors rather than by direct cell replacement. Indeed, a conditioned medium (CM) from MSCs has been shown to improve cardiac function after myocardial infarction, 18,19 accelerate wound healing, 20,21 and have neuroprotective effects. 22 Although BM has been most commonly utilized as a source of MSCs, the number and multilineage differentiation capacity decline with the age or health condition of donors.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

Park

Song

et al. 2013

Tissue Engineering Part A

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Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCBMSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

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“…20,38 In vitro, the cytokines or mediators secreted by MSCs including TGF-b1, IL-6 and IL-8 accelerate skin wound healing rather than increase cell proliferation. 39 Walker et al demonstrated that direct implantation of MSCs enhances neuroprotection via stimulation of the neuronal stem cell nuclear factor jB activity leading to up-regulation of IL-6 production and rescue cells from apopotosis. 40 Further studies will be required to investigate the therapeutic potential of activated IL-6/gp130-mediated STAT3 signaling pathway in MSCs in hepatocyte regeneration.…”

Section: Discussionmentioning

confidence: 99%

Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration

et al. 2010

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Adult bone marrow-derived mesenchymal stem cells (MSCs) exist in all living species and are capable of differentiating into different types of specific cells. In this study, we demonstrate the therapeutic effectiveness of rat MSC transplantation in D-galactosamine (GalN)-induced acute liver injury and identified the novel pathways which are involved in hepatic differentiation of MSCs. In vivo, intraportal transplantation with 5 Â 10 6 MSCs at 24 hours after GalN administration resulted in significant reduction in serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin compared to the control group. Engrafted MSCs actively proliferated, differentiated, and further enhanced hepatocyte proliferation activity. In vitro, coculture of MSCs with GalN-induced injured hepatocytes showed efficient differentiation and was evidenced by progressive increase in messenger RNA levels of hepatic markers, including albumin, a-fetoprotein, CCAAT-enhancer binding protein a, a-1-antitryspin, and hepatocyte nuclear factor-3b. Immunofluorescent staining revealed that these cells were positive for albumin, a-fetoprotein, and cytokeratin 18, but not clusters of differentiation 34, cytokeratin 19, or OV6. During hepatic differentiation, signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling were constantly activated, and a gradual down-regulation of b-catenin expression in messenger RNA and protein levels was detected. Hyper-interleukin-6 fusion protein but not interleukin-6 (IL-6) alone caused reduction in b-catenin expression associated with the up-regulation of Wnt-5a in MSCs via activating the glycoprotein 130 (gp130)-mediated STAT3 signaling pathway, which indicates the operation of the trans-signaling mechanism. Activation of IL-6/gp130-mediated STAT3 signaling pathway in MSCs triggered wound healing, cell migration, and proliferation. In conclusion, transplantation of MSCs promotes cell proliferation and organ repair, and activation of IL-6/gp130-mediated STAT3 signaling pathway via soluble IL-6 receptor is crucial in hepatic differentiation of MSCs. Liver Transpl 16:1195-1206. V C 2010 AASLD. Received February 19, 2010 accepted July 7, 2010. Additional Supporting Information may be found in the online version of this article.Abbreviations: AFP, a-fetoprotein; ALT, alanine aminotransferase; APC, adenomatous polyposis coli; AR, androgen receptor; AST, aspartate aminotransferase; CEBP, CCAAT/enhancer binding protein; CK, cytokeratin; CTNN b 1, b-catenin; DAPI, 4 0 ,6-diamidino-2-phenylindole; DVL1, dishevelled; ERK, extracellular signal-regulated kinase; FISH, fluorescent in situ hybridization; FITC, fluorescein isothiocyanate; DMEM, Dulbecco's modified Eagle medium; FBS, fetal bovine serum; GalN, D-galactosamine; GFP, green fluorescent protein; GSK3bglycoprotein synthase kinase 3b; IL, interleukin; IP, immunoprecipitation; MAPK, mitogenactivated protein kinase; mRNA, messenger RNA; MSC, mesenchy...

show abstract

Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

Cited by 426 publications

References 48 publications

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity

Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration

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