Showing papers on "Transplantation published in 1994"
TL;DR: Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
Abstract: Background Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. Methods The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. Results Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and s...
5,375 citations
TL;DR: Osteochondral progenitor cells were used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits.
Abstract: Osteochondral progenitor cells were used to repair large, full-thickness defects of the articular cartilage that had been created in the knees of rabbits. Adherent cells from bone marrow, or cells from the periosteum that had been liberated from connective tissue by collagenase digestion, were grown in culture, dispersed in a type-I collagen gel, and transplanted into a large (three-by-six-millimeter), full-thickness (three-millimeter) defect in the weight-bearing surface of the medial femoral condyle. The contralateral knee served as a control: either the defect in that knee was left empty or a cell-free collagen gel was implanted. The periosteal and the bone-marrow-derived cells showed similar patterns of differentiation into articular cartilage and subchondral bone. Specimens of reparative tissue were analyzed with use of a semiquantitative histological grading system and by mechanical testing with employment of a porous indenter to measure the compliance of the tissue at intervals until twenty-four weeks after the operation. There was no apparent difference between the results obtained with the cells from the bone marrow and those from the periosteum. As early as two weeks after transplantation, the autologous osteochondral progenitor cells had uniformly differentiated into chondrocytes throughout the defects. This repair cartilage was subsequently replaced with bone in a proximal-to-distal direction, until, at twenty-four weeks after transplantation, the subchondral bone was completely repaired, without loss of overlying articular cartilage. The mechanical testing data were a useful index of the quality of the long-term repair. Twenty-four weeks after transplantation, the reparative tissue of both the bone-marrow and the periosteal cells was stiffer and less compliant than the tissue derived from the empty defects but less stiff and more compliant than normal cartilage. Clinical Relevance: The current modalities for the repair of defects of the articular cartilage have many disadvantages. The transplantation of progenitor cells that will form cartilage and bone offers a possible alternative to these methods. As demonstrated in this report, autologous, bone-marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro without the loss of their capacity to differentiate into cartilage or bone. Sufficient autologous cells can be generated to initiate the repair of articular cartilage and the reformation of subchondral bone. The repair tissues appear to undergo the same developmental transitions that originally led to the formation of articular tissue in the embryo.(ABSTRACT TRUNCATED AT 400 WORDS)
1,522 citations
TL;DR: It is reported here that stem cells isolated from testes of donor male mice will repopulate sterile testes when injected into seminiferous tubules and may prove useful as a tool for biomedical science and biotechnology.
Abstract: In the adult male, a population of diploid stem-cell spermatogonia continuously undergoes self-renewal and produces progeny cells, which initiate the complex process of cellular differentiation that results in mature spermatozoa. We report here that stem cells isolated from testes of donor male mice will repopulate sterile testes when injected into seminiferous tubules. Donor cell spermatogenesis in recipient testes showed normal morpholigical characteristics and produced mature spermatozoa. This methodology, besides opening new avenues of basic research into spermatogenesis and stem-cell self-renewal, may prove useful as a tool for biomedical science and biotechnology.
1,457 citations
TL;DR: The scaffold induced chondrocyte differentiation with respect to morphology and phenotype and represents a model cell culture substrate that may be useful for a variety of tissue engineering applications.
Abstract: Synthetic polymer scaffolds designed for cell transplantation were reproducibly made on a large scale and studied with respect to biocompatibility, structure and biodegradation rate. Polyglycolic acid (PGA) was extruded and oriented to form 13 μm diameter fibers with desired tenacity. Textile processing techniques were used to produce fibrous scaffolds with a porosity of 97% and sufficient structural integrity to maintain their dimensions when seeded with isolated cartilage cells (chondrocytes) and cultured in vitro at 37°C for 8 weeks. Cartilaginous tissue consisting of glycosaminoglycan and collagen was regenerated in the shape of the original PGA scaffold. The resulting cell-polymer constructs were the largest grown in vitro to date (1 cm diameter × 0.35 cm thick). Construct mass was accurately predicted by accounting for accumulation of tissue components and scaffold degradation. The scaffold induced chondrocyte differentiation with respect to morphology and phenotype and represents a model cell culture substrate that may be useful for a variety of tissue engineering applications.
1,224 citations
TL;DR: It is reported here that testis-derived cells transplanted into the testis of an infertile mouse will colonize seminiferous tubules and initiate spermatogenesis in > 70% of recipients and with recipients that maintained endogenous sperMatogenesis, testis cell transplantation yielded mice in which up to 80% of progeny were sired by donor-derived spermatozoa.
Abstract: Spermatogenesis is a complex, highly organized, very efficient process that is based upon the capacity of stem cell spermatogonia simultaneously to undergo self-renewal and to provide progeny that differentiate into mature spermatozoa. We report here that testis-derived cells transplanted into the testis of an infertile mouse will colonize seminiferous tubules and initiate spermatogenesis in > 70% of recipients. Testis-derived cells from newborn mice were less effective in colonizing recipient testes than cells from 5- to 15- or 21- to 28-day-old mice. Increasing the number of Sertoli cells in the donor cell population did not increase the efficiency of colonization. Unmodified embryonic stem cells were not able to substitute for testis-derived cells in colonizing testes but instead formed tumors in syngeneic as well as nonsyngeneic hosts. Finally, with recipients that maintained endogenous spermatogenesis, testis cell transplantation yielded mice in which up to 80% of progeny were sired by donor-derived spermatozoa. The technique of spermatogonial cell transplantation should provide a means to generate germline modifications in a variety of species following development of spermatogonial culture techniques and should have additional applications in biology, medicine, and agriculture.
1,064 citations
TL;DR: The properties of these cells after transplantation--the stability of resulting hybrid myofibers without immune suppression, the persistence of transgene expression, and the lack of tumorigenicity-- suggest that studies of cell-mediated gene therapy using primary myoblasts can now be broadly applied to mouse models of human muscle and non-muscle diseases.
Abstract: The transplantation of cultured myoblasts into mature skeletal muscle is the basis for a new therapeutic approach to muscle and non-muscle diseases: myoblast-mediated gene therapy. The success of myoblast transplantation for correction of intrinsic muscle defects depends on the fusion of implanted cells with host myofibers. Previous studies in mice have been problematic because they have involved transplantation of established myogenic cell lines or primary muscle cultures. Both of these cell populations have disadvantages: myogenic cell lines are tumorigenic, and primary cultures contain a substantial percentage of non-myogenic cells which will not fuse to host fibers. Furthermore, for both cell populations, immune suppression of the host has been necessary for long-term retention of transplanted cells. To overcome these difficulties, we developed novel culture conditions that permit the purification of mouse myoblasts from primary cultures. Both enriched and clonal populations of primary myoblasts were characterized in assays of cell proliferation and differentiation. Primary myoblasts were dependent on added bFGF for growth and retained the ability to differentiate even after 30 population doublings. The fate of the pure myoblast populations after transplantation was monitored by labeling the cells with the marker enzyme beta-galactosidase (beta-gal) using retroviral mediated gene transfer. Within five days of transplantation into muscle of mature mice, primary myoblasts had fused with host muscle cells to form hybrid myofibers. To examine the immunobiology of primary myoblasts, we compared transplanted cells in syngeneic and allogeneic hosts. Even without immune suppression, the hybrid fibers persisted with continued beta-gal expression up to six months after myoblast transplantation in syngeneic hosts. In allogeneic hosts, the implanted cells were completely eliminated within three weeks. To assess tumorigenicity, primary myoblasts and myoblasts from the C2 myogenic cell line were transplanted into immunodeficient mice. Only C2 myoblasts formed tumors. The ease of isolation, growth, and transfection of primary mouse myoblasts under the conditions described here expand the opportunities to study muscle cell growth and differentiation using myoblasts from normal as well as mutant strains of mice. The properties of these cells after transplantation--the stability of resulting hybrid myofibers without immune suppression, the persistence of transgene expression, and the lack of tumorigenicity--suggest that studies of cell-mediated gene therapy using primary myoblasts can now be broadly applied to mouse models of human muscle and non-muscle diseases.
975 citations
TL;DR: This review emphasizes the fact that the nervous system components governing circadian rhythmicity constitute a specialized subdivision of the vertebrate visual system, and certain transneuronal tracers label only the circadian visual system.
741 citations
TL;DR: Encapsulated human islets were injected intraperitoneally in a diabetic patient with a functioning kidney graft and insulin independence with tight glycaemic control was demonstrated 9 months after the procedure, warranting a trial of a high dose of encapsulated islets in early-onset diabetic patients.
621 citations
TL;DR: Results are consistent with the contention that both myocyte and collagen compartments participate in the development of decompensated eccentric ventricular hypertrophy in the cardiomyopathic heart of ischemic origin.
