The Immunomodulatory Effect of Adipose-Derived Stem Cells in Xenograft Transplantation Model

Adipose-derived stem cells (ASCs) have demonstrated immunomodulatory and anti-inflammatory effects in preclinical studies. The purpose of this study was to evaluate the effects of ASCs on the survival of xenogeneic full-thickness skin grafts and compare intravenous and subcutaneous injections of ASCs.We divided 30 male C57BL/6 mice into control, intravenous (IV), and subcutaneous (SC) injection groups. In one group of 10 mice, mouse ASCs were intravenously injected after human full-thickness skin grafting (IV group). In another group of 10 mice, ASCs were directly injected into the subcutaneous plane under the xenogeneic grafts (SC group). An additional group of 10 mice received no treatment and served as controls. Bioluminescent imaging showed that ASCs were concentrated at the grafts during the study period in both IV and SC groups. We performed graft survival assessment, histologic examination, and immunohistochemistry analysis.ASCs significantly prolonged xenograft survival at postoperative week 2 in the SC group compared with the control group (P < .05). Histologic evaluation revealed fewer inflammatory reactions in the SC group than in the control group at 1 week posttransplantation. In addition, we observed relative reduction in CD4- and CD8-positive cells in the SC group compared with the control group. Intravenous injection of ASCs led to increased graft survival and decreased inflammatory reactions, but these differences were not statistically significant.The results of this study indicate that subcutaneous injection of ASCs promoted the survival of xenogeneic full-thickness skin grafts in mice. The underlying mechanisms of the immunosuppressive effects of ASCs should be further investigated.     

Prolongation of skin allograft survival by combined feeding of donor spleen cells and cyclosporine in mice

BACKGROUND: Oral immune tolerance is a method for inducing donor-specific immunotolerance and prolonging graft survival. OBJECTIVES: We studied the effect of feeding donor spleen cells in combination with cyclosporine (CsA) on skin allograft survival in mice. METHODS: Tail skins from BALB/c (H-2d) female mice were transplanted onto C57BL/6 (H-2b) female mice. The animals were divided into four groups, each with eight mice: group I, untreated controls; group II, treated with spleen cells; group III, treated with CsA; and group IV, treated with spleen cells and CsA. All grafts were inspected daily. Rejection was diagnosed when the graft loss was >80% to 90%. The immune responses of C57BL/6 toward donor mice were examined by delayed-type hypersensitivity (DTH). RESULTS: Survival times of allogeneic skin grafts in groups I, II, III, and IV were 9.9 +/- 0.6, 13.1 +/- 0.6, 14.7 +/- 0.9, and 20.0 +/- 0.7 days, respectively. When compared with group I, the survival times of groups II, III, and IV were prolonged significantly (P < .01). The survival time for group IV was prolonged significantly compared with groups II and III (P < .01). The DTH responses of group IV were decreased significantly in contrast to groups II and III (P < .01). CONCLUSIONS: Feeding donor spleen cells prolonged the survival of skin allografts in mice; combination with CsA led to further prolongation of skin allograft survival.     

The roles of sepsis-induced myeloid derived suppressor cells in mice corneal,skin and combined transplantation

PurposeTo explore the effects of adoptive transferring sepsis induced myeloid-derived suppressor cells (iMDSCs) in mice corneal, skin, and combined corneal–skin survival.MethodsAllogeneic full-thickness corneal transplantation, fully mismatched skin transplantation, and corneal–skin combined transplantation (donor C57BL/6 to recipient Balb/c mice) were performed. Sepsis-induced infectious-MDSCs (iMDSCs), were purified from bone marrow of cecal ligated and punctured (CLP) Balb/c mice. Recipient-derived iMDSCs were adoptively transferred into different recipient groups by retro-orbital injection after surgeries. Corneal and skin grafts were examined and photographed routinely for a period of 45 days. Histopathology was performed to evaluate corneal-graft inflammation. Bone marrow and/or corneal grafts in each group were harvested from executed recipients on postoperative days 15, 25, 35. Corneal cells and bone marrow cells were stained with CD11b-PE and Gr1-FITC, analyzed by FACS.ResultsiMDSCs were able to significantly prolong allograft survival in both corneal and corneal–skin combined transplant groups. A substantial expansion of MDSCs was observed in recipients' bone marrow, particularly in combined groups at an early stage postoperatively, and accordingly the concentration of MDSCs in corneal grafts increased significantly in adoptive transferred groups.ConclusionsSepsis-induced MDSCs may suggest a novel cellular therapeutic approach for preventing various types of allograft rejection.     

