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| Strategy | Principle | Limitations |
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| Somatic cell nuclear transfer | The earliest example of experimentally induced reprogramming that involves the transfer of a somatic nucleus into an enucleated oocyte to produce cloned animals [22, 25]. | Low cloning efficiency, ethical problems, and observed abnormalities at different stages of development in test animals [26, 27]. |
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| Cell-cell fusion | Hybrid cells created by fusion of either mouse or human pluripotent cells with somatic cells, resulted in the reprogramming of the somatic genome to an embryonic state. The hybrid cells retained the characteristics of pluripotent cells [28, 29]. | Hindered by the resultant cell hybrids that are tetraploid [23, 29]. |
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| Exposed to extracts of pluripotent cells | Incubation of reversibly permeabilized cells with the cell-free extracts of pluripotent cells such as ESCs [24], embryonic germ cells [30], or Xenopus oocytes [31]. | The reprogrammed cells regain only some properties of pluripotent cells. We cannot properly exclude the possibility that the reexpression of pluripotency properties is due to material from the pluripotent cells in some cases [26]. |
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| Induced pluripotent stem cells | Reprogramming somatic cells back to an immature, pluripotent state by introduction of the pluripotent transcription factors [5, 6], by using protein transduction [32, 33], or by incubation with small molecules [34–36]. | Slow reprogramming process and low reprogramming efficiency [37]. The viral vectors may integrate into cell genome and in particular the oncogene c-Myc increases the risk of tumor formation [38, 39]. |
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