Human mesenchymal stem cells may be involved in keloid pathogenesis

Akino, Kozo; Akita, Sadanori; Yakabe, Aya; Mineda, Takao; Hayashi, Tomayoshi; Hirano, Akiyoshi

doi:10.1111/j.1365-4632.2008.03380.x

Cited by 28 publications

(35 citation statements)

References 13 publications

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“…They are composed of cells of fibroblast lineage, and exhibit a marked fibrotic response with significant vascularity. Importantly, their histological characteristics are indistinguishable from that of non-neoplastic lesions associated with abnormal wound healing, including hypertrophic scars or dermal keloids (19, 20, 21). There are data suggesting that a wound healing response may induce DT formation (11, 12).…”

Section: Discussionmentioning

confidence: 99%

“…However, under conditions of chronic inflammation or tumor progression, these activated cells persist. For example, both MSCs and fibrocytes are found in keloids and hypertrophic scars (19, 20, 21). Together, these multipotent cells cooperate synergistically to support angiogenesis, a hallmark of accelerated wound healing and fibrosis (22, 23, 24).…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal Stromal Cell Mutations and Wound Healing Contribute to the Etiology of Desmoid Tumors

et al. 2012

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Desmoid tumors (DTs) are nonmalignant neoplasms of mesenchymal origin that mainly contain fibroblast lineage cells. These tumors often occur in Familial Adenomatous Polyposis Coli (FAP) patients who have germline mutations in the APC gene. Given emerging data that has implicated multipotent mesencyhmal stromal cells (MSCs) in the origin of mesenchymal tumors, we hypothesized that DTs may arise in FAP patients after MSCs acquire somatic mutations during the proliferative phase of wound healing. To test this idea, we examined 16 DTs from FAP-associated and sporadic cases, finding that all 16/16 tumors expressed stem cell markers whereas matching normal stromal tissues were uniformly negative. DTs also contained a subclass of fibrocytes linked to wound healing, angiogenesis and fibrosis. Using a MSC cell line derived from a FAP-associated DT, we confirmed an expected loss in the expression of APC and the transcriptional repressor BMI-1 while documenting the co-expression of markers for chondrocytes, adipocytes and osteocytes. Together, our findings argue that DTs result from the growth of MSCs in a wound healing setting that is associated with deregulated Wnt signaling due to APC loss. The differentiation potential of these MSCs combined with expression of BMI-1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggests that DTs may respond to therapies targeting these pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cell Mutations and Wound Healing Contribute to the Etiology of Desmoid Tumors

et al. 2012

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“…It was shown that hMSCs migration through the membrane pores of 8 lm in diameter was more efficient when the normal dermal fibroblasts were replaced by the keloid-derived ones on the bottom of a dual-modified Boyden chamber. The hMSCs were able to migrate across the membrane with 3 lm pores only when the same keloid-derived fibroblasts were placed on the bottom of the plates (Akino et al 2008). Similarly, the migration of hMSCs trough the 3 lm transwell membrane made from polyethylene terephthalate was effective and used for the wound healing test of human type II alveolar epithelial cell line on the opposite side of the same membrane (Akram et al 2013).…”

Section: Micrometric Pores For Cell-cell Interactionmentioning

confidence: 99%

Scaffolds and cells for tissue regeneration: different scaffold pore sizes—different cell effects

et al. 2015

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During the last decade biomaterial sciences and tissue engineering have become new scientific fields supplying rising demand of regenerative therapy. Tissue engineering requires consolidation of a broad knowledge of cell biology and modern biotechnology investigating biocompatibility of materials and their application for the reconstruction of damaged organs and tissues. Stem cell-based tissue regeneration started from the direct cell transplantation into damaged tissues or blood vessels. However, it is difficult to track transplanted cells and keep them in one particular place of diseased organ. Recently, new technologies such as cultivation of stem cell on the scaffolds and subsequently their implantation into injured tissue have been extensively developed. Successful tissue regeneration requires scaffolds with particular mechanical stability or biodegradability, appropriate size, surface roughness and porosity to provide a suitable microenvironment for the sufficient cell-cell interaction, cell migration, proliferation and differentiation. Further functioning of implanted cells highly depends on the scaffold pore sizes that play an essential role in nutrient and oxygen diffusion and waste removal. In addition, pore sizes strongly influence cell adhesion, cell-cell interaction and cell transmigration across the membrane depending on the various purposes of tissue regeneration. Therefore, this review will highlight contemporary tendencies in application of non-degradable scaffolds and stem cells in regenerative medicine with a particular focus on the pore sizes significantly affecting final recover of diseased organs.

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“…61 It has also been proposed that mesenchymal stem cells may participate in keloid pathogenesis by differentiating toward keloid formation and progression. 62 Thus, could the initiation of pathological scars relate to stem cell-like functions of keloid cells?…”

Section: Future Perspectivesmentioning

confidence: 99%

Keloids and Hypertrophic Scars

Huang

Murphy

Akaishi

et al. 2013

Plastic and Reconstructive Surgery Global Open

125

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Summary:The development of cutaneous pathological scars, namely, hypertrophic scars (HSs) and keloids, involves complex pathways, and the exact mechanisms by which they are initiated, evolved, and regulated remain to be fully elucidated. The generally held concepts that keloids and HSs represent “aberrant wound healing” or that they are “characterized by hyalinized collagen bundles” have done little to promote their accurate clinicopathological classification or to stimulate research into the specific causes of these scars and effective preventative therapies. To overcome this barrier, we review here the most recent findings regarding the pathology and pathogenesis of keloids and HSs. The aberrations of HSs and keloids in terms of the inflammation, proliferation, and remodeling phases of the wound healing process are described. In particular, the significant roles that the extracellular matrix and the epidermal and dermal layers of skin play in scar pathogenesis are examined. Finally, the current hypotheses of pathological scar etiology that should be tested by basic and clinical investigators are detailed. Therapies that have been found to be effective are described, including several that evolved directly from the aforementioned etiology hypotheses. A better understanding of pathological scar etiology and manifestations will improve the clinical and histopathological classification and treatment of these important lesions.

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Human mesenchymal stem cells may be involved in keloid pathogenesis

Abstract: The results of this study may indicate that human mesenchymal stem cells participate and recruit in keloid pathogenesis by differentiating themselves toward keloid recalcitrant formation and progression.

Cited by 28 publications

References 13 publications

Mesenchymal Stromal Cell Mutations and Wound Healing Contribute to the Etiology of Desmoid Tumors

Mesenchymal Stromal Cell Mutations and Wound Healing Contribute to the Etiology of Desmoid Tumors

Scaffolds and cells for tissue regeneration: different scaffold pore sizes—different cell effects

Keloids and Hypertrophic Scars

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