Human Skin Xenograft Rejection in CD45 Exon-6 Knockout Mice: The Implication of Involvement of a Direct Pathway

The results of previous studies indicate that only CD4⁺ T cells generated via the indirect pathway play an essential role in causing discordant skin xenograft rejection. The present study was conducted in an attempt to clarify further the roles of effector T cells generated via direct pathways on discordant xenograft rejection using CD45 exon-6 knockout (CD45−/−; C57BL/6 (B6): H-2^b) mice. It has been strongly suggested that CD45 exon-6 knockout mice have profound impairment in T-cell functions via an indirect pathway. When human skin was grafted onto untreated normal C57BL/6 (B6; H-2^b) mice, rejection occurred within 12 days; however, in the CD45 exon-6 knockout mice, the grafts lasted for slightly longer as in fully allogeneic C3H (H-2^k) skin rejection, with a mean survival time ± SD of 19.4 ± 1.5 days and median survival times of 19 days. The difference in survival periods between the human and C3H skin grafts in the CD45 knockout mice was not statistically significant. Both CD4⁺ and CD8⁺ T cells seemed activated in the spleens of these CD45 exon-6 knockout mice 10 days after the human skin grafting. These results suggest that effector T cells generated via a direct pathway can cause discordant skin xenograft rejection, and that CD45 exon-6 knockout mice can generate effector T cells via a direct pathway to reject discordant skin xenografts, similarly to fully allogeneic skin allografts. Received: June 24, 1999 / Accepted: May 30, 2000     

Combined intrathymic and intravenous injection of mesenchymal stem cells can prolong the survival of rat cardiac allograft associated with decrease in miR-155 expression

Background

Mesenchymal stem cells (MSCs) have the potential to improve graft outcomes and promote allograft tolerance. In this study, we examined the effects and mechanism of combined intrathymic (IT) and intravenous (IV) injection of MSCs on the survival of transplanted hearts in a rat allograft model.

Methods

Recipient Sprague-Dawley rats were transplanted with hearts from Wistar rats. Wistar rat MSCs were infused via IT or IV or combined IT and IV (IT/IV) injection at designated intervals. In vitro mixed lymphocyte reaction assays were performed to assess the immunosuppressive capacity of MSCs. Mesenchymal stem cell surface markers and CD4+, CD25+, and Foxp3+ T-cells in the peripheral blood were detected using flow cytometry analysis. The expression of microRNAs and cytokines in graft infiltrating lymphocytes was analyzed by real-time polymerase chain reaction.

Results

The MSCs cultured in vitro had multipotential differentiation capacity. Mixed lymphocyte reaction assays showed that donor-derived MSCs could not stimulate a proliferative response of recipient lymphocytes and could markedly suppress T-cell responses. Survival of the allografts was significantly prolonged by administration of IT/IV injection of MSCs compared with controls, with a mean survival of 32.2 versus 6.5 d, respectively. Compared with the syngeneic groups posttransplant, miR-155 expression was significantly increased in the allogeneic group, and could be restored by injection of MSCs, especially IT/IV injection of MSCs. Moreover, IT/IV injection of MSCs decreased the level of interleukin (IL)-2 and interferon-gamma, but increased the levels of IL-4 and IL-10 in the allogeneic group. More important, IT/IV injection of MSCs was the best way to increase the percentage of CD4+, CD25+, and Foxp3+ T-cell peripheral blood.

Conclusions

Our results indicated that IT/IV injection of MSCs can prolong the survival of rat cardiac allograft, which may be associated with down-regulating miR-155 expression, a shift in the Th1/Th2 balance, and up-regulation of Treg cells expression.     

Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft

Adipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24 days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration.     

Prévention du rejet d'allogreffe intestinale par des anticorps antimolécules d'adhésion dans un modèle murin

Study aimSmall bowel transplantation is still hampered by a high morbidity and mortality linked to the heavy non specific immunosuppression which is required by the transplantation of this lymphoid organ. Adhesion molecules appear to be potential targets for specific immunosuppression. The aim of the study was to investigate the effect of a transitory administration of anti-LFA-1 or anti-α4 monoclonal antibodies (mAb) in the prevention of rejection in a model of fetal small-bowel transplantation in mice.Materials and methodsThe small bowel of C57BL/6 (H-2^b) fetus (16 to 20 days of gestation) was transplanted into adult C3H/He mice (H-2^k) or C57BL/6 recipient mice. Recipients were treated with a short course of either antiLFA-1 mAb alone, either with anti-α4 mAb alone, or with both mAb. Biopsies with histological study of the grafts were performed between post-operative day 5 and 60. A score of development and rejection was assigned to each sample.ResultsNormal intestinal development with no sign of rejection was observed in 24/28 syngenic grafts till postoperative day 45. In the absence of treatment, intense rejection was observed as soon as day 5 and all allogenic grafts were rejected (n=22). In contrast, in anti-LFA-1 mAb treated mice, 18/20 allogenic grafts developed normally with minimal signs of rejection. In anti-α4 treated mice, a transient protective effect on small bowel allograft survival was observed on day 7 but thereafter, all grafts were massively rejected within a few days (n = 18). The combination of both mAb didn't improve the survival of the grafts when compared to anti-LFA-1 mAb treated grafts (n = 10).ConclusionThese results demonstrate that a transitory administration of anti-LFA-1 mAb, but not of anti-α4 mAb, is able to prolong significantly the survival of non vascularized small bowel fetal grafts in mice. Our results are promising for the possible use of the anti-LFA-1 mAb in clinical intestinal transplantation.     

Anti-γ Chain and Anti-IL-2Rβ mAbs in Combination With Donor Splenocyte Transfusion Induce H-Y Skin Graft Acceptance in Murine Model

Background

The common cytokine receptor γ chain signals regulate proliferation, differentiation, and apoptosis of peripheral T cells.

Objective

To investigate whether simultaneous blockade of IL-2Rβ and γ chain signaling in combination with donor splenocyte transfusion (DST) induces transplant tolerance.

Materials and Methods

C57BL/6 (H-2b) mice were randomly divided into 5 groups. In group 1, female mice received only H-Y skin grafts. In group 2, female mice received transfused splenocytes (5 × 10⁶ cells) from syngeneic male mice on day 7 before H-Y skin grafting. In group 3, on days 2 and 4 after DST, female mice received intraperitoneal injections of a mixture of anti-IL-2Rβ monoclonal antibody (mAb) and anti-γ chain mAbs (4G3, 3E12, and TUGm2; 0.5 mg). After DST, group 4 received an intraperitoneal injection of the mixture of anti-γ chain mAbs, and group 5 received intraperitoneal injection of anti-IL-2Rβ mAb (TM-β1). On day 7, H-Y skin grafting was performed.

Results

Group 3 recipients accepted H-Y skin grafts for more than 100 days compared with group 1 (mean survival time [MST], 33.42 days), group 2 (MST, 14.71 days), group 4 (MST, 58.71 days), and group 5 (MST, 17.29 days). Statistical differences (P < .05) were observed between any 2 groups except groups 2 and 5.

Conclusion

Blockade of γ chain signaling rather than IL-2Rβ signaling combined with DST prolongs H-Y skin graft survival. Simultaneous blockade of IL-2Rβ and γ chain signaling may strengthen this effect.     

