Role and Function of Mesenchymal Stem Cells on Fibroblast in Cutaneous Wound Healing

Tanaka, Kotaro; Ogino, Ryohei; Yamakawa, Sho; Suda, Shota; Hayashida, Kenji

doi:10.3390/biomedicines10061391

Cited by 14 publications

(6 citation statements)

References 134 publications

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“…Very similar results were published by Pommato et al, where EVs of AT-MSCs and BM-MSCs were used to study beneficial effects on the proliferation capacity and migration of fibroblasts, keratinocytes, and endothelial cells [14]. The mechanism of this activity could be explained by the release of growth factors such as EGF, bFGF, and TGF that increase the proliferation and migration of fibroblasts [35,36]. Very similar results were published by Liu et al from their study focused on the migration and activation of human skin fibroblasts affected by MSC conditioned medium [37].…”

Section: Discussionsupporting

confidence: 63%

Impact of Canine Amniotic Mesenchymal Stem Cell Conditioned Media on the Wound Healing Process: In Vitro and In Vivo Study

Humenik,

Maloveská,

Hudáková

et al. 2023

IJMS

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The aim of this study was to provide a beneficial treatment effect of mesenchymal stem cell products derived from the canine amniotic membrane (AM-MSC) on the complicated wound healing process in dogs. AM-MSCs were characterized in terms of morphology, phenotypic profile, and multilineage differentiation potential. The in vitro study of the effect of canine amniotic mesenchymal stem cell conditioned media (AMMSC-CM) on a primary skin fibroblast cell culture scratch assay showed a decrease in the measured scratch area of about 66.39% against the negative control (Dulbecco’s Modified Eagle’s Medium—32.55%) and the positive control (Dulbecco’s Modified Eagle’s Medium supplemented with FGF2, N2, B27, and EGF—82.077%) after 72 h treatment. In the experimental study, seven dogs with complicated nonhealing wounds were treated with a combination of antibiotics, NSAIDs, and local AMMSC-CM application. After 15 days of therapy, we observed a 98.47% reduction in the wound surface area as opposed to 57.135% in the control group treated by conventional therapy based on debridement of necrotic tissue, antibiotic therapy, pain management, and change of wound dressing.

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Section: Discussionsupporting

confidence: 63%

Impact of Canine Amniotic Mesenchymal Stem Cell Conditioned Media on the Wound Healing Process: In Vitro and In Vivo Study

Humenik,

Maloveská,

Hudáková

et al. 2023

IJMS

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“…In (dermal) wound healing processes, for example, recruited (and activated) MSCs ‘animate’ fibroblasts to produce the appropriate amounts of collagen fibers needed for tissue repair. MSC-secreted factors at the same time prevent scar formation and limit inflammation, fostering a return to a normal healthy state ( 92 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

Budeus,

Unger,

Hess

et al. 2023

Front. Immunol.

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IntroductionMesenchymal stem cells (MSCs) are considered to be the most promising stem cell type for cell-based therapies in regenerative medicine. Based on their potential to home to diseased body sites following a therapeutically application, these cells could (i) differentiate then into organ-specific cell types to locally restore injured cells or, most prominently, (ii) foster tissue regeneration including immune modulations more indirectly by secretion of protective growth factors and cytokines. As tissue-resident stem cells of mesenchymal origin, these cells are morphologically and even molecularly- at least concerning the classical marker genes- indistinguishable from similar lineage cells, particularly fibroblasts.MethodsHere we used microarray-based gene expression and global DNA methylation analyses as well as accompanying computational tools in order to specify differences between MSCs and fibroblasts, to further unravel potential identity genes and to highlight MSC signaling pathways with regard to their trophic and immunosuppressive action.ResultsWe identified 1352 differentially expressed genes, of which in the MSCs there is a strong signature for e.g., KRAS signaling, known to play essential role in stemness maintenance, regulation of coagulation and complement being decisive for resolving inflammatory processes, as well as of wound healing particularly important for their regenerative capacity. Genes upregulated in fibroblasts addressed predominately transcription and biosynthetic processes and mapped morphological features of the tissue. Concerning the cellular identity, we specified the already known HOX code for MSCs, established a potential HOX code for fibroblasts, and linked certain HOX genes to functional cell-type-specific properties. Accompanied methylation profiles revealed numerous regions, especially in HOX genes, being differentially methylated, which might provide additional biomarker potential.DiscussionConclusively, transcriptomic together with epigenetic signatures can be successfully be used for the definition (cellular identity) of MSCs versus fibroblasts as well as for the determination of the superior functional properties of MSCs, such as their immunomodulatory potential.

