Transplantation

About: Transplantation is a research topic. Over the lifetime, 276584 publications have been published within this topic receiving 7961661 citations.

A newly discovered class of human hematopoietic cells with SCID-repopulating activity

Abstract: The detection of primitive hematopoietic cells based on repopulation of immune-deficient mice is a powerful tool to characterize the human stem-cell compartment. Here, we identify a newly discovered human repopulating cell, distinct from previously identified repopulating cells, that initiates multilineage hematopoiesis in NOD/SCID mice. We call such cells CD34neg-SCID repopulating cells, or CD34neg-SRC. CD34neg-SRC are restricted to a Lin-CD34-CD38- population without detectable surface markers for multiple lineages and CD38 or those previously associated with stem cells (HLA-DR, Thy-1 and CD34). In contrast to CD34+ subfractions, Lin-CD34-CD38- cells have low clonogenicity in short-and long-term in vitro assays. The number of CD34neg-SRC increased in short-term suspension cultures in conditions that did not maintain SRC derived from CD34+ populations, providing independent biological evidence of their distinctiveness. The identification of this newly discovered cell demonstrates complexity of the organization of the human stem-cell compartment and has important implications for clinical applications involving stem-cell transplantation.

Bone-graft substitutes: Facts, fictions, and applications

Abstract: It is estimated that more than 500,000 bone-grafting procedures are performed annually in the United States, with approximately half of these procedures related to spine fusion. These numbers easily double on a global basis and indicate a shortage in the availability of musculoskeletal donor tissue traditionally used in these reconstructions (Fig. 1). Fig. 1: United States trends in musculoskeletal tissue donors. Source: United Network for Organ Sharing and the Musculoskeletal Transplant Foundation. This reality has stimulated a proliferation of corporate interest in supplying what is seen as a growing market in bone-substitute materials (Fig. 2). These graft alternatives are subjected to varying degrees of regulatory scrutiny, and thus their true safety and effectiveness in patients may not be known prior to their use by orthopaedic surgeons. It is thus important to gain insight into this emerging class of bone-substitute alternatives. Fig. 2: United States sales of bone graft and bone substitutes. Source: Orthopedic Network News, industry estimates. The biology of bone grafts and their substitutes is appreciated from an understanding of the bone formation processes of osteogenesis, osteoinduction, and osteoconduction. Graft osteogenesis: The cellular elements within a donor graft, which survive transplantation and synthesize new bone at the recipient site. Graft osteoinduction: New bone realized through the active recruitment of host mesenchymal stem cells from the surrounding tissue, which differentiate into bone-forming osteoblasts. This process is facilitated by the presence of growth factors within the graft, principally bone morphogenetic proteins (BMPs). Graft osteoconduction: The facilitation of blood-vessel incursion and new-bone formation into a defined passive trellis structure. All bone graft and bone-graft-substitute materials can be described through these processes. Fresh autogenous cancellous and, to a lesser degree, cortical bone are benchmark graft materials that allograft and bone substitutes attempt to match in in vivo performance. They incorporate all of the above properties, are …

Transduction of Human CD34+ Cells That Mediate Long-Term Engraftment of NOD/SCID Mice by HIV Vectors

Abstract: Efficient gene transfer into human hematopoietic stem cells (HSCs) is an important goal in the study of the hematopoietic system as well as for gene therapy of hematopoietic disorders. A lentiviral vector based on the human immunodeficiency virus (HIV) was able to transduce human CD34+ cells capable of stable, long-term reconstitution of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-efficiency transduction occurred in the absence of cytokine stimulation and resulted in transgene expression in multiple lineages of human hematopoietic cells for up to 22 weeks after transplantation.

Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.

Abstract: Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity. PRDM16 (PR domain containing 16) is a 140 kDa zinc finger protein that robustly induces brown fat determination and differentiation. Recent data suggests that brown fat cells arise in vivo from a Myf5-positive, myoblastic lineage by the action of PRDM16 (ref. 3); however, the molecular mechanisms responsible for this developmental switch is unclear. Here we show that PRDM16 forms a transcriptional complex with the active form of C/EBP-beta (also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells. Forced expression of PRDM16 and C/EBP-beta is sufficient to induce a fully functional brown fat program in naive fibroblastic cells, including skin fibroblasts from mouse and man. Transplantation of fibroblasts expressing these two factors into mice gives rise to an ectopic fat pad with the morphological and biochemical characteristics of brown fat. Like endogenous brown fat, this synthetic brown fat tissue acts as a sink for glucose uptake, as determined by positron emission tomography with fluorodeoxyglucose. These data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes.