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At least 919 records · Page 51Linked to original sources
PubMed1991

New developments in bone marrow transplantation.

A better understanding of the immunobiology after transplantation and of the available recombinant cytokines that enhance hematopoietic reconstitution following autologous and allogeneic bone marrow transplantation is likely to result in safer application of bone marrow transplantation. Residual tumor cells escaping chemotherapy or chemoradiotherapy given in the course of autologous and allogeneic bone marrow transplantation are still a barrier to complete eradication of malignancy. Recent experiments in animal models of human disease suggest that minimal residual disease can be controlled by an innovative therapy consisting of the administration of cytokines such as recombinant human interleukin-2 and interferon-alpha. Moreover, graft versus leukemia-like effects are induced in conjunction with autologous and allogeneic bone marrow transplantation by administration of allogeneic immunocompetent lymphocytes and recombinant interleukin-2 following bone marrow transplantation and especially by combined administration of allogeneic lymphocytes and recombinant interleukin-2. Similar approaches are currently being investigated in humans with encouraging preliminary results. Overall, our data suggest that eradication of the last tumor cell is neither feasible nor necessary for achieving operational cure. Control of minimal residual disease by activation of anticancer effector cells today seems closer than ever and we are optimistic that further advances in immunotherapy will be applicable to clinical practice in the near future.

Animals↗
PubMed2007

Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation.

Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor T cells secrete IFN-gamma, which in turn stimulates the programmed cell death of thymic epithelial cells (TECs). Because TECs themselves are competent and sufficient to prime naive allospecific T cells and to elicit their effector function, the elimination of host-type professional antigen-presenting cells (APCs) does not prevent donor T-cell activation and TEC apoptosis, thus precluding normal thymopoiesis in transplant recipients. Hence, strategies that protect TECs may be necessary to improve immune reconstitution following allogeneic bone marrow transplantation.

Acute Disease↗
PubMed1986

Human platelet-derived transforming growth factor-beta stimulates parameters of bone growth in fetal rat calvariae.

Human platelet-derived transforming growth factor type beta (TGF beta) is mitogenic for fetal rat calvariae in serum-free organ culture. It enhances DNA synthesis in short (24-h) and long (48- to 96-h) term cultures, but produces no significant stimulatory effects on bone collagen synthesis or alkaline phosphatase activity (two parameters of differentiated osteoblastic cell-type function) when present continuously in culture. Transitory treatment with TGF beta, however, induces a subsequent stimulation of collagen and noncollagen protein synthesis that depends on prior cell replication, suggesting an increase in the number of newly differentiated bone cells. In addition, TGF beta increases prostaglandin release, but this effect is probably unrelated to its mitogenic function. TGF beta activity is also found in culture medium conditioned by fetal rat calvariae, and the bone-derived factor produces effects similar to those of the human platelet factor. This polypeptide, therefore, may have an important function in early stages of bone development as well as bone repair after trauma-induced platelet degranulation.

Animals↗
PubMed1999

The development of bone changes induced in rats by recombinant human granulocyte colony-stimulating factor is suppressed by bisphosphonate.

We have previously demonstrated that high doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) induce bone changes characterized by osteoclastic bone resorption and osteogenesis due to intramembranous ossification in rats. In this communication we examined the effects of a pretreatment with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), which is a powerful inhibitor of osteoclastic bone resorption, on bone changes induced by rhG-CSF in order to investigate the relation between osteoclastic bone resorption and osteogenesis. AHPrBP (5 mg/kg/day) was subcutaneously given to 6-week-old rats for 2 days. From the following day of the final injection of AHPrBP, rats received a subcutaneous injection of rhG-CSF (1,000 micrograms/kg/day) for 14 days, and the femur and tibia were evaluated histopathologically. By the analysis of peripheral blood leukocyte counts, spleen weights and bone marrow findings, the pretreatment with AHPrBP had no effect on the activation of hematopoiesis related to the major pharmacological activity of rhG-CSF. In the rats treated with rhG-CSF alone, accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification were observed in the trabeculae of metaphyseal spongiosa. The accelerated osteoclastic bone resorption induced by rhG-CSF was suppressed by the pharmacological activity of AHPrBP. Furthermore, the osteogenesis induced by rhG-CSF was also suppressed by AHPrBP. These results suggest that the osteogenesis induced by rhG-CSF is a sequential reaction of accelerated osteoclastic bone resorption, and moreover that the main action of rhG-CSF on bone is an acceleration of osteoclastic bone resorption.

Animals↗
PubMed1995

Microgravity generated by space flight has little effect on the growth and development of chick embryonic bone.

Seven days' space flight of fertilized chicken eggs pre- incubated for 7 and 10 days on earth caused no differences in the morphology of osteoblasts, osteoclasts, and osteocytes of humerus and tibia from those of control embryos. Bone-resorbing and -forming activities of the femur were not different between control and flight groups. As a consequence, calcium and phosphorus contents of the femora between control and flight groups were not changed. Alkaline phosphatase activity of 3 different regions (resting cartilage, growth cartilage, and cortical bone) of tibia showed no significant difference between control and flight groups. No significant difference of gene expressions of hepatocyte growth factor and receptors of fibroblast growth factor was observed in perichondrium, trabecula, and skeletal muscles and tendons of hind limbs between control and flight groups. Unlike the results of previous space flight experiments in which young growing mammals were used, these morphological and biochemical results indicate that microgravity has little effect on bone metabolism of the chick embryo.

Actins↗