Abstract: BACKGROUNDIschemic cardiomyopathy is characterized by myocyte loss, reactive cellular hypertrophy, and ventricular scarring. However, the relative contribution of these tissue and cellular processes to late failure remains to be determined.METHODS AND RESULTSTen hearts were obtained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identical number of control hearts were collected at autopsy from patients who died from causes other than cardiovascular disease, and morphometric methodologies were applied to the analysis of the left and right ventricular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed increases of 85%, 47%, and 103%, respectively. Corresponding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricles, was responsible for the difference in th...
589 citations
TL;DR: Results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.
582 citations
TL;DR: The enormous growth potential of adult hepatocytes is demonstrated, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma and their medical usefulness as donor cells for transplantation.
Abstract: Adult liver has the unusual ability to fully regenerate after injury. Although regeneration is accomplished by the division of mature hepatocytes, the replicative potential of these cells is unknown. Here, the replicative capacity of adult liver cells and their medical usefulness as donor cells for transplantation were investigated by transfer of adult mouse liver cells into transgenic mice that display an endogenous defect in hepatic growth potential and function. The transplanted liver cell populations replaced up to 80 percent of the diseased recipient liver. These findings demonstrate the enormous growth potential of adult hepatocytes, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma.
TL;DR: Rates of primary nonfunction and initial poor function might be reduced by avoidance of combinations of risk factors, particularly warm ischemia time.
TL;DR: It is concluded that porcine pancreatic endocrine tissue can survive in the human body and be transplanted to insulin-dependent diabetic kidney-transplant patients.
TL;DR: UDCA was extraordinarily safe and well tolerated, and its use was associated with delayed progression of the disease as defined in this study, however, the lack of effects on symptoms, histology, and the need for liver transplantation or survival indicate that further evaluation is necessary.
TL;DR: Progress has been made on improving the result of biliary reconstruction after OLTx, and if significant additional improvement in patient and graft survival are to be obtained, the technical performance of OLTx must continue to improve.
Abstract: Objective This study analyzed the incidence and timing of biliary tract complications after orthotopic liver transplantation (OLTx) in 1792 consecutive patients. These results were then compared with those of previously reported series. Finally, recommendations were made on appropriate management strategies. Summary background data Technical complications after OLTx have a significant impact on patient and graft survival. One of the principal technical advances has been the standardization of techniques for biliary reconstruction. Nonetheless, biliary complications still occur. A 1983 report from the University of Pittsburgh reported biliary complications in 19% of all transplants, and an update in 1987 reported biliary complications in 13.2% of transplants. Methods The medical records of all patients who underwent liver transplantation and were hospitalized between January 1, 1988 and July 31, 1991 were reviewed. The case material consisted of the medical records of 217 patients treated for 245 biliary complications. Results Primary biliary continuity was established by either choledochocholedochostomy over a T-tube (C-C, n = 129) or a Roux-en-Y choledochojejunostomy with an internal stent (C-RY, n = 85). The overall incidence for biliary complication in this large series was 11.5%. Strictures (n = 93) and bile leak (n = 58) were the most common complications (69.6%). Most biliary complications (n = 143, 66%) occurred within the first 3 months after surgery. In general, leaks occurred early, and strictures developed later. Bile leaks were equally frequent in both C-C and C-RY (27.1% and 25.9%, respectively); strictures were more common after a C-RY type of reconstruction (36.4% and 52.9%, respectively). Twenty-one patients died, an incidence of 9.6%. Fifteen of the 21 biliary-related deaths were among patients treated for rejection before the recognition of biliary tract pathologic findings. Conclusions Progress has been made on improving the results of biliary reconstruction after OLTx. Nonetheless, patients continue to experience biliary complications after OLTx, and these complications cause considerable loss of grafts and life. If significant additional improvement in patient and graft survival are to be obtained, the technical performance of OLTx must continue to improve.
TL;DR: Risk of graft failure varies substantially, even within a high-risk population, and the number of risk factors present should be considered by the patient and surgeon when contemplating transplantation and planning follow-up.
TL;DR: HRV at 0.1 Hz depends on factors in addition to cardiac sympathetic nerve firing rates, including multiple neural reflexes, cardiac adrenergic receptor sensitivity, postsynaptic signal transduction, and electrochemical coupling, and is not directly related to cardiac norepinephrine spillover, which is a more direct measure of the sympathetic nerve fired rate.
