Since the advent of modern stem cell biology and the discovery of embryonic stem cells, there has been growing interest in adult stem cells.  First, these cells avoid ethical & religious objections since these cells are not derived from embryos. Secondly, clinical studies of adult stem cells have provided evidence of safety and efficacy, especially for osteoarthritis, tendinitis, muscle injury, etc.   A recent publication provides a new method using cellular stress to select & purify pluripotent stem cells from cells derived from adipose tissue removed from the body by liposuction.  The pluripotent stem cells in fat are known as Muse (multi-differentiating stress-enduring) cells, and comprise a small but significant portion of adult fibroblasts, adipose-derived SCs (ASC) and possibly other adult stem cell populations.  These cells spontaneously form the three germ layers, mesoderm, ectoderm and endoderm and can be treated to form induced pluripotent SCs (iPSCs) that are functionally equivalent to embryonic stem cells.  There is evidence for the selective conversion of Muse to iPSCs cells in human fibroblast cells while non-Muse cells were not reprogrammable.  This latter observation supports the Elite hypothesis of iPSC generation as opposed to an alternative Stochastic hypothesis where any cell type may be reprogrammed to iPSCs (Wakao, et al, PNAS 108: 9875, 2011).

           Adult stem cells frequently have a low survival rate when transplanted for cell therapy. This may be due to the cellular stress environment that the cells face after transplantation. Because the environment of the damaged tissue cannot be changed to improve the post-transplant cell survival rate, one solution is to gradually adapt the stem cells to cellular stress prior to cell delivery.   Harvesting human adipose tissue by liposuction is routine clinical procedure.  There are several studies of safety and efficacy showing clinical promise of the transplantation of fat-derived MSCs for treatment of various human and animal conditions.  A group led by Saleh Heneidi at Georgetown University showed that  a combination of stressors, particularly: reduced oxygen, reduced temperature and serum deprivation, selected  Muse cells that express pluripotent stem cell markers and can spontaneously differentiate into mesenchymal, endodermal, and ectodermal cell lineages with an efficiency of approximately 20% for each type.   While adipose MSCs required approximately two and a half weeks to develop into mature adipocytes, Muse cells differentiated substantially by day 6.  Also, Muse cells migrate to damaged tissue sites and spontaneously differentiate into tissue specific cells according to the microenvironment to contribute to tissue regenerating when infused into the blood stream.

            This research shows that cellular stress can be used to isolate pluripotent stem cells from human adipose tissue. These cells differentiate quickly and into many different types of cells. Because these cells are highly resistant to severe cellular stress, they have the potential to make a substantial impact on the field of regenerative medicine.  Furthermore, these cells may be readily reprogrammed to iPSCs that are pluripotent thus expanding the cell therapy indications to include repair or regeneration of any cell type.  Such cells may be either autologous, personalized cells or allogeneic, allowing GMP-compliant manufacturing under highly controlled conditions and approval by regulatory agencies.  In an ironic twist of the long-standing debate regarding adult verses embryonic stem cells, the functional equivalent of embryonic stem cells may be readily available and easily isolated from adult tissues as this current research suggests. 


By Lianne Nelsen, Chemical Engineering student, Colorado School of Mines & Research Technician, Vitro Biopharma and Jim Musick, Ph. D. President and CEO Vitro Biopharma