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Biomedical subjects

G Mai

Publications and source records attributed to G Mai.

23 records · Page 2Linked to original sources
PubMedDate not supplied

Phylogenetic disparity influences the predominance of direct over indirect pathway of antigen presentation in islet xenotransplantation.

BACKGROUND: Cellular immunity plays a major role in rejection of xenografted islets. Depending on the phylogenetical disparity, direct or indirect antigen presentation is predominant. The aim of this study was to analyze in vitro the predominance of direct or indirect presentation, and in vivo the effect of macrophage depletion on concordant and discordant islet xenograft survival. MATERIALS AND METHODS: In vitro, we performed mouse antirat and mouse antihuman mixed lymphocyte reactions (MLR) after depletion of responder or stimulator antigen-presenting cells. In vivo, streptozotocin-induced diabetic C57BL/6 mice were treated by gadolinium chloride to deplete macrophages and rat or human islets were transplanted under the kidney capsule. Islet function was followed by glycemia and xenografts were analyzed at regular intervals for histology. RESULTS: Mouse antirat MLR showed a predominant direct antigen presentation pathway, whereas in mouse antihuman MLR, direct and indirect pathways were similarly involved. Survival of rat islets was not modified by GdCl therapy. In contrast, survival of human islets was significantly prolonged in GdCl-treated mice. Macrophage infiltration was decreased in concordant and discordant GdCl-treated xenografts at day 4, compared to controls. At day 15, macrophage infiltration was similar in all groups. DISCUSSION: Our results indicate that direct antigen presentation is dominant in rejection of concordant islet xenografts and cannot be influenced by host macrophage depletion. Both direct and indirect antigen presentation are involved in rejection of discordant xenogeneic islets. Macrophage depletion or inhibition should be considered as therapeutic tool for discordant islet xenotransplantation.

Animals↗
PubMedDate not supplied

Role of CD40-CD154 pathway in the rejection of concordant and discordant xenogeneic islets.

BACKGROUND: Costimulatory blockade has been shown to allow long-term survival of xenogeneic islets. The aim of the present study was to evaluate the role of recipient CD40 and CD154 in the rejection process of concordant and discordant islet xenotransplantation (Tx). METHODS: Diabetic C57BL/6 mice, CD40- or CD154 knockout (KO) mice were transplanted with either concordant rat or discordant human islets. EXPERIMENTAL DESIGN: group 1, control (ie, C57BL/6 mice received islet Tx without therapy); group 2, C57BL/6 mice received islet Tx with anti-CD154 monoclonal Ab (mAb) therapy; group 3, CD40 KO mice; and group 4, CD154 KO mice were used as recipients without therapy. Mouse anti-rat mixed lymphocyte reactions (MLR) were performed using mouse splenocytes obtained from animals transplanted with rat islets in groups 1 to 4. RESULTS: In group 2, short-term anti-CD154 mAb therapy significantly prolonged rat-to-mouse and human-to-mouse xenograft survival, compared to controls. In CD40-KO and CD154-KO recipients, survival of concordant or discordant islets was not prolonged significantly compared to control groups. Mouse anti-donor rat cellular responses were reduced approximately 50% in group 2 but remained unmodified in groups 3 and 4, when compared to group 1. CONCLUSIONS: Improved graft survival and reduced MLR responses against donor cells in vitro among the anti-CD154 mAb-treated mice could be explained by specific targeting of activated T cells with subsequent inactivation by anergy and/or elimination by apoptosis, or complement- or cellular-mediated mechanisms. Rejection of xenografts and strong MLR responses against donor cells in vitro in CD40 or CD154 KO animals is possible through efficient activation of alternate pathways of costimulation.

Animals↗
PubMedDate not supplied

Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes.

BACKGROUND: The aim of this study was to evaluate the in vitro and in vivo function of hepatocytes after immortalization, cryopreservation, encapsulation, and xenotransplantation into mice with fulminant liver failure (FLF). METHODS: Rat and human hepatocytes were isolated by collagenase digestion. Human hepatocytes were immortalized using lentiviral vectors. Rat and immortalized human hepatocytes (IHH) were encapsulated in 400 microm of alginate-poly-L-lysine (PLL; Sigma, Buchs, Switzerland)-alginate membranes and cryopreserved using a computerized device. In vitro, encapsulated hepatocytes (cryopreserved or noncryopreserved) were cultured; albumin secretion was measured by enzyme-linked immunosorbent assay. Microencapsulated (cryopreserved or noncryopreserved) hepatocytes were transplanted intraperitoneally to mice with FLF: group 1 (n = 10) transplantation of empty capsules; group 2 (n = 12) transplantation of free primary rat hepatocytes; group 3 (n = 12) transplantation of cryopreserved encapsulated rat hepatocytes; group 4 (n = 10) transplantation of encapsulated rat hepatocytes; group 5 (n = 9) transplantation of cryopreserved encapsulated IHH; group 6 (n = 10) transplantation of encapsulated IHH. RESULTS: Compared with free primary hepatocytes, cryopreserved or noncryopreserved encapsulated rodent hepatocytes showed similar levels of continuous in vitro albumin secretion over 1 week. Cryopreserved or noncryopreserved encapsulated IHH showed minimal albumin secretion compared with free primary human hepatocytes. Fulminant liver failure, produced by a combination of acetaminophen and 30% hepatectomy, resulted in a 20% to 30% host survival. In groups 1 and 2, survival was unmodified, compared with untreated mice. For groups 3 and 4, transplantation of cryopreserved or noncryopreserved encapsulated rat hepatocytes significantly increased survival rates to 66% and 80%, respectively (P < .01). For groups 5 and 6, transplantation of cryopreserved or noncryopreserved encapsulated IHH improved host survival to 50% and 55%, respectively (P < .05). CONCLUSIONS: Primary rodent hepatocytes maintained synthetic functions after encapsulation and cryopreservation. Immortalized human hepatocytes showed minimal albumin secretion in the absence of encapsulation and cryopreservation, suggesting that hepatocytes lose some specific functions after immortalization. After induction of FLF in mice, intraperitoneal transplantation of encapsulated (primary or immortalized, cryopreserved or noncryopreserved) xenogeneic hepatocytes significantly improved survival. These results indicate that naive and genetically modified hepatocytes can be successfully encapsulated, stored by cryopreservation, and transplanted into xenogeneic recipients with FLF to sustain liver metabolic functions.

Animals↗
PubMedDate not supplied

[Malformations of the human tail bud or: caudal agenesis syndrome. A review].

This study presents radiological and clinical findings in 70 patients with aplasia of caudal spinal segments and associated anomalies of the lower extremities and the inner organs. From a functional point of view 5 different types can be classified--unilateral hemi-aplasia, bilateral aplasia with or without sacral plateau, complex malformations of the caudal spine and medial spinal aplasia. Foot deformities and anomalies of the inner organs are common findings regardless to the extent of spinal aplasia, whereas popliteal webbing is only seen in cases with involvement of the lumbar spine. The lack of osseous junction between the spine and the pelvis leeds to a lumbopelvic kyphosis. Additionally the iliac wings are rotated in the frontal plane with the result of a narrow pelvic outlet and a change in the geometry of the hip joints. Embryologically all types of caudal spinal aplasia can be referred to a damage of the human tail bud. However, the term "Syndrome of Caudal Regression" is misleading; with respect to the presented results it is proposed to call this type of spinal malformation "Syndrome of Caudal Aplasia".

Abnormalities, Multiple↗