Rejection of hamster skin xenografts by rats in the absence of anti-hamster antibody formation

Abstract: The hamster to rat xenograft combination is considered to be a “difficult” concordant combination. Although the rat lacks preformed anti-hamster antibodies, there is rapid production of antibodies upon exposure to hamster antigens. When vascularized hamster xenografts are rejected in the rat, anti-hamster antibodies are invariably detected in both the serum and in the rejected tissue. In allogeneic and other concordant xenogeneic (rat to mouse) combinations, rapamycin has been shown to markedly augment the survival of skin grafts in ALS-treated, bone marrow injected mice. We investigated the ability of rapamycin to prolong the survival of skin grafts and block antibody production in the hamster to rat combination. Outbred Golden Syrian hamsters served as skin and marrow donors and Lewis rats were recipients. ALS was administered on days -1, 0, and +2 relative to skin grafting. Rapamycin was administered at 3 mg/kg on alternate days from day +1 through day +13 (seven doses). Donor specific bone marrow was infused IV on day +4 at a dose of either 100 times 10⁶ or 250 times 10⁶ nucleated cells. Antibody titers were determined serially by using a complement dependent cytotoxicity assay. The administration of rapamycin alone (MST 8.5 days) and ALS alone (MST 10 days) prolonged graft survival slightly but significantly compared with untreated controls (MST 7 days). The addition of BM had no additional effect on graft survival beyond that achieved with ALS alone. Rapamycin markedly prolonged skin graft survival when added to ALS (MST 16 days), ALS+BM¹⁰⁰ (MST 19 days), or ALS+BM²⁵⁰ (MST 20.5 days). Rats receiving ALS or ALS+BM produced anti-hamster antibodies in a slightly delayed fashion and at a slightly lower titer when compared to controls. Treatment with rapamycin alone substantially diminished but did not completely eliminate anti-hamster antibody production. Rats receiving rapamycin with ALS or ALS+BM failed to produce anti-hamster antibodies entirely, although they all eventually rejected the hamster skin grafts. Rapamycin, when used in combination with ALS or ALS plus BM is able to prolong skin graft survival and completely abolish antibody production in the hamster to rat combination. The eventual rejection of hamster skin grafts in this circumstance occurs in the absence of anti-hamster antibodies.     

Establishment of a Long-Term Survival Swine Model for the Observation of Transplanted Islets: a Preliminary Step in an Allogeneic Transplant Experiment

BackgroundEvaluation of an experimental and preclinical islet transplantation (IsletTx) model to elucidate associated clinical problems is vital. This study aimed to introduce a simple methodology for producing a swine autologous IsletTx model as a preliminary step in an allogeneic transplant experiment.Methods and MaterialsTwenty-seven pigs were included in the study. Total pancreatectomy (TP) was performed in 8 pigs (TP group), TP with autologous IsletTx in 9 (TP + IsletTx group), and distal pancreatectomy (DP) with autologous IsletTx in 10 (DP + IsletTx group). An open biopsy was performed on all pigs during postoperative day 14 using an infrared imaging (IRI) system. Laboratory data and postoperative survival were analyzed and compared according to the procedures done.ResultsPostoperative survival rate was significantly higher in the pigs with autologous IsletTx than in those without (P = .026). There were no significant differences in survival between the TP + IsletTx and DP + IsletTx groups (P = .746). Significant hyperglycemia was not observed in both groups, but the DP + IsletTx group remained relatively stable throughout the postoperative course. There were no differences in serum creatinine, aspartate aminotransferase, and alanine aminotransferase levels between the 2 groups. By selective liver lobe transplantation and administration of the IRI system, localization of the transplanted islets via open biopsy was achieved.ConclusionsWe successfully developed an autologous IsletTx model and an open biopsy system using a swine model. This study will aid in the development of an allogeneic IsletTx experiment that may improve transplantation outcomes.     

