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The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study.

El Sadik AO, El Ghamrawy TA, Abd El-Galil TI - PLoS ONE (2015)

Bottom Line: Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds.Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups.MSCs enhanced the healing process of wound closure more than chitosan gel treatment.

View Article: PubMed Central - PubMed

Affiliation: Anatomy and Embryology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

ABSTRACT

Background: Wound healing involves the integration of complex biological processes. Several studies examined numerous approaches to enhance wound healing and to minimize its related morbidity. Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds. The aim of the current work was to compare MSCs versus chitosan in wound healing, evaluate the most efficient route of administration of MSCs, either intradermal or systemic injection, and elicit the mechanisms inducing epidermal and dermal cell regeneration using histological, immunohistochemical and fluorescent techniques.

Material and methods: Forty adult male Sprague Dawley albino rats were divided into four equal groups (ten rats in each group): control group (Group I); full thickness surgical skin wound model, Group II: Wound and chitosan gel. Group III: Wound treated with systemic injection of MSCs and Group IV: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 3, 5, 10 and 15 for gross morphological evaluation and on day 10 and 15 for histological, immunohistochemical and fluorescent studies.

Results: Chitosan was proved to promote wound healing more than the control group but none of their wound reached complete closure. Better and faster healing of wounds in MSCs treated groups were manifested more than the control or chitosan treated groups. It was found that the intradermal route of administration of stem cells enhanced the rate of healing of skin wounds better than the systemic administration to the extent that, by the end of the fifteenth day of the experiment, the wounds were completely healed in all rats of this group. Histologically, the wound areas of group IV were hardly demarcated from the adjacent normal skin and showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups.

Conclusion: MSCs enhanced the healing process of wound closure more than chitosan gel treatment. Furthermore, MSCs injected intradermally, were more efficient in accelerating wound healing than any other mode of treatment.

No MeSH data available.


Related in: MedlinePlus

Photomicrographs of the skin wound area on the 15th day.a,b) control group showing the wound area covered by regenerated epidermis. The regenerated dermis was filled with inflammatory cell infiltrates and many congested blood vessels with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. c,d) Group II showing the wound covered by regenerated epidermis on the granulation tissue in the regenerated dermis with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. Mild inflammatory cell infiltrates appeared in the dermis of the wound bed and congested blood vessels. e,f) Group III and g,h) Group IV wound area showing complete regeneration of the epidermis and dermis. The regenerated dermis showed fully regenerated hair follicles and sebaceous glands with absence of inflammatory cells and congested vessels. Connective tissue bundles were arranged in different directions. GT: granulation tissue, E: epidermis, D: dermis, H: hypodermis, M: muscle fibers, F: hair follicles, S: sebaceous gland, I: inflammatory cell infiltrate, B: collagen bundles, thick arrow: junction between the normal skin and the wound area, V: blood vessel, (H&E, a-c-e-g x100; b-d-f-h x400)
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pone.0137544.g002: Photomicrographs of the skin wound area on the 15th day.a,b) control group showing the wound area covered by regenerated epidermis. The regenerated dermis was filled with inflammatory cell infiltrates and many congested blood vessels with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. c,d) Group II showing the wound covered by regenerated epidermis on the granulation tissue in the regenerated dermis with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. Mild inflammatory cell infiltrates appeared in the dermis of the wound bed and congested blood vessels. e,f) Group III and g,h) Group IV wound area showing complete regeneration of the epidermis and dermis. The regenerated dermis showed fully regenerated hair follicles and sebaceous glands with absence of inflammatory cells and congested vessels. Connective tissue bundles were arranged in different directions. GT: granulation tissue, E: epidermis, D: dermis, H: hypodermis, M: muscle fibers, F: hair follicles, S: sebaceous gland, I: inflammatory cell infiltrate, B: collagen bundles, thick arrow: junction between the normal skin and the wound area, V: blood vessel, (H&E, a-c-e-g x100; b-d-f-h x400)

Mentions: On the fifteenth day, the control group (group I) and chitosan gel treated group (group II) showed regenerated epidermis covering the wound surface. The regenerated dermis of both groups showed congested blood vessels with absence of hair follicles and sebaceous glands (Fig 2a and 2c). The dermis of the wound bed was filled with inflammatory cell infiltrate and many congested blood vessels in the control group (Fig 2b), while it expressed mild inflammatory cell infiltrate and congested blood vessels in chitosan gel treated group (group II) (Fig 2d). The wound area in MSCs systemically treated group (group III) revealed complete regeneration of the epidermis with newly regenerated hair follicles (Fig 2e). The connective tissue bundles were loosely arranged in many directions in the dermis (Fig 2f). In group IV (intradermally injected MSCs), the wound area was hardly demarcated from the adjacent normal skin. The wound area showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. The regenerated dermis showed fully regenerated hair follicles and sebaceous glands (Fig 2g). Connective tissue bundles were arranged in many directions surrounding fully regenerated hair follicles and sebaceous glands in the dermis (Fig 2h).


The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study.

