Adipose tissue represents an abundant and accessible source of multipotent adult stem cells and is used by many investigators for tissue engineering applications; however, not all laboratories use cells at equivalent stages of isolation and passage. We have compared the immunophenotype of freshly isolated human adipose tissue-derived stromal vascular fraction (SVF) cells relative to serial-passaged adipose-derived stem cells (ASCs). The initial SVF cells contained colony-forming unit fibroblasts at a frequency of 1:32. Colony-forming unit adipocytes and osteoblasts were present in the SVF cells at comparable frequencies (1:28 and 1:16, respectively). The immunophenotype of the adipose-derived cells based on flow cytometry changed progressively with adherence and passage. Stromal cell-associated markers (CD13, CD29, CD44, CD63, CD73, CD90, CD166) were initially low on SVF cells and increased significantly with successive passages. The stem cell-associated marker CD34 was at peak levels in the SVF cells and/or early-passage ASCs and remained present, although at reduced levels, throughout the culture period. Aldehyde dehydrogenase and the multidrug-resistance transport protein (ABCG2), both of which have been used to identify and characterize hematopoietic stem cells, are expressed by SVF cells and ASCs at detectable levels. Endothelial cell-associated markers (CD31, CD144 or VE-cadherin, vascular endothelial growth factor receptor 2, von Willebrand factor) were expressed on SVF cells and did not change significantly with serial passage. Thus, the adherence to plastic and subsequent expansion of human adipose-derived cells in fetal bovine serum-supplemented medium selects for a relatively homogeneous cell population, enriching for cells expressing a stromal immunophenotype, compared with the heterogeneity of the crude SVF. STEM CELLS 2006;24:376 -385

These reviews of books and other forms of information express the opinions of the individual reviewers and are not necessarily endorsed by the Editorial Board of this Journal.

Regenerative medical techniques will require an abundant source of human adult stem cells that can be readily available at the point of care. The ability to use unmatched allogeneic stem cells will help achieve this goal.

Many acute and chronic conditions, such as acute kidney injury, chronic kidney disease, heart failure, and liver disease, involve mitochondrial dysfunction. Although we have provided evidence that drug-induced stimulation of mitochondrial biogenesis (MB) accelerates mitochondrial and cellular repair, leading to recovery of organ function, only a limited number of chemicals have been identified that induce MB. The goal of this study was to assess the role of the 5-hydroxytryptamine 1F (5-HT 1F ) receptor in MB. Immunoblot and quantitative polymerase chain reaction analyses revealed 5-HT 1F receptor expression in renal proximal tubule cells (RPTC). A MB screening assay demonstrated that two selective 5-HT 1F receptor agonists, LY334370 (4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide) and LY344864 (N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]-4-fluorobenzamide; 1-100 nM) increased carbonylcyanide-ptrifluoromethoxyphenylhydrazone-uncoupled oxygen consumption in RPTC, and validation studies confirmed both agonists increased mitochondrial proteins [e.g., ATP synthase b, cytochrome c oxidase 1 (Cox1), and NADH dehydrogenase (ubiquinone) 1b subcomplex subunit 8 (NDUFB8)] in vitro. Small interfering RNA knockdown of the 5-HT 1F receptor blocked agonistinduced MB. Furthermore, LY344864 increased peroxisome proliferator-activated receptor coactivator 1-a, Cox1, and NDUFB8 transcript levels and mitochondrial DNA (mtDNA) copy number in murine renal cortex, heart, and liver. Finally, LY344864 accelerated recovery of renal function, as indicated by decreased blood urea nitrogen and kidney injury molecule 1 and increased mtDNA copy number following ischemia/reperfusion-induced acute kidney injury (AKI). In summary, these studies reveal that the 5-HT 1F receptor is linked to MB, 5-HT 1F receptor agonism promotes MB in vitro and in vivo, and 5-HT 1F receptor agonism promotes recovery from AKI injury. Induction of MB through 5-HT 1F receptor agonism represents a new target and approach to treat mitochondrial organ dysfunction.

Fibroblasts are the effector cells of fibrosis characteristic of systemic sclerosis (SSc, scleroderma) and other fibrosing conditions. The excess production of extracellular matrix (ECM) proteins is the hallmark of fibrosis in different organs, such as skin and lung. Experiments designed to assess the pro-fibrotic capacity of factors, their signaling pathways, and potential inhibitors of their effects that are conducted in fibroblasts have paved the way for planning clinical trials in SSc. As such, fibroblasts have proven to be valuable tools in the search for effective anti-fibrotic therapies for fibrosis. Herein we highlight the characteristics of fibroblasts, their role in the etiology of fibrosis, utility in experimental assays, and contribution to drug development and clinical trials in SSc.