The promise of treating human genetic and degenerative diseases through the application of pluripotent cell-based tissue engineering and regenerative medicine has come significantly closer to realization since the isolation of human embryonic stem (ES) cells. While the study of ES cells has greatly increased our fundamental understanding of pluripotency, technical and ethical limitations have been seemingly insurmountable impediments to the application of these cells in the clinic. The recent discovery that somatic mammalian cells can be epigenetically reprogrammed to a pluripotent state through the exogenous expression of the transcription factors OCT4, SOX2, KLF4, and c-MYC has yielded a new cell type for potential application in regenerative medicine, the induced pluripotent stem (iPS) cell. Here we discuss how advances in iPS cell technology have led to the generation of patient-specific cell lines that can potentially be used to model human diseases and ultimately act as therapeutic agents.
"Other types of stem cells include somatic stem cells found in differentiated tissues,9 fetal stem cells derived from the fetus,10 and mesenchymal stem cells, a type of multipotent stromal cell.11 It is important to note that one of the most commonly-used assays for demonstrating pluripotency is forming teratomas.12 "
[Show abstract][Hide abstract] ABSTRACT: The procedure of using mature, fully differentiated cells and inducing them toward other cell types while bypassing an intermediate pluripotent state is termed direct reprogramming. Avoiding the pluripotent stage during cellular conversions can be achieved either through ectopic expression of lineage-specific factors (transdifferentiation) or a direct reprogramming process that involves partial reprogramming toward the pluripotent stage. Latest advances in the field seek to alleviate concerns that include teratoma formation or retroviral usage when it comes to delivering reprogramming factors to cells. They also seek to improve efficacy and efficiency of cellular conversion, both in vitro and in vivo. The final products of this reprogramming approach could be then directly implemented in regenerative and personalized medicine.
Stem Cells and Cloning: Advances and Applications 02/2014; 7(1):19-29. DOI:10.2147/SCCAA.S38006
"Current techniques for reprogramming somatic cells into a pluripotent state depend largely on the introduction of reprogramming factors such as OCT3/4, SOX2, KLF4, c-MYC, and/or LIN-28 into the genome (Lengner, 2010; Robinton and Daley, 2012). Retroviral transfer of these genes could culminate in increased incidence of tumor development and/or cellular dysfunction due to both the intrinsic nature of these factors as oncogenes and concomitant genomic modification (Lengner, 2010). In contrast, Sendai virus (SeV) is an ideal vector for reprogramming cells into a pluripotent state without modifying the genome, and thus would be suitable for regenerative medicine (Fusaki et al., 2009; Nishimura et al., 2011; Seki et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Mucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells. We found that human MAIT cells can be reprogrammed into iPSCs using a Sendai virus harboring standard reprogramming factors. Under T cell-permissive conditions, these iPSCs efficiently redifferentiate into MAIT-like lymphocytes expressing the T cell receptor Vα7.2, CD161, and interleukin-18 receptor chain α. Upon incubation with bacteria-fed monocytes, the derived MAIT cells show enhanced production of a broad range of cytokines. Following adoptive transfer into immunocompromised mice, these cells migrate to the bone marrow, liver, spleen, and intestine and protect against Mycobacterium abscessus. Our findings pave the way for further functional analysis of MAIT cells and determination of their therapeutic potential.
"Recently, induced pluripotent stem (iPS) cells, which are obtained by genetically reprogramming adult somatic cells to a pluripotent state, have also been proposed as an alternative cell source for use in regenerative medicine  . However, a number of limitations hamper the clinical applicability of stem cells derived from either adults or developing embryos. "
[Show abstract][Hide abstract] ABSTRACT: The amniotic membrane (AM) and amniotic fluid (AF) have a long history of use in surgical and prenatal diagnostic applications, respectively. In addition, the discovery of cell populations in AM and AF which are widely accessible, nontumorigenic and capable of differentiating into a variety of cell types has stimulated a flurry of research aimed at characterizing the cells and evaluating their potential utility in regenerative medicine. While a major focus of research has been the use of amniotic membrane and fluid in tissue engineering and cell replacement, AM- and AF-derived cells may also have capabilities in protecting and stimulating the repair of injured tissues via paracrine actions, and acting as vectors for biodelivery of exogenous factors to treat injury and diseases. Much progress has been made since the discovery of AM and AF cells with stem cell characteristics nearly a decade ago, but there remain a number of problematic issues stemming from the inherent heterogeneity of these cells as well as inconsistencies in isolation and culturing methods which must be addressed to advance the field towards the development of cell-based therapies. Here, we provide an overview of the recent progress and future perspectives in the use of AM- and AF-derived cells for therapeutic applications.
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