Effects of B cell depletion on T cell allogeneic Immune responses: A strategy to reduce allogeneic sensitization

BackgroundB cell depletion has been employed to treat antibody-mediated organ transplantation rejection, although the effects on cellular immune responses have not been extensively investigated.MethodsA model of B cell depletion used SCID/beige mice reconstituted with BALB/c splenocytes either depleted of B cells (BD) or not (BN). BD and B/N mice received C57BL/6 skin grafts and were sacrificed after 6 weeks (BD-S6 and BN-S6).ResultsRecall proliferative responses of BD-S6 splenocytes to C57BL/6 were significantly reduced compared to BN-S6, and central memory T cells' proportions (CD4⁺CD44⁺CD62L⁺ or CD8⁺CD44⁺CD62L⁺) were significantly decreased in BD-S6 spleens. Recall IFN-γ production by BD-S6 splenocytes was significantly reduced compared to BN-S6 splenocytes (p = 0.0028). Survival times of C57BL/6 heart grafts were significantly longer in SCID/beige mice reconstituted with BD-S6 splenocytes (8.5 ± 1.1 days) than for SCID/beige reconstituted with BN-S6 splenocytes (6.0 ± 1.1 days; p = 0.0006). Under cyclosporine therapy, C57BL/6 heart survival was significantly longer for SCID/beige reconstituted with BD-S6 splenocytes (17.5 ± 6.4 days) than those reconstituted with BN-S6 splenocytes (6.2 ± 1.5 days; p < 0.0001).ConclusionB cell depletion during allogeneic sensitization decreased memory T cells and recalls IFN-γ production and reduced second-set allograft rejection.     

Association between CD34+ and CD3+ T-cells in allogeneic grafts and acute graft-versus-host disease in children undergoing allogeneic hematopoietic stem cell transplantation: A single-center study

BackgroundAcute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We examined the association between the composition of the cell subsets present in allogeneic grafts (allografts) and the occurrence and severity of aGVHD in pediatric patients.MethodsWe retrospectively analyzed 80 consecutive pediatric patients undergoing allo-HSCT at our center.ResultsBoth univariate and multivariate analyses showed that the number of CD34⁺ and CD3⁺ T-cells in allografts were the two highest risk factors associated with II–IV aGVHD. Using receiver operating characteristic analysis, the cutoff levels of the allo-HSCT cell doses were used to divide the recipients into low-dose and high-dose groups. The 100-day cumulative incidence of II-IV aGVHD in the high-dose CD34⁺ and CD3⁺ T-cells group was significantly higher than that of the low-dose group (CD34⁺: 57% vs. 29%, p = 0.009; CD3⁺: 63% vs. 18%, p < 0.001). No other clinical factors or cell subsets correlated with aGVHD incidence.ConclusionsOur analysis indicates that the CD34⁺ and CD3⁺ T-cell numbers in the allografts could be the risk factors for the development of severe aGVHD (level II–IV). Further studies should aim to optimize the critical number of CD34⁺ and CD3⁺ T-cells to reduce the risk of severe aGVHD occurrence in pediatric patients.     

Induction of specific unresponsiveness (tolerance) to skin allografts by intrathymic donor-specific splenocyte injection in antilymphocyte serum-treated mice.

Although chronic immunosuppression has been extremely successful in clinical organ transplantation, it is associated with severe complications such as opportunistic infections, spontaneous neoplasms, drug toxicities, metabolic complications, and the inability to control rejection. We therefore have investigated the ability of allogeneic donor lymphoid cells to produce specific tolerance following intrathymic (IT) injection into allograft recipients. Groups of B6AF1 mice received ALS on days -1 and +2 relative to C3H/He skin grafts on day 0; experimental groups received 1, 5, or 10 x 10(7) syngeneic (B6AF1) or allogeneic (C3H) spleen cells (SPCs) by IT injection on day +7. IT injection of C3H splenocytes significantly prolonged allograft survival at all cell doses tested when compared with ALS controls. The best survival was obtained following IT injection of 5 x 10(7) C3H cells (median survival time [MST] = 132 days; ALS controls = 21.5 days), with 8 of 13 skin grafts surviving longer than 100 days. IT injection of syngeneic splenocytes or third-party DBA/2 splenocytes did not prolong allograft survival beyond that observed in ALS controls. C3H spleen cells injected IT into ALS treated mice on day 0 relative to grafting of C3H skin also produced significant allograft survival (1, 5, or 10 x 10(7) SPCs = MSTs of 75, 47, and 35, respectively) but the results were inferior to those obtained by 5 x 10(7) SPCs IT on day +7. Spleen cells (1 or 5 x 10(7)) injected intraperitoneally or intravenously prolonged allograft survival beyond that seen in ALS controls but were inferior to IT injection at all doses and times studied. Bone marrow, thymocytes, or lymph node cells (5 x 10(7) cells) were substituted for SPCs for IT injection. IT injection of BM, LN or thymocytes all significantly prolonged graft survival over ALS controls. However none of these cell types was as effective as IT splenocytes. Eight B6Af1 recipients of IT splenocytes bearing C3H skin grafts for > 100 days received a second C3H skin graft as well as a simultaneous third-party B10.AKM skin graft. All rejected third-party grafts in normal first-set fashion. Three tolerated both 1st and 2nd C3H grafts without any sign of rejection; 1 rejected the 2nd C3H graft while tolerating the 1st graft; and 4 rejected the 2nd C3H graft in an attenuated fashion but also rejected the 1st graft at the same pace.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative study of different transplantation methods of adipose tissue-derived stem cells in the treatment of erectile dysfunction caused by cavernous nerve injury

