Induced pluripotent stem cells: advances to applications

Figures & data

Figure 1 Bioengineering stem cells. Therapeutic cloning with the advent of somatic cell nuclear transfer has allowed bioengineering processes to create pluripotent stem cells derived with the genetic identity of a somatic cell nucleus. The technique requires a natural embryonic host environment to induce reprogramming of the transplanted, non-stem cell nucleus. Full conversion enables the production of cloned blastocysts that are capable of providing embryonic stem cells for therapeutic purposes. Alternatively, nuclear reprogramming has been streamlined to be efficient with a minimal set of stemness related genes that can be introduced ectopically in order to recapitulate full reprogramming without the requirements of any embryonic tissue source. Collectively, autologous pluripotent stem cells are generated that have acquired the fate of stem cells and are able to give rise to all mature tissues and cell types. Bioengineered stem cells offer unprecedented opportunities for discovery, diagnostics, and therapeutics to advance personalized cell-based platforms.

Table 1 Pluripotent stringency criteria

Pluripotent stringency
Mouse model systems	Human model systems
In vitro morphology and gene expression	In vitro morphology and gene expression
In vivo teratoma formation	In vivo teratoma formation
In utero chimeric embryogenesis	Not applicable
Tetraploid aggregation and germline transmission	Not applicable

Table 2 Strategies for nuclear reprogramming through ectopic gene delivery

Pluripotent induction
Genomic modification	Genomic modification-free
Retrovirus delivery	Cre recombinase
Lentivirus delivery	Transposon-transposase systems
Stable integration-drug selection	Adenovirus delivery
Homologous gene targeting	Plasmid-episome transduction

Table 3 Models of disease treated with iPS-based interventions

iPS-based therapy
Disease condition	Therapeutic outcome
Sickle cell disease	Hematopoiesis, functional physiological improvement
Parkinson’s disease	Dopamine production, symptomatic improvement
Hemophilia A	Decreased clotting time, survival benefit
Ischemic heart disease	Improved cardiac performance, in situ tissue repair