Stem Cell Platforms for Regenerative Therapy

Stem cells have a unique aptitude to differentiate into specialized cell types and form new tissue, thus providing the active ingredient of regenerative therapy. Application of therapeutic repair starts with the use of standardized stem cell-based platforms such as the increasingly established embryonic, perinatal, and adult stem cell sources and their cell progeny derivatives. Embryonic stem cells have the advantage of an unequaled pluripotent differentiation plasticity associated with a robust repair capacity, yet access for clinical applications remains a significant limitation, along with a risk of uncontrolled growth and immunological intolerance. While methods for lineage restriction are increasingly developed and validated, the adult stem cells hematopoietic or mesenchymal in origin have the benefit of autologous immunologic status and are readily available for clinical applications, although the induction of reliable tissue-specific differentiation remains a possible limitation. Perinatal stem cells incorporate advantageous characteristics from both embryonic and adult stem cells, including potential autologous status and broader differentiation capacity than adult stem cells, and provide the most available stem cell source when harvested at birth.

Alternatively, bioengineered platforms, including therapeutic cloning and nuclear reprogramming, further offer generation of hybrid cells and tissues. In this context, enabling biotechnology platforms have most recently emerged to create hybridized stem cell types designed to systematically address cell characteristics that currently limit the clinical translation of more standard cell-based therapeutics. Exploiting genetic and epigenetic factors to regulate phenotypic outcomes, the biotechnology platforms achieve guided genetic reprogramming of adult cells back to an embryonic-like state (induced pluripotent stem cell). These platforms bypass the need for embryo extraction to generate categorical pluripotent stem cell phenotypes and recycle somatic nuclei to form autologous, immunotolerant cell-based products. Reprogramming of the adult stem cells to generate customized embryonic-like stem cells offers, thereby, an attractive tool to engineer patient-specific regenerative therapies.

Somatic cell nuclear transfer (SCNT) allows transacting factors present within the mammalian oocytes to reprogram somatic cell nuclei to an undifferentiated state. Therapeutic cloning refers to SCNT in which the nuclear content of a somatic cell from an individual is transferred into an enucleated donor egg to derive blastocysts that contain pluripotent embryonic-like stem cells. In this way, SCNT has produced cloned ESCs from multiple mammalian somatic cell biopsies. The pluripotency of derived cells has been confirmed through germline transmission and reproductive cloning.