Cell Therapies

In the last two decades, the knowledge about stem cells and, specifically, their expansion and differentiation capabilities has grown significantly. These properties (expansion and differentiation) make stem cells unique tools for the treatment of a wide range of diseases, for which traditional therapies have failed or do not exist. Some of the current applications of stem cells are listed in Table 1.2. 

However, to use these cells in clinical protocols, it is necessary to understand the nature and properties of stem cells originating from different tissues, as well as the mechanisms that make them differentiate into mature, functional cells (Mayhall et al., 2004). 

As an alternative to adult stem cells, embryonic stem cells can be used. These are totipotent and can be obtained from the internal blastocyst cell mass. Because of the capacity of these cells to generate any type of functional cell, their manipulation and differentiation have gained in significance. In spite of recent advances (Daley, 2003 Hwang et al., 2004), knowledge on the control of their differentiation and proliferation is still lacking, but will be necessary to make the exploitation of all their therapeutic potential turn into reality. Further discussion on cell therapy can be found in Chapter 20. 

Bone marrow Hematopoietic Cancer Immunodeficiencies Metabolic diseases Hemoglobinopathies Myocardial infarction 

Neuronal embryonic tissue Neuronal Parkinson s disease 

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Cell Saver Cell stnjcture Cell therapy Cellular acetate foam... 

A new field of transfusion medicine, cell therapy, has developed with the better understanding of the function of different cell types ia the body. In cell therapy, various malignancies are treated by transfusion of specific cell types from blood. Therefore, more and more specialized methods for separating blood iato the various components are required. 

A further committee. The Committee for Advance Therapies, is to be established under regulation (EC) No. 1394/2007 to deal with issues raised by emerging drug products based on gene therapy, somatic cell therapy and tissue engineering. 

The Competent Authorities are allowed a maximum of 60 days to review the data, or 90 days in the case of trials involving medicinal products for gene therapy, somatic cell therapy (including xenogeneic cell therapy), and all medicinal products containing genetically modified organisms. Such trials require written authorisation from the Competent Authority as distinct from other types of product where the authorities may just notify the sponsor of the acceptability (no-objection) of the application. If issues are raised, the sponsor may amend the application once, with a consequent extension to the allowed review period. 

Carturan, G., Dal Toso, R., Boninsegna, S. and Dal Monte, R. (2004) Encapsulation of functional cells by sol-gel silica actual progress and perspectives for cell therapy. Journal of Materials Chemistry, 14, 2087-2098. 

Ronaghi M, Erceg S, Moreno-Manzano V, Stojkovic M (2010) Challenges of stem cell therapy for spinal cord injury Human embryonic stem cells, endogenous neural stem cells, or induced pluripotent stem cells Stem Cells 28 93-99... 

Sobajima S et al (2008) Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 8(6) 888-896... 

Gaetani P et al (2008) Adipose-derived stem cell therapy for intervertebral disc regeneration an in vitro reconstructed tissue in alginate capsules. Tissue Eng Part A 14(8) 1415-1423... 

Additional future innovations likely to impact upon pharmaceutical biotechnology include the development of alternative product production systems, alternative methods of delivery and the development of engineered cell-based therapies, particularly stem cell therapy. As mentioned previously, protein-based biotechnology products produced to date are produced in either microbial... 

Cell fusion may underlie some observations of grafted cells 514 COMMON STEM CELL THERAPY CHALLENGES 514 CONCLUSIONS 514... 

Silverman G.J. and Weisman, S., Rituximab therapy and autoimmune disorders prospects for anti-B cell therapy, Arthritis Rheum., 48, 1484, 2003. 

Thompson, J.A. et al., Prolonged continuous intravenous infusion interleukin-2 and lym-phokine-activated killer-cell therapy for metastatic renal cell carcinoma., J. Clin. Oncol., 10, 960, 1992. 

Involvement of several proteolytic enzymes, secretases, is probably crucial for this process but other hypotheses, including, for example, cholinergic transmission or accumulation of metal ions, have also been considered. Future perspectives in this area concern the search for novel pharmaceuticals that cross the blood-brain barrier, without side effects (e.g., the dyskinesias of L-Dopa), or potent and selective inhibitors of improper cleavage of amyloid protein, or even stem cell therapy to restore neuronal cells. 

CeUular Therapies. Since 1984 CBER has reviewed close to 300 somatic cell therapy protocols. Examples of the specific categories include manipulation, selection, mobilization, tumor vaccines and other. 

FDA. (1996). Points to Consider in Human Somatic Cell Therapy and Gene Therapy. 

Kessler, D., Siegel, J., Noguchi, P, Zoon, K., Feidon, K. and Woodcock, J. (1993). Regulation of somatic-cell therapy and gene therapy by the food and Drug Administration. New Engl. J. Med. 329 1169-1173. 

FDA (1996) Addendum to the points to consider in human somatic cell and gene cell therapy, Human Gene Therapy 1 1181-1190. 

Na K, Kim S, Park K, Kim K, Woo DG, Kwon IC, Chung HM, Park KH (2007) Heparin/poly(L-lysine) nanoparticle-coated polymeric microspheres for stem-cell therapy. J Am Chem Soc 129 5788-5789. 

Stem cell therapy— both somatic cell and germ cell... 

Stem Ceii Therapy With stem cell therapy, the aim is to grow body parts to replace defective human organs and nerves. The stem cells are harvested from... 

The potential contribution of stem cells to medical treatment lies in then-capability to differentiate and grow into normal, healthy cells. Using pluripotent stem cells, scientists are devising means to culture them in the laboratories and coax them to grow into various specialized cells. Rather than gene therapy, with stem cells we have the potential of cell therapy to repair our diseased tissues and organs. This will circumvent the lack of donor organs. Stem cells also provide the possibility for healthy cells to cure disabilities such as strokes, Parkinson s disease, and diabetes. 

A drawback for stem cell therapy is the problem of cell rejection due to the host s immune system recognizing the cells as foreign. This rejection issue has to be overcome to ensure stem cell therapy is a viable treatment. Recently, French scientists reported on research progress in stem cell transplants for curing children with sickle cell anemia. A mix of antirejection drugs was used to suppress rejection of the new stem cells. 

Another cell therapy method includes the excision of cells from the body. These cells are then modified and returned to the host body. Provenge, a cancer vaccine using cell therapy, has completed Phase III trial and is being reviewed by the FDA. The technique for this therapy is given in Exhibit 4.17. 

Provenge is a cancer vaccine using cell therapy technique. Dendritic cells are removed from patients. These cells are treated with the prostate-specific antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cases. The activated dendritic cells are returned to the patients and they stimulate the T cells to destroy cancer cells expressing the PAP, thus treating the tumor. 

Stem cells and cell therapy is the use of pluripotent and multipotent cells to generate healthy cells and tissues to replace the faulty ones in disease conditions. The main ethical questions are the source of the cells and the possibility of cloning humans. 

Distinguish the technologies based on gene therapy and cell therapy. Describe the use of vectors for gene delivery. Describe how cell rejection can be overcome in cell therapy. 

Refer to Sections 4.6 and 4.7. The vectors for gene therapy are tabulated in Table 4.5. In cell therapy, antirejection drugs are used to suppress the rejection of transplanted cells. 

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