Abstract: BACKGROUNDAlthough heart rate variability (HRV) at 0.1 Hz has been proposed as a noninvasive clinical measure of cardiac sympathetic nerve firing, this premise has not been sufficiently validated by comparison with techniques such as microneurography and the measurement of norepinephrine spillover from the heart that more directly reflect presynaptic sympathetic activity.METHODS AND RESULTSWe compared the three techniques under conditions of effective cardiac sympathetic denervation, pure autonomic failure (n = 4), dopamine beta-hydroxylase deficiency (n = 1), and after cardiac transplantation (n = 9) as well as in the context of sympathetic nervous activation in cardiac failure (n = 15) and with aging (n = 10). Age-matched comparisons were made in each case with healthy individuals drawn from a pool of 52 volunteers. In pure autonomic failure and early after transplantation, cardiac norepinephrine spillover was negligible, and HRV was low. Late after transplantation, however, cardiac norepinephrine spill...
TL;DR: CD34+ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy.
Abstract: PURPOSETo evaluate the capacity of enriched CD34-positive (CD34+) progenitor cells to reconstitute hematopoiesis in poor-prognosis breast cancer patients following administration of a high-dose alkylating agent chemotherapy regimen.PATIENTS AND METHODSForty-four breast cancer patients received high-dose chemotherapy followed by autologous bone marrow support (ABMS) with CD34+ hematopoietic progenitor cells in five sequentially treated cohorts. Following infusion of CD34+ marrow, cohort no. 1 received no growth factor, cohort no. 2 received granulocyte colony-stimulating factor (G-CSF), and cohort no. 3 received granulocyte-macrophage colony-stimulating factor (GM-CSF). Cohort no. 4 received the CD34+ fractions of both marrow and peripheral-blood progenitor cells (PBPCs) plus G-CSF. Cohort no. 5 received only the CD34+ PBPCs plus G-CSF. Immunohistochemical staining for breast cancer was performed on all hematopoietic cell products before and after the positive selection procedure, to assess quantitatively ...
TL;DR: The regeneration of injured dorsal root axons into the adult spinal cord was possible after ensheathing glia transplantation, and the use of ens heathing cells as stimulators of axonal growth might be generalized to other central nervous system injuries.
TL;DR: The marker-gene technique described should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.
TL;DR: Residual viable myocardium after myocardial infarction may act as an unstable substrate for further events unless it is revascularized, and age and left ventricular dysfunction remained the strongest predictors of cardiac death in these patients with a spectrum of left Ventricular dysfunction.
Abstract: BACKGROUNDThe uptake of F-18 deoxyglucose into dysfunction segments after myocardial infarction identifies metabolically active (FDG+) or inactive (FDG-) myocardium Although patients with FDG+ segments have been found to be at risk for adverse events, the prognostic significance of viable myocardium in relation to other influences on postinfarction prognosis, including revascularization, remain ill defined The purpose of this study was to investigate the relative prognostic significance of FDG+ tissue and to establish whether myocardial revascularization in patients with viable tissue attenuates the risk of adverse outcomeMETHODS AND RESULTSOne hundred thirty-seven patients with left ventricular dysfunction and resting perfusion defects after myocardial infarction underwent positron emission tomography with both dipyridamole stress Rb-82 perfusion imaging and FDG imaging After the exclusion of 4 patients proceeding to transplantation, 2 with uninterpretable scans and 2 lost to follow-up, 129 patients
TL;DR: This is the first report of reduced-size liver transplant in a patient with CAPV, and the authors' experience and a review of the literature indicate that the CAPV can be classified into one of two groups of portasystemic anomalies.
TL;DR: The authors still have much to learn about the function and clinical potential of this and other potentially redundant costimulatory pathways and therefore they suspect that this story will become considerably more complex over the next few years.
TL;DR: Rh-SOD has the potential to mitigate free radical-mediated reperfusion injury-induced acute endothelial cell damage that potentially may contribute to the process of chronic obliterative rejection arteriosclerosis and in accordance with the "response-to-injury hypothesis" in the pathogenesis of general atherosclerosis.
