Facilitating cells enable engraftment of purified fetal liver stem cells in allogeneic recipients.

It has been reported that while stem cells purified from adult bone marrow engraft in syngeneic recipients, they fail to engraft in allogeneic recipients. We have recently shown that the addition of as few as 30,000 facilitating cells (CD8+/CD3+/CD45R+/Thy 1.2+/TCR-), a unique bone marrow-derived population that does not possess stem cell properties, results in the permanent engraftment of stem cells in a major histocompatibility complex (MHC)-disparate allogeneic host. It has been suggested that fetal hematopoietic tissue may be a source of stem cells with enhanced proliferative and self-renewal properties compared with adult bone marrow. We were interested, therefore, in whether fetal stem cells demonstrated a superior capacity to engraft in allogeneic recipients. In this study, we have examined the engraftment properties of mouse fetal liver cells in syngeneic and allogeneic recipients. Transplantation of unmodified fetal liver cells into allogeneic recipients results in stable multilineage chimerism with donor-specific tolerance, indicating that the pluripotent hematopoietic stem cell is present in fetal liver and is capable of engraftment in allogeneic adult recipients. Similarly, 2000 to 3000 sorted fetal liver stem cells (Sca+/c-kit+/Lin-) successfully reconstituted lethally irradiated syngeneic adults and adults differing only in minor histocompatibility antigens. Two thousand to 10,000 fetal stem cells failed to rescue lethally irradiated allogeneic recipients, but the addition of 30,000 MHC-matched purified facilitating cells to the fetal stem cell inoculum resulted in sustained engraftment with multilineage production. These results, which parallel our earlier work with stem cells derived from adult bone marrow, indicate that the pluripotent fetal stem cell behaves in a fashion similar to that of adult stem cells with regard to allogeneic transplantation.

Management of blunt pancreatic trauma: what's new?

Pancreatic injuries are relatively uncommon but present a major challenge to the surgeon in terms of both diagnosis and management. Pancreatic injuries are associated with significant mortality, primarily due to associated injuries, and pancreas-specific morbidity, especially in cases of delayed diagnosis. Early diagnosis of pancreatic trauma is a key for optimal management, but remains a challenge even with more advanced imaging modalities. For both penetrating and blunt pancreatic injuries, the presence of main pancreatic ductal injury is the major determinant of morbidity and the major factor guiding management decisions. For main pancreatic ductal injury, surgery remains the preferred approach with distal pancreatectomy for most injuries and more conservative surgical management for proximal ductal injuries involving the head of the pancreas. More recently, nonoperative management has been utilized, especially in the pediatric population, with the potential for increased rates of pseudocyst and pancreatic fistulae and the potential for the need for further intervention and increased hospital stay. This review presents recent data focusing on the diagnosis, management, and outcomes of blunt pancreatic injury.

Positive and negative selection of alphabetaTCR+ T cells in thymectomized adult radiation bone marrow chimeras.

BACKGROUND: The mature T-cell repertoire is characterized by the negative selection of potentially autoreactive T cells and the positive selection of T cells restricted to antigen-recognition in the context of self-MHC molecules. It is currently believed that the thymus is critical for these selection events. Although alpha(beta)T cell receptor (TCR)+ T cells have been reported in thymectomized recipients, whether this represents clonal expansion of residual T cells or de novo generation of new T cells in the absence of a thymus has not been definitively evaluated. METHODS: In the current study, development of the T cell repertoire was evaluated in adult radiation bone marrow chimeras prepared after complete surgical thymectomy. RESULTS: CD4+ and CD8+ T cells were present and exhibited donor-specific TCR-Vbeta expression and self-tolerance, indicative of negative selection. Positive selection was confirmed with the demonstration of host MHC restriction and the presence of donor-derived CD8+ T cells after the transplantation of marrow from Class I deficient donors into normal recipients. CONCLUSIONS: These data provide evidence, for the first time, that the development of a functional T-cell repertoire can occur in adult recipients without the thymic microenvironment.

Xenotransplantation.

Transplantation of organs across a species barrier has long been a dream of the transplantation community. Renewed interest in xenotransplantation has emerged due to the short supply of organs available for clinical transplantation. However, transplantation of solid organs across a species barrier has not matched the success of allogeneic combinations, even for closely related species. The rejection response to xenografts is vigorous and not adequately controlled by conventional immunosuppressive agents that control alloreactivity. This may suggest a different mechanism for xenoreactivity, or stronger histocompatibility antigen disparities. This article reviews the current clinical experience with xenografts, mechanisms of xenoreactivity, the induction of tolerance across species disparities, and recent models in which human tissue has been transplanted into other species as an in vivo model of the human immune system.