We aimed to compare intracavernosal injection (ICI), tail vein injection (IV), and periprostatic injection (PPI) of adipose-derived stem cells (ADSCs) for their ability to improve erectile function in cavernous nerve injury-induced erectile dysfunction (CNIED) rats and to explore the possible mechanism. Eighty-four male SD rats were divided into the sham group (n = 6), BCNI group (bilateral CN crush injury, n = 6), PBS-ICI group (n = 6), PBS-IV group (n = 6), PBS-PPI group (n = 6), ADSC-ICI group (n = 18), ADSC-IV group (n = 18) and ADSC-PPI group (n = 18). ADSCs were labelled with 5-ethynyl-2′-deoxyuridine (EdU), and six rats each in the ADSC-ICI group, ADSC-IV group, and ADSC-PPI group were sacrificed 2, 7, and 28 days after injection. EdU-labelled ADSCs were tracked by immunofluorescence staining. The intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio, neuronal nitric oxide synthase (nNOS)-positive nerve fibres in the dorsal penile nerve and the smooth muscle/collagen ratio in the cavernosum between groups were also evaluated. ADSCs can significantly improve erectile function through ICI or IV. The two are similar in efficacy and superior to PPI. The mechanism may be that after CN injury, ADSCs are recruited to around the MPG and secrete a variety of neurotrophic factors that promote the repair of the CN, thereby improving erectile function.     

Treatment of upper eyelid third-degree burns by dispersed implantation of very small autologous columnar skin grafts: A pilot study of a new method

ObjectiveThis retrospective study compared the effectiveness of dispersed implantation of very small autologous columnar skin (SCS) grafts and full-thickness skin grafts (FTSGs) for treating upper eyelid third-degree burns.MethodsFourteen patients and 26 eyes with granulation tissue formed by third-degree upper eyelid burns were enrolled in the study from August 2017 to June 2020. The experimental group of 6 patients with 11 eyes was treated with SCS grafts. The control group of 8 patients with 15 eyes was treated with FTSGs. The survival rate of the grafts, healing time, SCS diameter, upper eyelid movement distance (ULMD), visual analogue scale (VAS) score for patient satisfaction, and Vancouver Scar Scale (VSS) score were evaluated.ResultsThe difference in the survival rate between the two groups was not statistically significant (P = 0.06). The ULMD and VAS scores in the experimental group were higher than those in the control group (P < 0.05). The healing time was longer in the experimental group than in the control group (P < 0.05). The VSS scores of the donor site and the skin grafting site in the experimental group were lower than those in the control group (P < 0.05).ConclusionUnlike classical skin grafts, SCS implantation surgery can restore the appearance of the upper eyelid, and there is no obvious scar at the donor site. This can be a viable alternative to traditional FTSGs with potential benefits     

Efficacy of Systemic Steroid Use Given One Day After Total Knee Arthroplasty for Pain and Nausea: A Randomized Controlled Study