Abstract: In a prospective randomized double-blind placebo-controlled trial, the effect of rh-SOD, given in a dose of 200 mg intravenously during surgery to cyclosporine-treated recipients of cadaveric renal allografts, on both acute and chronic rejection events as well as patient and graft survival was investigated by analyzing the patients' charts retrospectively. The results obtained show that rh-SOD exerts a beneficial effect on acute rejection events as indicated by a significant reduction of (1) first acute rejection episodes from 33.3% in controls to 18.5%, as well as (2) early irreversible acute rejection from 12.5% in controls to 3.7%. With regard to long-term results, there was a significant improvement of the actual 4-year graft survival rate in rh-SOD-treated patients to 74% (with a projected half-life of 15 years) compared with 52% in controls (with an extrapolated half-life of 5 years). The beneficial effect of rh-SOD observed in this trial is not fully understood, although one can assume that the effect is related to its antioxidant action on ischemia/reperfusion injury of the renal allograft, thereby potentially reducing the immunogenicity of the graft. In addition and in accordance with the "response-to-injury hypothesis" in the pathogenesis of general atherosclerosis, rh-SOD has the potential to mitigate free radical-mediated reperfusion injury-induced acute endothelial cell damage that potentially may contribute to the process of chronic obliterative rejection arteriosclerosis.
TL;DR: Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation, and studies of the adsorbed proteins should provide information about the mechanism of this disease.
Abstract: Background Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome. Methods Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured. Results The protein-adsorption treatment consistently decrea...
TL;DR: Delicate tissue handling and the small total amount of fat transplanted by careful distribution in the recipient tissues are probably the factors responsible for the long-lasting improvement in these patients.
Abstract: Nine cases of idiopathic constitutional subcutaneous fat atrophy in the cheek area during the years 1988-1992 were treated by the autologous transplantation of fat for purely aesthetic reasons. The fat graft suspension was obtained by the low-power aspiration technique with the use of a vacuum pump. The contour defects were initially overcorrected by approximately 50 percent more volume than required. The patients were followed up for 1.5 to 4.5 (mean, 3.5) years. Contrary to the experience of others, only the partial resorption of the transplanted fat occurred. This result was verified by six biopsy specimens obtained in the time range of 7 to 36 months after transplantation. The additional injections of fat were not necessary. Delicate tissue handling and the small total amount of fat transplanted by careful distribution in the recipient tissues are probably the factors responsible for the long-lasting improvement in these patients. As an experiment, suction of fat under -0.5 atm and -0.95 atm was performed in five patients undergoing abdominal liposuction. Aspiration under maximum negative pressure caused partial breakage and vaporization of the fatty tissue. The diameter of the fat cells in the remaining beads of fat was in all five cases mechanically distended and thus was larger than in the lipocytes extracted at -0.5 atm.
TL;DR: PCR offers a rapid, sensitive diagnostic method for myocardial viral infection while enterovirus is an important etiological agent, adenovirus was more prevalent in this series and should be evaluated when etiology is sought.
Abstract: BACKGROUNDThe diagnosis of viral myocarditis remains difficult and generally depends on clinical and histological criteria. Viral cultures and serology are often unrewarding, with low yields. The purpose of this study was to analyze the usefulness of polymerase chain reaction (PCR) in the rapid diagnosis of acute myocarditis in children.METHODS AND RESULTSPCR was used to analyze 38 myocardial tissue samples from 34 patients with suspected acute viral myocarditis and 17 control patients with congenital heart disease (14) or hypertrophic cardiomyopathy (3). Myocardial samples were obtained at the time of right ventricular biopsy (13 samples), from explanted hearts (18 samples) at transplantation, and from cardiac autopsy specimens (24 samples) and were evaluated for the presence of enterovirus, cytomegalovirus (CMV), adenovirus, and herpes simplex virus (HSV) using PCR primers designed to consensus and unique sequences of these viral genomes. Blood also was obtained at the time of biopsy (11) or transplant ...
TL;DR: Neither the eligible group nor the curative group showed significant differences between the two trial transfusions in survival, disease-free survival, cancer recurrence rates, or overall infection rates after an average follow-up of 36 months, and the relation is not due to promotion of cancer.
TL;DR: A quantitative difference in circulating EBV viral load and EBNA antibody levels is evident between transplant recipients with and without PTLD and may be useful as a noninvasive prognostic marker with which to monitor and/or predict the development of PTLD.
TL;DR: It is shown that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients and demonstrated donor- specific transplantation tolerance when tested with donor-specific and third-party skin grafts.
Abstract: The rejection of the transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD28. CTLA4-Ig is a fusion protein that has previously been shown to block the CD28-mediated costimulatory signal and inhibit immune responses in vitro and in vivo. In this report we show that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients. In addition, these recipients demonstrated donor-specific transplantation tolerance when tested with donor-specific (BALB/c) and third-party (C57BL/10) skin grafts. These results demonstrate that CTLA4-Ig can induce transplantation tolerance in the adult murine cardiac allograft model.