Human cell-based therapies

Considerations in Design of Preclinical Safety Evaluation Programs to Support Human Cell-Based Therapies... 

Finally, lentiviral vectors have been shown to transduce human embryonic stem cells. Therefore, this type of gene-therapy vector might also be used in stem cell-based therapies. 

Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP and Hedrick MH (2001). Multilineage cells from human adipose tissue implications for cell based therapies. Tissue Eng 7 211-228. 

In direct cell implantation, human cells are required but supplies are limited. Production of hepatocytes from pediatric patients has been reported and techniques for preservation are improving. yHfQ characterization of human hepatocytes will aid the development of improved cell-based therapies. The primary safety concern with the use of cell lines, especially implanted cells, is the transmission of toxic factors to the host. 

The first in human trial (FIH) for cell-based therapies is in patients often with no available alternative therapies rather than in normal volunteers. These are also populations where clinical effects are less easy to manifest themselves and where adverse events may be difficult to distinguish from disease-associated events. The surgical procedures and use of immunosuppressants may also contribute to the adverse event profile. Therefore it is even more important to understand the nature and extent of the pathological process underlying the disease symptoms of the patients enrolled in the early clinical trials. 

Zuk PA, et al. Multilineage cells from human adipose tissue implications for cell-based therapies. Tissue Eng 2001 7 211-28. 

Perhaps the application for human stem cells with the most potential is the generation of cells and tissues for the cell-based therapies. The demand for donated organs and tissues far outweighs the supply. Stem cells could possibly be directed toward the production of replacement cells and tissues to treat Parkinson s disease, Alzheimer s disease, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. 

Tsuruga Y, Kiyono T, Matsushita M, Takahashi T, Kasai H, Matsumoto S, Todo S (2008) Establishment of immortalized human hepatocytes by introduction of HPV16 E6/ E7 and hTERT as cell sources for liver cell-based therapy. Cell Transplant 17(9) 1083-1094... 

There is much hope that fundamental research into stem cell biology can eventually be translated into cell-based therapies to treat human disease. Stem cells possess the ability of selfreplication and can be expanded in culture. Stem cells can also be genetically modified and differentiated into aU of the cells comprising tissues that may 1 day be replaced or repaired via tissue-engineering applications. Rapid advances in materials chemistry, photolithography, microfabrication, and microfluidics have provided important new analytic approaches and have led to new insights into the physical chemistry of biological behavior at the subcellular and molecular levels [1]. 

Zuk, P. A., Zhu, M., Mizuno, H., Huang, J.,FutreU, J. W., Katz, A. J.,Benhaim, R, Lorenz, H. R, and Hedrick, M. H., 2001. Multilineage cells from human adipose tissue Implications for cell-based therapies. Tissue Eng7(2) 211-28. 

Ikeda, E., K. Yagi, M. Kojima et al. 2008. Multipotent cells from the human third molar Feasibility of cell-based therapy for liver disease. Differentiation 76 495-505. 

In sum, RNAi clearly has the potential to change the nucleic-based therapies for cancer, infectious diseases, and many other diseases. However, the universality of this approach, the types of genes that can be silenced using these strategies in human cells, remain unknown to date. 

Bai J, Rossi J, Akkina R (2001) Multivalent anti-CCR ribozymes for stem cell-based HIV type 1 gene therapy. AIDS Res Hum Retroviruses 17 385-399 Bai J, Sui J, Zhu RY, TaUarico AS, Gennari F, Zhang D, Marasco WA (2003) Inhibition of Tat-mediated transactivation and HIV-1 replication by human anti-hCychnTl intrabodies. J Biol Chem 278 1433-1442... 

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