The cadaveric human skin allograft as a paradigm shift for the management of a large wound of necrotizing soft tissue infection: an interesting case report

Necrotizing soft tissue infection (NSTI) is an uncommon but fatal and rapidly progressing disease which requires emergent recognition and prompt treatment. Patients of NSTI frequently suffer from large soft tissue defects, which require coverage of these defects by auto-skin graft or flap cover. It becomes a challenge to cover the soft tissue defects in an already sick patient. The patient of NSTI has a restricted skin graft donor site and a poor skin grafting bed. Here authors report a case of 50 years old female, known case of type 2 diabetes mellitus, who suffered from NSTI post intramuscular injection of the left gluteal region. Her left thigh, left gluteal region, lower back, pubic and perineal region were involved. She underwent multiple radical debridement’s followed by the use of Cadaveric human skin allografts to cover the raw area temporarily. Meanwhile, authors optimized the patient nutrition state and controlled the infections. Finally, raw areas were covered with an autologous skin graft, and the patient discharged in stable condition.

Immunoregulation of allograft rejection: A role played by human CD200+ sub-population from human placenta-derived mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Immune rejection of skin allograft is a clinical problem to be solved. Our previous study has shown that human placenta-derived CD200+ mesenchymal stem cells may have a strong capability of immunoregulation. OBJECTIVE: To investigate the effects of human placenta-derived CD200+ mesenchymal stem cells on rejection of skin allograft. METHODS: Skin allograft models of c57/BL6 mice were established and divided into three groups as control group, human placenta-derived mesenchymal stem cells group (PMSCs group), and CD200+ mesenchymal stem cells group (CD200+-PMSCs group). PBS (control group), normal PMSCs and CD200+-PMSCs were injected into the mice through the tail vein, respectively. The necrotic time, survival time and situation of grafted skin were observed. The number of peripheral white blood cells was counted after 7 days of treatment. The expression levels of interleukin-10, interferon-γ and tumor necrosis factor-α were detected by Q-PCR and ELISA. RESULTS AND CONCLUSION: (1) Compared with the control group, in the PMSCs and CD200+-PMSCs groups, the condition of skin allograft was better, and the survival time was significantly prolonged (P < 0.001). The condition and survival time of skin allograft in the CD200+-PMSCs group were significantly superior to those in the PMSCs group (P < 0.01). (2) After 7 days of treatment, the number of peripheral white blood cells in the PMSCs and CD200+-PMSCs groups was significantly less than that in the control group (P < 0.01). (3) Compared with the control group, the mRNA expression level of interleukin-10 in the spleen was significantly increased in the CD200+-PMSCs group (P < 0.05), and the mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen were significantly down-regulated in the PMSCs and CD200+-PMSCs groups (P < 0.05, P < 0.01). The mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.01, P < 0.05). (4) Compared with the control group, the expression level of interleukin-10 in the blood was significantly increased (P < 0.05, P < 0.001), and the expression levels of interferon-γ and tumor necrosis factor-α in the blood were significantly down-regulated in the CD200+-PMSCs and PMSCs groups (P < 0.05, P < 0.001; P < 0.01, P < 0.001). The expression levels of interferon-γ and tumor necrosis factor-α in the blood in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.05). These results indicate that human placenta-derived mesenchymal stem cells have immunosuppressive effect on the rejection of skin allograft, and CD200+ cells may have better immunoregulatory effects by regulating the expressions of interleukin-10, interferon-γ and tumor necrosis factor-α

Cadaveric donor skin allograft as a temporary dressing material in the management of complicated wounds

Introduction: Wounds resulting from various causes are the most common health problem in developing countries like India. Management of these wound is very difficult, requiring longer hospital stay, loss of income, psychological problems like depression. In our study, we used cadaveric donor skin as a temporary dressing material for wound cover and see the outcome of definitive splitthickness skin graft following cadaveric donor skin application. Previously cadaveric skin was used for covering the burns wound. Only very few studies are available regarding the use of cadaveric donor skin in the management of complicated wounds. Materials and methods: This was a prospective, non-randomized, uncontrolled study conducted in the Department of General Surgery, Government Stanley Medical College Hospital from October 2017 to September 2018. Once the wound scheduled for cadaveric grafting, the cadaveric skin was meshed in the laminar flow cabinet, the skin was washed in the normal saline, to ensure that all the preservative fluid had been removed. The skin is transported in a sterile container. The cadaveric graft was applied to the wound. No fixation done. Limb was immobilized using POP. Sterile was dressing done. Results: In our study 44 patients underwent cadaveric donor skin grafting. In 40 out of 44 patients (90.9%), the cadaveric donor skin had good take. All 40 patients underwent definitive split-thickness skin grafting. The mean graft take was 90.35%, with maximum graft take was 96% and minimum graft take was 82%. The standard deviation was 3.512%. When reviewing the literature which showed the success rate of STSG was 78% at closing 90% of the wound by 8 weeks. In our study, the mean duration of hospital stay was 34.2 days, with maximum of 57 days and a minimum of 17 days. Most Jim Jebakumar, S. Ranjith Kumar. Cadaveric donor skin allograft as a temporary dressing material in the management of complicated wounds. IAIM, 2019; 6(3): 65-72. Page 66 of the wounds required only single cadaveric graft application, 37 (84.1%) out of 44 patients and 7 patients (15.9%) required more than one cadaveric donor skin grafting. Conclusion: By this study, we can able to minimize the expenses by using the cadaveric skin to predict the success of definitive split-thickness skin grafting. We can also minimize the duration of hospital stay and prolonged use of antibiotics if the cadaveric skin take is successful.

Effect of extracorporeal photochemotherapy on the regulatory T cells in mice with skin allograft Wei / 器官移植

Objective To investigate the effect of infusion of spleen lymphocytes treated by extracorporeal photochemotherapy on the regulatory T cell (Treg)and survival time of skin allograft in mice. Methods The skin allograft model in mice was established with C57BL/6 mice as donors and BALB/c mice as recipients. The spleen lymphocytes (CSP,BSP)in mice C57BL/6 and BALB/c were isolated,and the mice spleen lymphocytes (PUVA-SP) treated with 8-methoxypsoralen plus ultraviolet (PUVA)were prepared. The experimental animals were randomly divided into 5 groups according to the compositions infused into the recipients through vein:PUVA-BSP,PUVA-CSP,BSP,CSP and phosphate buffer solution (PBS)control groups (n=12 in each group). All recipients of each group were injected with PUVA-BSP,PUVA-CSP,BSP,CSP or PBS on day 7 before the operation,on the operation day and day 7 after the operation through the tail vein,respectively. The survival time of graft in the recipients was observed,and the expression of CD4 +CD25 +Foxp3 +Treg in peripheral blood was detected. Results After skin allograft,the rate of CD4 +CD25 +Foxp3 +Treg in peripheral blood of the recipients in PUVA-BSP group and PUVA-CSP group was significantly higher than those of BSP, CSP and PBS control groups. The rate of CD4 +CD25 +Foxp3 +Treg in PUVA-CSP group was higher than that of PUVA-BSP group,while BSP and CSP groups were lower than that of PBS control group. The survival time of skin graft in the recipients in PUVA-BSP group and PUVA-CSP group was significantly longer than that of BSP,CSP and PBS control groups (all P<0.05 ). Conclusions Sufficient infusion of PUVA-SP can induce more CD4 +CD25 +Foxp3 +Treg in the recipients and prolong survival time of skin graft significantly.

Estudo comparativo dos efeitos da talidomida, da ciclosporina e do diclofenaco na sobrevida de aloenxertos cutâneos em coelho / Assessment of immunossupresion induced by thalidomide, cyclosporine and diclofenac on skin allograft survival in rabbits

OBJETIVO: Verificar se a talidomida é capaz de evitar a rejeição de aloenxertos de pele em coelhos, como droga isolada, ou melhorar a eficácia de doses subterapêuticas de ciclosporina, comparando seu efeito ao de doses terapêuticas da ciclosporina e também ao papel antiinflamatório do diclofenaco de sódio. MÉTODOS: Foram estudados 42 coelhos, distribuídos nos seguintes grupos (n=6): Grupo 1 - controle com auto-enxerto; Grupo 2 - controle com aloenxerto; Grupo 3 - aloenxerto sob o efeito de talidomida (100 mg/kg/dia); Grupo 4 - aloenxerto sob o efeito de diclofenaco de sódio (2 mg/kg/dia); Grupo 5 - aloenxerto sob o efeito de ciclosporina (10 mg/kg/dia); Grupo 6 - aloenxerto sob o efeito de ciclosporina (5 mg/kg/dia); Grupo 7 - aloenxerto sob o efeito de ciclosporina (5 mg/kg/dia) associada a talidomida (100 mg/kg/dia). Foram retirados enxertos circulares de pele total do dorso de uma das orelhas do animal. Os medicamentos foram administrados por cateter orogástrico, a partir do dia anterior ao transplante. Os enxertos foram trocados entre coelhos de raças diferentes. RESULTADOS: A ciclosporina a 10 mg/kg/dia prolongou a sobrevida dos enxertos de pele, sendo seu efeito comparável ao obtido com a ciclosporina em dose subterapêutica (5 mg/kg/dia) associada a talidomida a 100 mg/kg/dia. A talidomida isoladamente, mesmo em concentração de 100 mg/kg/dia, e o diclofenaco tiveram efeito mínimo na sobrevida média dos aloenxertos cutâneos. O número de eosinófilos no infiltrado inflamatório circunjacente à necrose foi maior nos grupos tratados com diclofenaco e com ciclosporina a 5 mg/kg/dia e menor no grupo em que se associou ciclosporina com talidomida. CONCLUSÃO: A talidomida pode ser uma droga útil para associar-se a baixas doses de ciclosporina no tratamento de aloenxertos cutâneos.

