Fundamentals of Stem Cells: Why and How Patients' Own Adult Stem Cells Are the Next Generation of Medicine

Abstract

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent

“…It should be pointed out that a major shortcoming of this definition of multipotent MSCs is the fact that, for example, fibroblasts are also adherent to plastic and express the surface markers CD73, CD90 and CD105, without having the ability to transdifferentiate into other lineages or being MSCs [71]. Furthermore, the true pluripotent stem cells do not yet express CD73, CD90 and CD105 [76]. Rather, expression of cell surface markers is a dynamic process.…”

“…Rather, expression of cell surface markers is a dynamic process. For example, when cultured in fetal bovine serum or platelet lysate culture media, MSCs can turn on new surface markers [76]. Alternatively, MSCs in culture can lose their surface marker expression, such as for example the loss of the previously expressed progenitor marker CD34 or the endothelial progenitor marker CD31 [76].…”

Isolation of adipose tissue derived regenerative cells from human subcutaneous tissue with or without the use of an enzymatic reagent

“…It should be pointed out that a major shortcoming of this definition of multipotent MSCs is the fact that, for example, fibroblasts are also adherent to plastic and express the surface markers CD73, CD90 and CD105, without having the ability to transdifferentiate into other lineages or being MSCs [69]. Furthermore, the true pluripotent stem cells do not yet express CD73, CD90 and CD105 [73]. Rather, expression of cell surface markers is a dynamic process.…”

“…Rather, expression of cell surface markers is a dynamic process. For example, when cultured in fetal bovine serum or platelet lysate culture media, MSCs can turn on new surface markers [73]. Alternatively, MSCs in culture can lose their surface marker expression, such as for example the loss of the previously expressed progenitor marker CD34 or the endothelial progenitor marker CD31 [73].…”

Safety and Efficacy of Treating Symptomatic, Partial-Thickness Rotator Cuff Tear with Fresh, Uncultured, Unmodified, Autologous Adipose Derived Regenerative Cells (UA-ADRCs) Isolated at Point of Care: A Prospective, Randomized, Controlled First-in-Human Pilot Study

“…Recent studies demonstrate the advantages of newer proprietary methods for harvesting and isolating stem cells [18][19][20][21]. The present study evaluated the safety and efficacy of treating sPTRCT which did not respond to traditional nonoperative care for six weeks with a single injection of UA-ADRCs isolated at point of care.…”