Clonal Multilineage Differentiation of Murine Common Pluripotent Stem Cells Isolated from Skeletal Muscle and Adipose Stromal Cells

Abstract

Pluripotent stem cells (PSCs) with transdifferentiation capacity may provide useful therapeutic modalities in the areas of cellular restoration and regenerative medicine. The utility of PSCs depends on their ability to respond to different stimuli and to adapt to tissue-specific differentiation conditions. Given that a number of cells possessing characteristics of PSCs have been identified and isolated from several adult murine tissues, we hypothesized that a common PSC may exist in multiple murine tissues and that these cells may either reside permanently in specific sites or continue to circulate and colonize tissues as needed. Previous data from our laboratory suggest that PSCs exhibiting an immunophenotype of CD45(-)Sca-1(+)c-kit(-)Thy-1(+) can be isolated from multiple murine tissues and may represent putative common PSCs (CoPSCs). To investigate whether the multiple tissue differentiation potential observed with these cells resulted from the presence of different tissue-restricted progenitors within CD45(-)Sca-1(+)c-kit(-)Thy-1(+) cells or was the product of clonal differentiation of CoPSCs, clonality studies were performed. Single skeletal muscle (SM)-derived CoPSCs were expanded for 10 days, and progeny cells were split into three culture conditions designed to stimulate myogenic, adipogenic, and neurogenic differentiation. Analysis of 600 clones indicated that 2.16%, 0.83%, and 0.33% of the total number of plated single cells were capable of unipotent, bipotent, and tripotent differentiation, respectively, into combinations of myocytes, adipocytes, and neuronal cells. Given that SM-derived CoPSCs represent 4.78% of the total cells analyzed, tripotent CoPSCs made up 0.016% of the total muscle cells. Similar results were obtained in clonal analyses using adipose stromal cell (ASC)-derived CoPSCs, suggesting that both SM- and ASC-derived CoPSCs may be phenotypically and functionally identical. Taken together, these data demonstrate that a common PSC can be identified in different murine tissues and suggest that a small fraction of these cells are capable of clonal differentiation into multiple cell types.

A Population of Multipotent CD34-Positive Adipose Stromal Cells Share Pericyte and Mesenchymal Surface Markers, Reside in a Periendothelial Location, and Stabilize Endothelial Networks

“…This study demonstrates for the first time that stromal cells derived from subcutaneous adipose tissue, which have properties of preadipocytes 12,15,31 and manifest clonal pluripotency along multiple lineage pathways, 15,32,33 serve structurally and functionally as pericytes within adipose tissue. This finding sheds a unique light on their importance in normal adipose biology as well as the biological basis for their ability to promote vascularization and accelerate tissue perfusion in the context of ischemia.…”

Adipocytes as Immune Cells: Differential Expression of TWEAK, BAFF, and APRIL and Their Receptors (Fn14, BAFF-R, TACI, and BCMA) at Different Stages of Normal and Pathological Adipose Tissue Development

“…Similarities in surface marker profiles, morphology, and differentiation potentials assayed in vitro led to suggestions that each of these multipotent cell types arise from a common adult progenitor cell (37) and then may adopt tissue-specific attributes according to its particular niche (38). Adipose tissue represents a rich source of such cells.…”

Differentiation of Human Adipose-Derived Stem Cells into Neuron-Like Cells Which Are Compatible with Photocurable Three-Dimensional Scaffolds

“…5,6 In the past 5 years, the differentiation of hADSCs into neuron cells has attracted much attention from scientists and clinicians of translational medicine because of their potential clinical application in neurodegenerative diseases, such as Parkinson and Alzheimer diseases. [7][8][9][10][11][12][13][14][15][16][17][18][19] Previous studies are typically involved in the evaluation and mechanism of in vitro neuronal differentiation of hADSCs or hBMSCs rather than their clinical translation. For hADSC clinical application to treat neural degeneration or related diseases, it is essential to create an optimal niche to ensure the viability of transplanted cells and to promote them in vivo proliferation and differentiation of hADSCs.…”