BackgroundSystemic steroid has been used to control pain and nausea in total knee arthroplasty (TKA), but most studies recommend a single dose administration prior to, or during, surgery. This study aimed to determine the efficacy of administration on 1 day postoperatively.MethodsPatients who were scheduled to undergo TKA were randomly assigned to the following groups: control group, receiving normal saline injection; group 1, receiving 10 mg dexamethasone intravenously (IV) 1 hour before surgery; group 2, receiving 0.1 mg/kg dexamethasone (IV) 24 hours after surgery; or group 3, receiving 0.2 mg/kg dexamethasone (IV) 24 hours after surgery (n = 44-46 per group). Primary outcomes were pain and nausea visual analogue scale (VAS). Secondary outcomes were analgesic administration, rescue antiemetic administration, C-reactive protein, range of motion, and complications.ResultsPostoperative pain and nausea remained high for 48 hours post-TKA. Group 1 had lower pain and nausea VAS scores than did the control group (P < .01) for only 24 hours post-TKA. Groups 2 and 3 had lower pain and nausea VAS scores than did the control group and group 1 (P < .01) 48 hours post-TKA. Analgesic and antiemetic administration were significantly lower in groups 2 and 3 than in the control group during 48 hours after TKA. There were no differences in C-reactive protein level and range of motion, and complications were not detected.ConclusionThe effect of preoperative and postoperative administration of dexamethasone for controlling pain and nausea was observed only for 24 hours. Considering that severe pain and nausea persisted for more than 48 hours after TKA, additional administration of dexamethasone at 1 day postoperatively is suggested.Level of EvidenceLevel I.     

Roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection

An essential role of murine CD4+ T cells in immune reactivity and skin graft rejection in discordant xenogeneic combinations have been reported. Our study was conducted to further clarify the roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection, by using CD4 and CD8 knockout [C57BL/6 Cr Slc (B6; H-2b) background] mice. When human skins were grafted on CD8 knockout mice or B6 mice, both hosts rejected human skin grafts within 12 days after grafting. By contrast, survival of human skin grafts was significantly prolonged in CD4 knockout mice (mean survival times=19.3+/-(SD) 1.6 days; median 19 days). Fully allogeneic C3H/He Slc (H-2k) skin grafts were rejected within 14 days in CD4 knockout mice, suggesting that non-CD4+ T cells in CD4 knockout mice were immunocompetent for allograft rejection. In spleens of these recipient mice, CD8+ T cells seemed to be activated 10 days after human skin grafting. Immunohistological analysis revealed the infiltration of CD8+ T cells at the site of transplanted human skin on CD4 knockout mice. To further examine the role of CD8+ T cells in CD4 knockout mice, human skin grafting was performed on day 0 followed by administration of anti-CD8 monoclonal antibody on days 0, 5, and 14. The administration of anti-CD8 monoclonal antibodies caused the significant prolongation of human skin graft survival. These results indicate the following two conclusions: (1) CD4+ T cells have an essential role in rejecting discordant human skin xenografts rapidly and (2) however, CD8+ T cells also are capable of rejecting discordant human skin xenografts.     

Immunomodulation by intrathymic injection of donor leukocytes in rhesus monkeys.

BACKGROUND: Several studies have demonstrated that intrathymic injection of donor cells into adult rodents can result in long-term allograft survival. The rationale for using the intrathymic route of donor cell administration is that in the thymic environment immature T cells are educated to discriminate between self and non-self antigens. The validity of this approach was tested in non-human primates. METHODS: The effect of the intrathymic injection of allogeneic donor cells was investigated in rhesus monkeys and compared with IV and intracutaneous administration of donor cells. Intrathymic injections were carried out without and with antithymocyte globulin. All animals received subsequently an allogeneic skin graft of the same donor and no immunosuppression post transplantation. RESULTS: Skin graft survival was slightly shorter in animals treated with IC donor cell injections (mean survival time [MST]=8.9+/-0.52) than untreated control animals (MST=10.0+/-0.44), indicating that this route caused sensitisation. Intravenous donor cell injection showed prolongation of graft survival times (MST=11.6+/-1.69). Intrathymic donor cell injection resulted in a graft survival of 9.2+/-1.44 days although addition of antithymocyte globulin slightly prolonged graft survival to 10.3+/-2.84 (not significant). Whereas the cellular responses after intrathymic and intravenous donor cell injections increased, antithymocyte globulin treated animals did not show an increased cellular response. Recipients of intrathymic donor cells showed a significantly decreased humoral anti-donor response as compared to other groups. CONCLUSIONS: Donor cell pretreatment alters the subsequent response to an allogeneic skin graft in monkeys and is dependent on the route of donor cell administration. This is also reflected in the alloantibody response and the in vitro cellular reactivity. Intrathymic administration of donor cells does not lead to prolonged skin graft acceptance.     

