Cell-based therapy for epithelial wounds

Harris, David T.; Hilgaertner, Jianhua W.; Simonson, Caitlin; Ablin, Richard J.; Badowski, Michael

doi:10.3109/14653249.2012.671520

Cited by 7 publications

(5 citation statements)

References 30 publications

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“…We and others have also observed that hWJSCs readily differentiate into keratinocytes in vitro using two conventional differentiation protocols [Schneider et al, ; Jin et al, ]. Cell proliferation is essential in the regenerative phase of wound healing and apart from the dermal fibroblasts and keratinocytes, the stem, or progenitor cells within the skin niches are also involved in cell turnover [Harris et al, ]. Our results are consistent with the findings of Shin and Peterson [] that the introduction of soluble bioactive molecules into wounds via the hWJSC‐CM and secretion of the same molecules by the engrafted GFP‐hWJSCs creates a niche for the recruitment of native skin MSCs and progenitor cells to the wound site to facilitate healing.…”

Section: Discussionsupporting

confidence: 90%

Human Wharton's Jelly Stem Cells and Its Conditioned Medium Enhance Healing of Excisional and Diabetic Wounds

Fong

Tam

Cheyyatraivendran

et al. 2013

J of Cellular Biochemistry

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Wound healing is a major problem in diabetic patients and current treatments have met with limited success. We evaluated the treatment of excisional and diabetic wounds using a stem cell isolated from the human umbilical cord Wharton's jelly (hWJSC) that shares unique properties with embryonic and adult mesenchymal stem cells. hWJSCs are non-controversial, available in abundance, hypo-immunogenic, non-tumorigenic, differentiate into keratinocytes, and secrete important molecules for tissue repair. When human skin fibroblasts (CCD) in conventional scratch-wound assays were exposed to hWJSC-conditioned medium (hWJSC-CM) the fibroblasts at the wound edges migrated and completely covered the spaces by day 2 compared to controls. The number of invaded cells, cell viability, total collagen, elastin, and fibronectin levels were significantly greater in the hWJSC-CM treatment arm compared to controls (P < 0.05). When a single application of green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs) or hWJSC-CM was administered to full-thickness murine excisional and diabetic wounds, healing rates were significantly greater compared to controls (P < 0.05). Wound biopsies collected at various time points showed the presence of green GFP-labeled hWJSCs, positive human keratinocyte markers (cytokeratin, involucrin, filaggrin) and expression of ICAM-1, TIMP-1, and VEGF-A. On histology, the GFP-hWJSCs and hWJSC-CM treated wounds showed reepithelialization, increased vascularity and cellular density and increased sebaceous gland and hair follicle numbers compared to controls. hWJSCs showed increased expression of several miRNAs associated with wound healing compared to CCDs. Our studies demonstrated that hWJSCs enhance healing of excisional and diabetic wounds via differentiation into keratinocytes and release of important molecules.

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Section: Discussionsupporting

confidence: 90%

Human Wharton's Jelly Stem Cells and Its Conditioned Medium Enhance Healing of Excisional and Diabetic Wounds

Fong

Tam

Cheyyatraivendran

et al. 2013

J of Cellular Biochemistry

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“…Many studies have shown a benefit in the use of mesenchymal stromal cells in accelerating wound closure [3, 5, 7, 35, 36]. Our data using ADSCs delivered topically in stiff fibrin gels onto full thickness wounds show a clear benefit of ADSC cell delivery versus fibrin only or no treatment of the wound.…”

Section: Discussionmentioning

confidence: 57%

Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo

Mendez¹,

Ghaedi²,

Sivarapatna³

et al. 2015

Biomaterials

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Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs.

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“…Since, multipotent MSCs are easily expandable in culture and differentiate into multiple tissue lineages; there has been much interest in their clinical potential for tissue repair and gene therapy 103. Harris et al 104 study has given the idea regarding the use of bone marrow-derived cells (BMDC) comprising stroma, stem and progenitor cells, may contribute a significant part of regenerating epithelial tissue. They found that a single injection into the wound margin is sufficient to reverse the wounding process and promote normal wound healing.…”

Section: Stem Cells From Other Originmentioning

confidence: 99%

Stem Cell Research: A Novel Boulevard towards Improved Bovine Mastitis Management

Sharma

Jeong

2013

Int. J. Biol. Sci.

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The dairy industry is a multi-billion dollar industry catering the nutritional needs of all age groups globally through the supply of milk. Clinical mastitis has a severe impact on udder tissue and is also an animal welfare issue. Moreover, it significantly reduces animal value and milk production. Mammary tissue damage reduces the number and activity of epithelial cells and consequently contributes to decreased milk production. The high incidence, low cure rate of this highly economic and sometimes deadly disease is an alarming for dairy sector as well as policy makers. Bovine mammary epithelial cells (MECs) and their stem cells are very important in milk production and bioengineering. The adult mammary epithelium consists of two main cell types; an inner layer of luminal epithelial cells, which produce the milk during lactation, and an outer layer of myoepithelial cells resting on a basement membrane, which are responsible for pushing the milk through the ductal network to the teat cistern. Inner layer of columner/luminal cells of bovine MECs, is characterized by cytokeratin18, 19 (CK18, CK19) and outer layer such as myoepithelial cells which are characterized by CK14, α-smooth muscle actin (α-SMA) and p63. Much work has been done in mouse and human, on mammary gland stem cell research, particularly in cancer therapy, but stem cell research in bovine is still in its infancy. Such stem/progenitor cell discoveries in human and mouse mammary gland bring some hope for application in bovines. These progenitors may be therapeutically adopted to correct the structural/cytological defects in the bovine udder due to mastitis. In the present review we focused on various kinds of stem/progenitor cells which can have therapeutic utility and their possibilities to use as a potential stem cell therapy in the management of bovine post-mastitis damage in orders to restore milk production. The possibilities of bovine mammary stem cell therapy offers significant potential for regeneration of tissues that can potentially replace/repair diseased and damaged tissue through differentiation into epithelial, myoepithelial and/or cuboidal/columnar cells in the udder with minimal risk of rejection and side effects.

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Cell-based therapy for epithelial wounds

Cited by 7 publications

References 30 publications

Human Wharton's Jelly Stem Cells and Its Conditioned Medium Enhance Healing of Excisional and Diabetic Wounds

Human Wharton's Jelly Stem Cells and Its Conditioned Medium Enhance Healing of Excisional and Diabetic Wounds

Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo

Stem Cell Research: A Novel Boulevard towards Improved Bovine Mastitis Management

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