El Sadik AO, El Ghamrawy TA, Abd El-Galil TI - PLoS ONE (2015)

Photomicrographs of the skin wound area on the 15th day.a,b) control group showing the wound area covered by regenerated epidermis. The regenerated dermis was filled with inflammatory cell infiltrates and many congested blood vessels with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. c,d) Group II showing the wound covered by regenerated epidermis on the granulation tissue in the regenerated dermis with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. Mild inflammatory cell infiltrates appeared in the dermis of the wound bed and congested blood vessels. e,f) Group III and g,h) Group IV wound area showing complete regeneration of the epidermis and dermis. The regenerated dermis showed fully regenerated hair follicles and sebaceous glands with absence of inflammatory cells and congested vessels. Connective tissue bundles were arranged in different directions. GT: granulation tissue, E: epidermis, D: dermis, H: hypodermis, M: muscle fibers, F: hair follicles, S: sebaceous gland, I: inflammatory cell infiltrate, B: collagen bundles, thick arrow: junction between the normal skin and the wound area, V: blood vessel, (H&E, a-c-e-g x100; b-d-f-h x400)
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Related In: Results  -  Collection

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pone.0137544.g002: Photomicrographs of the skin wound area on the 15th day.a,b) control group showing the wound area covered by regenerated epidermis. The regenerated dermis was filled with inflammatory cell infiltrates and many congested blood vessels with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. c,d) Group II showing the wound covered by regenerated epidermis on the granulation tissue in the regenerated dermis with absence of hair follicles and sebaceous glands. The adjacent normal skin showed hair follicles and sebaceous gland. Mild inflammatory cell infiltrates appeared in the dermis of the wound bed and congested blood vessels. e,f) Group III and g,h) Group IV wound area showing complete regeneration of the epidermis and dermis. The regenerated dermis showed fully regenerated hair follicles and sebaceous glands with absence of inflammatory cells and congested vessels. Connective tissue bundles were arranged in different directions. GT: granulation tissue, E: epidermis, D: dermis, H: hypodermis, M: muscle fibers, F: hair follicles, S: sebaceous gland, I: inflammatory cell infiltrate, B: collagen bundles, thick arrow: junction between the normal skin and the wound area, V: blood vessel, (H&E, a-c-e-g x100; b-d-f-h x400)
Mentions: On the fifteenth day, the control group (group I) and chitosan gel treated group (group II) showed regenerated epidermis covering the wound surface. The regenerated dermis of both groups showed congested blood vessels with absence of hair follicles and sebaceous glands (Fig 2a and 2c). The dermis of the wound bed was filled with inflammatory cell infiltrate and many congested blood vessels in the control group (Fig 2b), while it expressed mild inflammatory cell infiltrate and congested blood vessels in chitosan gel treated group (group II) (Fig 2d). The wound area in MSCs systemically treated group (group III) revealed complete regeneration of the epidermis with newly regenerated hair follicles (Fig 2e). The connective tissue bundles were loosely arranged in many directions in the dermis (Fig 2f). In group IV (intradermally injected MSCs), the wound area was hardly demarcated from the adjacent normal skin. The wound area showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. The regenerated dermis showed fully regenerated hair follicles and sebaceous glands (Fig 2g). Connective tissue bundles were arranged in many directions surrounding fully regenerated hair follicles and sebaceous glands in the dermis (Fig 2h).

Bottom Line: Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds.Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups.MSCs enhanced the healing process of wound closure more than chitosan gel treatment.

View Article: PubMed Central - PubMed

Affiliation: Anatomy and Embryology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

ABSTRACT

Background: Wound healing involves the integration of complex biological processes. Several studies examined numerous approaches to enhance wound healing and to minimize its related morbidity. Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds. The aim of the current work was to compare MSCs versus chitosan in wound healing, evaluate the most efficient route of administration of MSCs, either intradermal or systemic injection, and elicit the mechanisms inducing epidermal and dermal cell regeneration using histological, immunohistochemical and fluorescent techniques.

Material and methods: Forty adult male Sprague Dawley albino rats were divided into four equal groups (ten rats in each group): control group (Group I); full thickness surgical skin wound model, Group II: Wound and chitosan gel. Group III: Wound treated with systemic injection of MSCs and Group IV: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 3, 5, 10 and 15 for gross morphological evaluation and on day 10 and 15 for histological, immunohistochemical and fluorescent studies.

Results: Chitosan was proved to promote wound healing more than the control group but none of their wound reached complete closure. Better and faster healing of wounds in MSCs treated groups were manifested more than the control or chitosan treated groups. It was found that the intradermal route of administration of stem cells enhanced the rate of healing of skin wounds better than the systemic administration to the extent that, by the end of the fifteenth day of the experiment, the wounds were completely healed in all rats of this group. Histologically, the wound areas of group IV were hardly demarcated from the adjacent normal skin and showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups.

Conclusion: MSCs enhanced the healing process of wound closure more than chitosan gel treatment. Furthermore, MSCs injected intradermally, were more efficient in accelerating wound healing than any other mode of treatment.

No MeSH data available.


Related in: MedlinePlus