<i>In vitro</i> differentiation of human mesenchymal stem cells to epithelial lineage

Păunescu, Virgil; Deak, Erika; Herman, Diana; Siska, Ioana Raluca; ̆anasie, Gabriela T; Bunu, Carmen; Anghel, S.; Tatu, Calin A.; Oprea, Tudor I.; Henschler, Reinhard; Rüster, Brigitte; Bistrian, Roxana; Seifried, Erhard

doi:10.1111/j.1582-4934.2007.00041.x

Cited by 146 publications

(111 citation statements)

References 28 publications

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“…18 For example, the propensity of stromal cell populations to promote tissue healing has been shown in the settings of lung, brain, heart, and kidney injury. [19][20][21][22] It has also been shown that cells in the marrow are capable of differentiation into the epithelial lineage 23,24 and that after hematopoietic cell transplantation these cells are able to engraft in the skin of the recipient, especially in sites affected by graft-versus-host disease. 25 Finally, directly or systemically administered BM cells have been shown to promote healing of skin wounds, 26,27 which are the hallmark of RDEB.…”

Section: Introductionmentioning

confidence: 99%

Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells

Tolar

Ishida‐Yamamoto

Riddle

et al. 2009

Blood

151

135

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The recessive dystrophic form of epidermolysis bullosa (RDEB) is a disorder of incurable skin fragility and blistering caused by mutations in the type VII collagen gene (Col7a1). The absence of type VII collagen production leads to the loss of adhesion at the basement membrane zone due to the absence of anchoring fibrils, which are composed of type VII collagen. We report that wild-type, congenic bone marrow cells homed to damaged skin, produced type VII collagen protein and anchoring fibrils, ameliorated skin fragility, and reduced lethality in the murine model of RDEB generated by targeted Col7a1 disruption. These data provide the first evidence that a population of marrow cells can correct the basement membrane zone defect found in mice with RDEB and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders. IntroductionEpidermolysis bullosa represents a family of severe, lifethreatening skin disorders resulting from mutations in genes encoding protein components of the cutaneous basement membrane zone. Although some forms, such as the junctional type, are lethal in the neonatal period, others, such as the dystrophic forms, lead to years of painful skin blistering and mutilating scarring. The most severe form of dystrophic epidermolysis bullosa (the Hallopeau-Siemens type) is caused by recessive mutations in the type VII collagen gene (Col7A1). 1 The recessive dystrophic form of epidermolysis bullosa (RDEB) is characterized by severely diminished type VII collagen (col7) production. 2 The homotrimeric col7 protein is synthesized by fibroblasts and keratinocytes and represents the key component of anchoring fibrils that connect cutaneous basement membrane to the dermal matrix. 3 Severe attenuation of anchoring fibrils in RDEB results in impaired dermal-epidermal cohesion and diminished adhesion of gastrointestinal mucosa at the basement membrane zone. Compromised integrity of the stratifying squamous epithelia leads to increased cutaneous and mucosal sensitivity to mechanical stress and stigmatizing, and to an eventually lethal, clinical phenotype. Children with RDEB develop painful skin and mucosal blistering, mutilating scarring, alopecia, corneal erosions, tooth decay, esophageal strictures, anemia, joint contractures, small epidermal inclusion cysts (milia), nail dystrophy, and fusion of fingers and toes (pseudosyndactyly or "mitten" deformity) by the age of 6 to 8 years. As a result of extreme skin fragility, aberrant tissue repair, and chronic inflammation, RDEB patients develop squamous cell carcinomas in the third decade of life. 4 At this time, there is no therapeutic intervention with proven curative benefit. Palliative measures include complex bandaging of most of the body surface (to protect the skin from the slightest friction, and to prevent infection and excessive loss of body fluid), surgical debridement and analgesia, and nutritional support (using liquid or pureed food by mouth or via percutaneous gastric feeding tube) and analgesia. Faced wit...

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Section: Introductionmentioning

confidence: 99%

Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells

Tolar

Ishida‐Yamamoto

Riddle

et al. 2009

Blood

151

135

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“…Recently, there have also been significant advances in the use of autologous mesenchymal stem cells to regenerate human tissues [28,29]. It has been reported that MSC express markers pertaining to corneal epithelial stem cells [30][31][32][33] and can be induced to differentiate to epithelial like cells both in vitro and in vivo [33][34][35][36]. A critical factor in mesenchymal stem cell biology is to propagate cells with suitable stem cell characteristics, multipotency and high proliferative potential for its use in various biomedical applications.…”

Section: Discussionmentioning

confidence: 99%

Standardizing transdifferentiation of rabbit bone marrow mesenchymal stem cells to corneal lineage by simulating corneo-limbal cues

Mathews¹,

Prasad²,

Venugopa³

et al. 2017

J Stem Cell Res Med

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Corneal pathologies due to limbal stem cell deficiency or trauma is a common occurrence with high incidence in the modern era. Absence of native limbal stem cells in these cases can even result in blindness unless treated. Identifying alternate autologous stem cells with potential to replace limbal stem cells, gain its significance especially in cases of bilateral limbal damage. Here we look at the suitability of proposing bone marrow derived mesenchymal stem cells as an alternate to limbal stem cells. This work had made use of the corneo -limbal cues for trans differentiating these mesodermal cells to corneal epithelial lineage. Mesenchymal stem cells were isolated from rabbit bone marrow and the culture conditions were optimized. Characterized mesenchymal stem cells were transdifferentiated by simulating limbal niche using extracellular matrix and limbal fibroblast conditioned medium. The differentiation to corneal lineage was evaluated by analyzing the expression of mesenchymal (ABCG2, CD29) and corneal epithelial (CK3/12) markers. Cells cultured in the presence of conditioned medium alone and with conditioned medium/ extracellular matrix showed the expression of CK3/12. CK3/12 expressing cells in these cultures were increasing, with a concomitant decrease in stem cell marker expression. Trans differentiating mesenchymal stem cells to corneal epithelial like cells will provide a useful, autologous source of adult stem cells in therapeutic approaches for patients suffering from bilateral limbal stem cell deficiency.

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“…First, MSCs are able to differentiate toward fibroblasts, endothelial cells, and keratinocytes. 45,46 However, accumulating evidence suggests that MSCs are recruited and mobilized from distant sites toward the wound. Injury per se increases the levels of circulating MSCs in peripheral circulation.…”

Section: Mscs In Skin and During Wound Healingmentioning

confidence: 99%

Do Mesenchymal Stem Cells Have a Role to Play in Cutaneous Wound Healing?

Pountos¹,

Panteli²,

Georgouli³

et al. 2014

CTTT

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Cutaneous wounds represent a significant healthcare problem despite our increasing understanding of the molecular and cellular events governing this process. A major contributor to this problem is the lack of reliable therapies for the treatment of "hard-to-heal" wounds. Tissue engineering with the use of mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool with favorable early experimental and clinical results. This manuscript aims to provide an overview of the available approaches to up-regulate the cutaneous wound response with the use of MSCs.

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In vitro differentiation of human mesenchymal stem cells to epithelial lineage

Cited by 146 publications

References 28 publications

Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells

Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells

Standardizing transdifferentiation of rabbit bone marrow mesenchymal stem cells to corneal lineage by simulating corneo-limbal cues

Do Mesenchymal Stem Cells Have a Role to Play in Cutaneous Wound Healing?

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