Tissue transplantation therapy

Under the revised system, CBER will continue to review blood products and vaccines. These product areas are CBER s strengths and the basis for creation of the biologies division. CBERwill also be responsible for evaluating gene therapy and tissue transplantation products as the development of these novel entities comes to fruition. 

Azathioprine is administered to patients who do not respond to calcineurin inhibitors, sirolimus and glucocorticoids. Daily doses of 3-10 mg/kg of azathioprine are administered 1 or 2 days before renal transplantation or on the day of surgery for prophylactic therapy. Mycophenolate mofetil is increasingly used in place of azathioprine for tissue transplantation since it is less myelotoxic and causes few opportunistic infections. 

Basiliximab is used for the prophylaxis of acute rejection for patients undergoing kidney transplantation where it is employed in combination with other standard immunosuppressive therapy regimens. After tissue transplantation, its addition to the standard immunosuppressive regimen results in inhibiting tissue rejection up to approximately 30%. Both daclizumab and basiliximab have similar effects on the expression of IL-2a and -(3 chains. 

The loss of bone mineral after organ and tissue transplant associated with immunosuppressive therapy follows a delayed time course. The long-term effects of immunosuppressive therapy on bone density have been determined in 25 cardiac transplant patients (SEDA-20, 375) (219). As expected, there was bone loss in the spine during the first year, but this was not maintained during the second and third years after transplantation, despite continuing maintenance immunosuppression with prednisolone. Only four patients, all of whom were hypogonadal, continued to lose bone. 

The potential benefits of alleviating dopamine deficiency in the brains of Parkinson s patients by tissue implantation have been widely discussed from both clinical and ethical perspectives. Conventional dopamine replacement therapy suffers from well known and serious limitations. The most recent data indicate that fetal-tissue transplants into patients with idiopathic or MPTP-induced Parkinson s disease are clinically encouraging and may be highly beneficial for at least some patients (6,7). 

Organ transplants and cellular and free tissue transplants are subject to cellular rejection. In allotransplantation, cellular rejection is controlled by conventional immunosuppressive therapy, but there is concern that, for several reasons, cellular rejection may be especially severe in xenotransplants. First, the great variety of antigenic proteins in a xenograft may lead to recruitment of a diverse set of xenoreactive T-cells. Second, the... 

It has been proposed that embryonic stem cells should be used for tissue-replacement therapies by inducing them to differentiate into particular cell types, i.e., heart muscle cells or neurons. At present, the factors required to differentiate embryonic cells into specific cell lineages are only partly known. In addition, the use of human embryonic stem cells is burdened with ethical and legal concerns. Fortunately, there is increasing evidence that adult stem cells may be more abundant than expected, and thus may present an alternative to human embryonic stem cells in cell therapies. Such cells had been previously known in the hemapoietic system and are used in bone-marrow transplantation for the treatment of leukemias. Only recently, they have been identified in many other organs as well, including brain [11]. More im-... 

Biotechnology cell and molecular biology transplantation genetic engineering cell and tissue transplantation cloning ceU-based therapies regenerative medicine. 

Principal therapies for bone defects and injuries include bone-tissue transplantation, artificial prosthesis implantation and tissue-engineering treatments. Autologous transplantation of cells and tissue is the gold standard (Healy and Guldberg, 2007). The scarcity of autologous tissue, however, limits its further application (Healy and Guldberg, 2007). Therefore, much effort has been put into the development of other approaches. 

Regardless of the cell type used, many barriers must be overcome for the field of CSC transplantation therapy to move forward and become clinically applicable. For example, it is not yet known how to keep a majority of the transplanted cells alive for more than a few days (Zhang et al., 2010), and therefore, for any cell-based therapy to work effectively, a prosurvival strategy should be developed, since in the harsh hypoxic environment of the infarcted heart one expects the level of cell death and fibrosis to be significant. In addition, the impact of parameters such as the optimal number and timing of stem cell transplantation post-MI are currently unknown. The success of cell transplantation for cardiac tissue... 

HF due to ischemic heart disease is one of the leading causes of worldwide mortality. While current clinical therapies can improve hemodynamics in HF, currently there is no viable option for replacing damaged cardiac muscle cells. Stem cell transplantation therapy offers tremendous potential to regenerate the myocardium and improve overall quality of life. However, there are several critical challenges with stem cell transplantation such as poor cell retention at the site of transplantation, survival, and eventual functional integration into the diseased tissue. Various natural and synthetic biomaterials have been explored to enhance cell retention and survival in the ischemic myocardium, and ultimately... 

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