Patients’ Characteristics Can Predict Clinical Outcomes Following Hip Arthroscopy by Reflecting the Patterns of Labral Tears: A Retrospective Observational Study

PurposeTo evaluate the relationship between morphological differences in labral tears and clinical features of the hip joint in patients who underwent hip arthroscopy.Materials and MethodsWe retrospectively analyzed data from patients who underwent arthroscopic surgery for the treatment of labral tears. Hip labral tears were morphologically classified as longitudinal peripheral tears (group L), radial fibrillated tears (group FI), radial flaps (group FL), and an unstable labrum (group U). Radiographically, the center–edge angle, acetabular roof obliquity, vertical-center-anterior angle, alpha angle, femoral head-neck offset ratio, and crossover sign were evaluated and compared among the groups. The relationship between labral morphology and these radiographic findings, as well as clinical findings, such as age, gender, preoperative range of hip motion, and the clinical outcomes using modified Harris Hip Score (mHHS) were also examined.ResultsThis study included fifty patients. Groups L and FI were often observed in late middle-aged patients with relatively shallow acetabular coverage. Group FL tears were frequently observed in young males with radiographic features, such as femoroacetabular impingement (FAI), compared to the other groups. Group U comprised mostly young females with relatively shallow acetabular coverage compared to the other groups. For the postoperative mHHS, group FL showed the best score among all groups, with a significant difference between groups FL and FI (p = 0.034).ConclusionsOur study revealed that morphologically, different labral tears were associated with different clinical features and radiological findings. Especially, our study can provide predictive findings for hip arthroscopists that younger males with FAI show better clinical outcomes when compared to middle-aged females with shallow acetabulum, which is indicative of degenerative hip labral tears.Level of evidenceIV case series.     

Tranexamic acid in non-elective primary total hip arthroplasty

PurposeBlood loss during and following elective total hip arthroplasty (THA) can be substantial and may require allogeneic blood transfusions which carries significant risks and morbidity for patients. Intraoperative use of tranexamic acid (TXA) has been proven to reduce the need for allogeneic blood transfusion in elective THA patients. Data regarding TXA efficacy in reducing blood loss in trauma patients undergoing non-elective primary THA is sparse, and its routine use is not well established.MethodsThis is a retrospective analysis of a consecutive cohort of patients who underwent non-elective primary THA in a tertiary medical center between January 1st 2011- December 31st 2019. The cohort was divided into two groups; one received perioperative TXA treatment while the other did not. Blood loss, blood product administration, peri and postoperative complications, readmissions and 1-year mortality were compared between groups.ResultsA total of 419 patients (146 males, 273 females) who underwent THA were included in this study. The "TXA" group consisted 315 patients compared to 104 patients in the "no TXA" group. TXA use reduced postoperative bleeding, as indicated by changes in hemoglobin levels before and after surgery (ΔHb= -2.75 gr/dL vs. ΔHb= -3.34 gr/dL, p<0.001) and by administration of allogeneic blood transfusions (7.0% vs. 16.3%, p = 0.004).ConclusionSimilar to the known effect of TXA in elective THA patients, the use of TXA treatment in patients undergoing non-elective THA led to a significant reduction in postoperative blood loss and in the proportion of patients requiring allogeneic blood transfusions.