The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture

Laco, Filip; Ma, Kui; Weber, H. J.; Ramakrishna, Seeram; Chan, Casey K.

doi:10.1016/j.jdermsci.2009.05.009

Cited by 31 publications

(17 citation statements)

References 35 publications

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“…When keratinocytes were overlaid on fibroblasts, a skin-like structure formed in some studies [37]–[39]. A similar result was obtained in our current study.…”

Section: Discussionsupporting

confidence: 91%

Enhanced Keratinocyte Proliferation and Migration in Co-culture with Fibroblasts

Wang

Farhangfar³

et al. 2012

PLoS ONE

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Wound healing is primarily controlled by the proliferation and migration of keratinocytes and fibroblasts as well as the complex interactions between these two cell types. To investigate the interactions between keratinocytes and fibroblasts and the effects of direct cell-to-cell contact on the proliferation and migration of keratinocytes, keratinocytes and fibroblasts were stained with different fluorescence dyes and co-cultured with or without transwells. During the early stage (first 5 days) of the culture, the keratinocytes in contact with fibroblasts proliferated significantly faster than those not in contact with fibroblasts, but in the late stage (11th to 15th day), keratinocyte growth slowed down in all cultures unless EGF was added. In addition, keratinocyte migration was enhanced in co-cultures with fibroblasts in direct contact, but not in the transwells. Furthermore, the effects of the fibroblasts on keratinocyte migration and growth at early culture stage correlated with heparin-binding EGF-like growth factor (HB-EGF), IL-1α and TGF-β1 levels in the cultures where the cells were grown in direct contact. These effects were inhibited by anti-HB-EGF, anti-IL-1α and anti-TGF-β1 antibodies and anti-HB-EGF showed the greatest inhibition. Co-culture of keratinocytes and IL-1α and TGF-β1 siRNA-transfected fibroblasts exhibited a significant reduction in HB-EGF production and keratinocyte proliferation. These results suggest that contact with fibroblasts stimulates the migration and proliferation of keratinocytes during wound healing, and that HB-EGF plays a central role in this process and can be up-regulated by IL-1α and TGF-β1, which also regulate keratinocyte proliferation differently during the early and late stage.

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“…When keratinocytes were overlaid on fibroblasts, a skin-like structure formed in some studies [37]–[39]. A similar result was obtained in our current study.…”

Section: Discussionsupporting

confidence: 91%

Enhanced Keratinocyte Proliferation and Migration in Co-culture with Fibroblasts

Wang

Farhangfar³

et al. 2012

PLoS ONE

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“…In vitro, conditioned media obtained from BM‐MSCs significantly enhanced the cell survival ability of fibroblast cells, promoted the production or secretion of ECM proteins, and suppressed collagenase (MMP1) expression . A dose‐related effect of media from BM‐MSCs on epidermal development was found in organotypic co‐culture …”

mentioning

confidence: 96%

Deep dermal fibroblast profibrotic characteristics are enhanced by bone marrow–derived mesenchymal stem cells

Ding

Shankowsky

et al. 2013

Wound Repair Regeneration

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Hypertrophic scars are a significant fibroproliferative disorder complicating deep injuries to the skin. We hypothesize that activated deep dermal fibroblasts are subject to regulation by bone marrow-derived mesenchymal stem cells (BM-MSCs), which leads to the development of excessive fibrosis following deep dermal injury. We found that the expression of fibrotic factors was higher in deep burn wounds compared with superficial burn wounds collected from burn patients with varying depth of skin injury. We characterized deep and superficial dermal fibroblasts, which were cultured from the deep and superficial dermal layers of normal uninjured skin obtained from abdominoplasty patients, and examined the paracrine effects of BM-MSCs on the fibrotic activities of the cells. In vitro, deep dermal fibroblasts were found higher in the messenger RNA (mRNA) levels of type 1 collagen, alpha smooth muscle actin, transforming growth factor beta, stromal cell-derived factor 1, and tissue inhibitor of metalloproteinase 1, an inhibitor of collagenase (matrix metalloproteinase 1). As well, deep dermal fibroblasts had low matrix metalloproteinase 1 mRNA, produced more collagen, and contracted collagen lattices significantly greater than superficial fibroblasts. By co-culturing layered fibroblasts with BM-MSCs in a transwell insert system, BM-MSCs enhanced the fibrotic behavior of deep dermal fibroblasts, which suggests a possible involvement of BM-MSCs in the pathogenesis of hypertrophic scarring.

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“…In accordance, using systemic delivery, only 720 of each million injected cells were retrieved 3 days later . Even in the context of skin organotypic cultures, one study reported that 10% MSCs combined with 90% fibroblasts produced the best support for keratinocyte growth and differentiation and excess MSCs was actually deleterious . The most compelling reports of engraftment come from models of radiation induced burns where engraftment and long‐term persistence of autologous MSCs could be observed in mice and non‐human primates .…”

Section: The Reasons Behind Mscs' Successmentioning

confidence: 99%

Mesenchymal stem cell therapy in skin: why and what for?

Khosrotehrani

2013

Experimental Dermatology

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In recent years, few stem cells have gained as much clinical notoriety as mesenchymal stem cells. Indeed, MSCs are already in use for a range of systemic inflammatory and autoimmune conditions that also affect the skin, such as acute and chronic graft versus host disease or lupus erythematosus. Most interestingly, these cells are able to improve skin wound healing in multiple preclinical models and few patient series. An additional potential of these cells is the delivery of missing structural elements in skin inherited disorders. However, we here contend that MSCs are not appropriate for cell replacement therapies in the context of wound healing. Indeed, engraftment of cells in the dermis is poor in the absence of irradiation and the observed effects seem mainly due to paracrine factors. In this viewpoint, we favour the hypothesis of a replete niche and competition with resident mesenchymal populations in the dermis not allowing the engraftment of newly delivered MSCs. Consequently, we propose that the benefit of MSCs may be at least in part reproduced by the growth factors or immunomodulatory molecules that they produce. In any case, the rapid progress in this field has allowed the emergence of important questions in skin biology that need to be addressed in parallel with the predictable future use of MSCs in the clinic.

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The dose effect of human bone marrow-derived mesenchymal stem cells on epidermal development in organotypic co-culture

Cited by 31 publications

References 35 publications

Enhanced Keratinocyte Proliferation and Migration in Co-culture with Fibroblasts

Enhanced Keratinocyte Proliferation and Migration in Co-culture with Fibroblasts

Deep dermal fibroblast profibrotic characteristics are enhanced by bone marrow–derived mesenchymal stem cells

Mesenchymal stem cell therapy in skin: why and what for?

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