A challenge for regenerative medicine: Proper genetic programming, not cellular mimicry

Abstract

Recent progress in stem cell biology and the reprogramming of somatic cells to a pluripotent phenotype has generated a new wave of excitement in regenerative medicine. Nonetheless, efforts aimed at understanding transdifferentiation, dedifferentiation, and the plasticity of cells, as well as the ability of somatic cells to be reprogrammed, has raised as many questions as those that have been answered. This review proffers the argument that many reports of transdifferentiation, dedifferentiation, and unexpected stem cell plasticity may be due to aberrant processes that lead to cellular look-alikes (cellular mimicry). In most cases, cellular look-alikes can now be identified readily by monitoring gene expression profiles, as well as epigenetic modifications of DNA and histone proteins of the cells involved. This review further argues that progress in regenerative medicine will be significantly hampered by failing to address the issue of cellular look-alikes.

Prospectus of cultured meat—advancing meat alternatives

“…These DFAT cells are capable of being transdifferentiated into skeletal myocytes (Kazama et al 2008) and appear to be an attractive alternative to the use of stem cells. This process known as "ceiling culture method" certainly seems achievable on an industrial scale but Rizzino (2007) has put forth the argument that many of the claims of transdifferentiation, dedifferentiation and multipotency of once terminally differentiated cells may be due to abnormal processes resulting in cellular look-alikes.…”

Biomarkers for epithelial-mesenchymal transitions

“…By the mid-19th century, Raspail, Remak, and Virchow expanded this hypothesis by suggesting that all cells come from preexisting cells - the so-called cell theory. Although referring to cell division, this now classic notion is prescient of another contemporary twist in the biology of cell maturation: beyond lineage development and normal differentiation, mature epithelial cells under new environmental pressures exhibit a local plasticity that allows them to morph into other mature phenotypes with or without proliferation (2,3). Growing interest in the biology of these cellular transitions helped both establish epithelial cell plasticity as a field of study in the late 20th century and fashion much of the current thinking regarding morphogenesis in early embryonic development, tissue repair, and cancer metastasis (4)(5)(6).…”

Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells

“…Therefore, standard parameters which may be used in parallel to characterize the outcome of differentiation experiments may comprise: expression of key liver-specific transcription factors (e.g., HNF-4α, HNF-3γ, HNF-6, GATA-6) to evaluate the genetic reprogramming of cells [99][100][101]; evaluation of glycogen storage capacity (eg, visualized by PAS staining procedure) (Fig. 1) [89,102]; ammonia metabolism and urea production (determined by colorimetric or fluorometric assays) [102][103][104]; selective uptake of vital stains (eg, indocyanine green, which is uptaken exclusively by hepatocytes) [105]; secretion of plasma proteins (eg, albumin) [106,107].…”