Reprogrammed Pluripotent Stem Cells from Somatic Cells

Abstract

Pluripotent stem cells, such as embryonic stem (ES) cells, can differentiate into all cell types. So, these cells can be a biological resource for regenerative medicine. However, ES cells known as standard pluripotent cells have problem to be used for cell therapy because of ethical issue of the origin and immune response on the graft. Hence, recently reprogrammed pluripotent cells have been suggested as an alternative source for regenerative medicine. Somatic cells can acquire the ES cell-like pluripotency by transferring somatic cell nuclei into oocytes, by cell fusion with pluripotent cells. Retroviral-mediated introduction of four factors, Oct4, Sox2, Klf4 and c-Myc can successfully reprogram somatic cells into ES cell-like pluripotent stem cells, known as induced pluripotent stem (iPS) cells. These cells closely resemble ES cells in gene expression pattern, cell biologic and phenotypic characteristics. However, to reach the eventual goal of clinical application, it is necessary to overcome the major drawbacks such as low reprogramming efficiency and genomic alterations due to viral integration. In this review, we discuss the current reprogramming techniques and mechanisms of nuclear reprogramming induced by transcription factor transduction.

Aging of Stem and Progenitor Cells: Mechanisms, Impact on Therapeutic Potential, and Rejuvenation

“…Moreover, it is important to note that the elimination of technical constraints of reprogramming somatic cells also leads to rejuvenation of aged cells, such as differential gene expression profiles (genetic signatures), use of potentially harmful genome integrating viruses and induction of carcinogenesis, which remains a pending threat [90]. To this end, several numbers of strategies were recently developed: using the non-integrating adeno-and sendai-virus, plasmid vector, recombinant protein, or synthetic mRNA delivery [91]. Lapasset et This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip Platforms

“…First and foremost, differentiation efficiency highly depends on the quality of the iPS cells. There are several reprogramming methods with varying levels of pluripotency induction [94]. Somatic cell nuclear transfer (SCNT) into enucleated egg and somatic cell fusion with pluripotent stem cell methods create iPS cells more rapidly and efficiently than the revolutionary method of transducing cells with OCT3/4, SOX2, KLF4 and c-MYC (OSKM or Yamanaka factors) but are more technically challenging and pose ethical and safety issues [94].…”

“…There are several reprogramming methods with varying levels of pluripotency induction [94]. Somatic cell nuclear transfer (SCNT) into enucleated egg and somatic cell fusion with pluripotent stem cell methods create iPS cells more rapidly and efficiently than the revolutionary method of transducing cells with OCT3/4, SOX2, KLF4 and c-MYC (OSKM or Yamanaka factors) but are more technically challenging and pose ethical and safety issues [94]. The latter method can be performed with several different vectors [94] and requires appropriate stoichiometry of the four reprogramming factors to increase reprogramming efficacy where higher pluripotency induction rate can be achieved by increasing KLF4 [95] and OCT4 [95,96] or by decreasing SOX2 level [97].…”

“…Somatic cell nuclear transfer (SCNT) into enucleated egg and somatic cell fusion with pluripotent stem cell methods create iPS cells more rapidly and efficiently than the revolutionary method of transducing cells with OCT3/4, SOX2, KLF4 and c-MYC (OSKM or Yamanaka factors) but are more technically challenging and pose ethical and safety issues [94]. The latter method can be performed with several different vectors [94] and requires appropriate stoichiometry of the four reprogramming factors to increase reprogramming efficacy where higher pluripotency induction rate can be achieved by increasing KLF4 [95] and OCT4 [95,96] or by decreasing SOX2 level [97]. Although most iPS cell lines have been validated to express stem cell markers, form teratomas in mice and mimic the genetic and epigenetic status of embryonic stem cells, only a small subset of the iPS cell lines have been shown to achieve complete pluripotency as validated with tetraploid blastocyst complementation assay to produce live pups [90,98].…”

Current status of stem cell therapy: opportunities and limitations

“…An important resource for regenerative medicine is the reprogramming of mature somatic cells to become pluripotent by the manipulation of several factor expressions. Trying to understand and improve the molecular mechanisms of induced pluripotency, cell signaling pathways that control the reprogramming process have also been extensively studied, including LIF/ STAT3, PI3K/Akt, Wnt/β-catenin, TGFβ, and MAPK cascades (Kim et al, 2011;Hawkins et al, 2014).…”