Effect of Human Wharton's Jelly Mesenchymal Stem Cell Paracrine Signaling on Keloid Fibroblasts

Arno, Anna; Amini-Nik, Saeid; Blit, Patrick H.; Al-Shehab, Mohammed; Belo, Cassandra; Herer, Elaine; Jeschke, Marc G.

doi:10.5966/sctm.2013-0120

Cited by 53 publications

(61 citation statements)

References 55 publications

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“…H&E and ORO staining of WAT as well as IHC staining of perilipin in liver were performed as described previously (15,16). The size of adipocytes was measured using ImageJ v1.48 (NIH).…”

Section: Hematoxylin and Eosin (Hande) Oro Immunohistochemical (Ihc) mentioning

confidence: 99%

Alternative Mechanism for White Adipose Tissue Lipolysis after Thermal Injury

Patsouris

Sadri

et al. 2015

Mol Med

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Extensively burned patients often suffer from sepsis, a complication that enhances postburn hypermetabolism and contributes to increased incidence of multiple organ failure, morbidity and mortality. Despite the clinical importance of burn sepsis, the molecular and cellular mechanisms of such infection-related metabolic derangements and organ dysfunction are still largely unknown. We recently found that upon endoplasmic reticulum (ER) stress, the white adipose tissue (WAT) interacts with the liver via inflammatory and metabolic signals leading to profound hepatic alterations, including hepatocyte apoptosis and hepatic fatty infiltration. We therefore hypothesized that burn plus infection causes an increase in lipolysis of WAT after major burn, partially through induction of ER stress, contributing to hyperlipidemia and profound hepatic lipid infiltration. We used a two-hit rat model of 60% total body surface area scald burn, followed by intraperitoneal (IP) injection of Pseudomonas Aeruginosa-derived lipopolysaccharide (LPS) 3 d postburn. One day later, animals were euthanized and liver and epididymal WAT (EWAT) samples were collected for gene expression, protein analysis and histological study of inflammasome activation, ER stress, apoptosis and lipid metabolism. Our results showed that burn plus LPS profoundly increased lipolysis in WAT associated with significantly increased hepatic lipid infiltration. Burn plus LPS augmented ER stress by upregulating CHOP and activating ATF6, inducing NLRP3 inflammasome activation and leading to increased apoptosis and lipolysis in WAT with a distinct enzymatic mechanism related to inhibition of AMPK signaling. In conclusion, burn sepsis causes profound alterations in WAT and liver that are associated with changes in organ function and structure.

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“…H&E and ORO staining of WAT as well as IHC staining of perilipin in liver were performed as described previously (15,16). The size of adipocytes was measured using ImageJ v1.48 (NIH).…”

Section: Hematoxylin and Eosin (Hande) Oro Immunohistochemical (Ihc) mentioning

confidence: 99%

Alternative Mechanism for White Adipose Tissue Lipolysis after Thermal Injury

Patsouris

Sadri

et al. 2015

Mol Med

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“…There is a substantial amount of literature which investigate the beneficial effects of cellular therapy with WJ-MSCs, alone or within a scaffold (Zebardast et al, 2010; Azari et al, 2011; Shohara et al, 2012; Arno et al, 2014; Fong et al, 2014; Ribeiro et al, 2014; Sabapathy et al, 2014). Emerging reports are showing the promising role of decellularized biological matrices for tissue repair (Boccafoschi et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have elucidated the role of WJ-MSCs for various applications, such as for neurological disorders (Shalitin et al, 2003), kidney injury (Du et al, 2013), lung injury (Moodley et al, 2009), liver injury and cancer therapy (Sabapathy et al, 2014). We have recently reported that WJ-MSCs conditioned-medium with its secretome has positive effects on wound healing in vitro (Arno et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Acellular Gelatinous Material of Human Umbilical Cord Enhances Wound Healing: A Candidate Remedy for Deficient Wound Healing

et al. 2017

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Impaired wound healing is a severe clinical challenge and research into finding effective wound healing strategies is underway as there is no ideal treatment. Gelatinous material from the umbilical cord called Wharton's jelly is a valuable source of mesenchymal stem cells which have been shown to aid wound healing. While the cellular component of Wharton's jelly has been the subject of extensive research during the last few years, little is known about the de-cellularized jelly material of the umbilical cord. This is important as they are native niche of stem cells. We have isolated Wharton's jelly from umbilical cords and then fractionated acellular gelatinous Wharton's jelly (AGWJ). Here, we show for the first time that AGWJ enhances wound healing in vitro as well as in vivo for wounds in a murine model. In vivo staining of the wounds revealed a smaller wound length in the AGWJ treated wounds in comparison to control treatment by enhancing cell migration and differentiation. AGWJ significantly enhanced fibroblast cell migration in vitro. Aside from cell migration, AGWJ changed the cell morphology of fibroblasts to a more elongated phenotype, characteristic of myofibroblasts, confirmed by upregulation of alpha smooth muscle actin using immunoblotting. AGWJ treatment of wounds led to accelerated differentiation of cells into myofibroblasts, shortening the proliferation phase of wound healing. This data provides support for a novel wound healing remedy using AGWJ. AGWJ being native biological, cost effective and abundantly available globally, makes it a highly promising treatment option for wound dressing and skin regeneration.

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“…It is suggested that human mesenchymal stem cells could have antifi brotic properties with paracrine signalling as one of the main underlying mechanisms behind their therapeutic eff ects. Th is therapeutical property might possibly be valuable when treating keloids and renal scarring [3,13]. Similarly experimental studies have shown the ability of the Wharton's jelly-derived mesenchymal stem cells to diff erentiate into adipocytelike cells with high chemokine secreting properties [2].…”

Section: Introductionmentioning

confidence: 99%