Novel non-tumorigenic human pluripotent stem cells isolated from adipose tissue (Muse-AT cells): new paradigm in regenerative medicine.

CHAZENBLAK, GD; GIMENO, ML; PERONE, MJ

Las Vegas

Congreso; 16th Annual Meeting IFATS; 2018

Significant progress has occurred since Multi-Lineage Differentiating Stress Enduring cells isolated from adipose tissue (Muse-AT) cells, a novel human non-tumorigenic pluripotent stem cells, were introduce to the scientific community in 2013. Muse-AT cells can be obtained under severe cellular stress conditions such as lack of nutrients, hypoxia, long collagenase treatment, and low temperatures. Muse-AT cell expansion is not required due to the abundance of highly purified Muse-AT cells obtained (25-50 million cells /100 gr of lipoaspirate material). Muse-AT cells are present in both adipocyte and stromal vascular fractions. Additionally, the purification of Muse-AT cells does not require cell sorting, magnetic beads, or special devices. Muse-AT cells grow in suspension as cell clusters, expressing the classical pluripotent stem cell markers SSEA3/4, NANOG, Oct3/4, and Sox2, although in much lower levels than relative to embryonic stem cells (ES) or induced pluripotent stem cells (iPS). Furthermore, Muse-AT cells can spontaneously or induced differentiate into the three germ cell layers. Muse-AT cells preferentially spontaneously differentiate into adipocytes, indicating that they retain an epigenetic memory, of their tissue of origin. Importantly, Muse-AT cells do not undergo tumorigenesis or form teratomas "in vivo". Additionally, the microRNA Let-7 seems to be a critical master regulator of Muse-AT proliferation without teratogenesis. Muse-AT cells also display a stable normal karyotype in culture, as indicated by their normal chromosome number and integrity. Muse-AT cells highly express significant amounts of TGF-beta1, a key cytokine governing down-modulation of T lymphocytes and macrophages. Furthermore, Muse-AT cells have immunomodulatory properties mediated by their secretion of specific cytokines/growth factors. Our preliminary results indicate the beneficial effects of Muse-AT cells in an experimental mice model of type 1 diabetes. Because naive Muse-AT cells are normally in a quiescent state, they are innate resilient to severe cellular stress and therefore can survive when transplanted back into the host organism. All these qualities and vast potential make Muse-AT cells an "optimal" candidate for tissue regeneration and stem cell therapy.