OBJECTIVE: Allografting is one of the therapeutic alternatives for extensive burn victims without sufficient skin donor areas. This research studied the effects of cyclosporine, as an immunosuppressor model, and thalidomide and dyclofenac as anti-inflammatory drugs on an experimental skin allograft research. METHODS: Forty-two rabbits were divided in the following groups (n=6): Group 1 - autografting control; Group 2 - allografting control; Group 3 - allografts under thalidomide effect (100 mg/kg/day); Group 4 - allografts under sodium dyclofenac effect (2 mg/kg/day); - Group 5 -allografts under cyclosporine effect (10 mg/kg/day); Group 6 - allografts under cyclosporine effect (5 mg/kg/day); Group 7- allografts under cyclosporine (5 mg/kg/day) plus thalidomide (100 mg/kg/day) effect. Drugs were given via orogastric tube since the day before transplantation and daily during the postoperative period. Circular total skin grafts of the ear were exchanged between California and White New Zealand rabbits. RESULTS: Cyclosporine 10 mg/kg/day increased allograft survival and this effect was comparable to the association of cyclosporine 5 mg/kg/day with thalidomide 100 mg/kg/day. Thalidomide as an isolated drug and dyclofenac had a minimum effect on the average survival of the skin allografts. The number of eosinophils around the necrotic skin was higher in the dyclofenac group and lower in the group receiving cyclosporine associated with thalidomide. CONCLUSION: This study showed that thalidomide may be an useful drug when associated with subtherapeutic doses of cyclosporine for treatment of skin allografts.

The Effect of Donor Antigen-pulsed Dendritic Cells on Survival of Skin Allograft in a Rat Model

PURPOSE: Prevention of acute rejection in skin allografts without continuous immunosuppression lacks reports in worldwide literature. Needs for chronic immunosuppression preclude the use of tissue allograft as a routine surgical reconstructive option. Recently dendritic cells(DC) gained considerable attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effects of alloantigen-pulsed dendritic cells in induction of survival increase in a rat skin allograft model. METHODS: Recipient-derived dendritic cells were harvested from rat whole blood and cultured with GM- CSF(200ng/mL) and IL-4(8ng/mL) for 2 weeks. Then donor-specific alloantigen pulsed dendritic cells were reinjected into tail vein before skin graft. The rat dorsal skin allografts were transplanted in 5 subgroups. Groups: I) untreated, II) anti-lymphocyte serum(ALS, 0.5 mL), III) FK-506(2mg/kg), IV) DCp, VI) DCp and FK- 506. Graft appearance challenges were assessed postoperatively. RESULTS: The group V(DC and FK-506 treated) showed longest graft survival rate(23.5 days) than other groups; untreated(5.8 days), ALS(7.2 days), FK-506 (17.5 days), DCp(12.2 days). CONCLUSION: Donor antigen pulsed host dendritic cell combined with short-term immunosuppression prolong skin allograft survival and has potential therapeutic application for induction of donor antigen specific tolerance.

PROLONGATION OF SKIN ALLOGRAFT SURVIVAL BY TOPICAL USE OF CYC-LOSPORINE A (CsA) / 解放军医学杂志

A long course of systemic treatment with CsA in therapeutic dose to prolong skin allografts may produce severe toxic effects,therefore it is not acceptable for severe burn patients.Prior studies by one of us have reported that topical treatment with CsA will prolong the life of allografts.During the period of treatment,however,blood CsA levels were detected in high concentrations,similar to systemic use.The question occurs whether the immunosuppressive effect of topically applied CsA was due to local or systemic action.Two experiments were carried out.First,two skin grafts of ACI (RT1) ratswere transplanted on both sides of the back of same LEW (RT1) rat (n=56).The bandage was kept on for the first 5 postoperative days.One graft was treated topically daily with CsA 7.5mg/day in olive oil until rejection.At the same time,the other side was treated with olive oil alone as control.,The mean survival time (MST) was 12.38?0.70 and 9.14?0.33 d.,respectively,p