A mystery unraveled: nontumorigenic pluripotent stem cells in human adult tissues

Abstract

Introduction: Embryonic stem cells and induced pluripotent stem cells have emerged as the gold standard of pluripotent stem cells and the class of stem cell with the highest potential for contribution to regenerative and therapeutic application; however, their translational use is often impeded by teratoma formation, commonly associated with pluripotency. We discuss a population of nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress Enduring (Muse) cells, which offer an innovative and exciting avenue of exploration for the potential treatment of various human diseases. Areas covered: This review discusses the origin of Muse cells, describes in detail their various unique characteristics, and considers future avenues of their application and investigation with respect to what is currently known of adult pluripotent stem cells in scientific literature. We begin by defining cell potency, then discuss both mesenchymal and various reported populations of pluripotent stem cells, and finally delve into Muse cells and the characteristics that set them apart from their contemporaries. Expert opinion: Muse cells derived from adipose tissue (Muse-AT) are efficiently, routinely and painlessly isolated from human lipoaspirate material, exhibit tripoblastic differentiation both spontaneously and under media-specific induction, and do not form teratomas. We describe qualities specific to Muse-AT cells and their potential impact on the field of regenerative medicine and cell therapy.

Behavior ofIn SituHuman Native Adipose TissueCD34+ Stromal/Progenitor Cells During Different Stages of Repair. Tissue‐ResidentCD34+ Stromal Cells as a Source of Myofibroblasts

“…Recently, Dezawa et al have identified a type of pluripotent mesenchymal stem cell, which they named multilineage‐differentiating stress‐enduring (Muse) cells (Kuroda et al, ; Wakao et al, ; Kuroda and Dezawa, ). These cells have attracted considerable attention to regenerative medicine (Simerman et al, , b). Under cellular stress conditions, Muse cells were isolated from human bone marrow and dermal fibroblasts (Kuroda et al, ), as well as from adipose tissue harvested by lipoaspiration (Muse‐adipose tissue cells‐Muse AT cells) (Heneidi et al, ).…”

Dedifferentiated Fat (DFAT) cells: A cell source for oral and maxillofacial tissue engineering

“…The original protocol to generate iPSCs (Takahashi, Okita, Nakagawa, & Yamanaka, 2007) used the c-Myc oncogene as one of the reprogramming factors and a retroviral vector for gene transfer; this raises concerns for potential tumorigenesis. There is also a risk of teratoma formation with the transplantation of undifferentiated iPSCs (Simerman, Perone, Gimeno, Dumesic, & Chazenbalk, 2014;Takahashi, & Tanabe et al, 2007). We believe that dedifferentiated fat (DFAT) cells have the potential to solve some of the limitations inherent to the use of BMSCs, ASCs, DPSCs, PDLSCs, and iPSCs.…”

Trehalose preincubation increases mesenchymal (CD271⁺) stem cells post-cryopreservation viability

“…[5][6][7] Mesenchymal stem cell is a heterogeneous population recently discovered to contain not only multipotent stem cell but also non-tumorigenic pluripotent stem cell subpopulation known as the multi-lineage differentiating stress enduring (MUSE) cells. 8,9 The ability to preserve functional properties of such unique subpopulation will greatly contribute to the development of regenerative medicine.…”