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“…It is probable that proliferating and actively synthesizing cells of the transplant significantly reduce the concentration of reactive oxygen species through the synthesis of antioxidant defense enzymes (Jena et al, 2023;Chettouh-Hammas et al, 2023). In a series of studies, it has been demonstrated that culturing keratinocytes under unfavorable conditions without the support of fibroblasts or mesenchymal cells leads to the complete death of keratinocytes through apoptosis after 14 days of cultivation (Tanaka et al, 2022, Xu et al, 2023. However, when keratinocytes are cultured on a collagen gel with fibroblasts, they do not undergo apoptosis and actively proliferate (Tahri et al, 2023;Zhang et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

Kot,

Kurbanov

2023

Regul. Mech. Biosyst.

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In the course of radiation therapy, normal cells surrounding the tumor are also irradiated. During and after irradiation, they undergo a series of structural and metabolic changes, which can lead to cell death or transformation. Therefore, when planning and conducting radiation therapy, the effects of radiation on normal cells are taken into account with the aim of predicting and further correcting post-radiation complications, including the development of radiation burns and ulcers. Radiation skin burns are characterized by a prolonged course of the wound healing process, which is accompanied by a sharp decrease in the number of viable cells in the affected tissue from the first hours of irradiation. The type of cell death can significantly impact the effectiveness of radiation therapy and post-radiation complication correction. Therefore, it is important to study the type of their death in irradiated three-dimensional culture on a model of irradiated dermal equivalent, which is widely used today for modeling biological processes. To detect the pathways of cell death, the levels of reactive oxygen species, cell viability, number of cells undergoing autophagy, apoptosis, and necrosis, the content of active caspases 3, 8, and 9 was fluorometrically measured in the irradiated 3D cell culture by laser scanning confocal microscopy. It was determined that the transplantation of fibroblasts and keratinocytes into the irradiated dermal equivalent contributed to an increase in the overall viability of cells of the equivalent and led to a significant decrease in the concentration of free oxygen forms in the irradiated equivalent. Cells within the irradiated equivalent were not evenly distributed in terms of their quantity and viability, with an overall decrease in the cell count over time. A cluster of equivalent cells with significantly higher viability was formed around the transplant. At the same time, the fibroblasts of the transplant were found to be more resistant to the cytotoxic factors of the post-irradiation culture environment compared to keratinocytes. It was demonstrated that non-irradiated dermal equivalent cells predominantly undergo cell death through autophagy, irradiated equivalent cells primarily undergo necrosis, and after the introduction of the transplant, cell death predominantly occurs through apoptosis. In irradiated culture, both with and without transplantation, there is an increase in the content of effector caspase 3. Cells in irradiated culture undergo apoptosis through the mitochondrial mechanism (with a predominance of active caspase 9), while in irradiated culture with the introduction of the transplant, the receptor-mediated mechanism of apoptosis dominates (with a predominance of active caspase 8). The obtained results can be important for the development of new effective methods of therapy for radiation burns, chronic ulcers and wounds of various etiologies.

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Role and Function of Mesenchymal Stem Cells on Fibroblast in Cutaneous Wound Healing

Cited by 14 publications

References 134 publications

Impact of Canine Amniotic Mesenchymal Stem Cell Conditioned Media on the Wound Healing Process: In Vitro and In Vivo Study

Impact of Canine Amniotic Mesenchymal Stem Cell Conditioned Media on the Wound Healing Process: In Vitro and In Vivo Study

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

The determination of fibroblast and keratinocyte death types after their transplantation into γ-irradiated porous scaffold in vitro

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