scholarly journals Insights from a Chimpanzee Adipose Stromal Cell Population: Opportunities for Adult Stem Cells to Expand Primate Functional Genomics

2013 ◽  
Vol 5 (10) ◽  
pp. 1995-2005 ◽  
Author(s):  
L. W. Pfefferle ◽  
G. A. Wray
Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4268-4268 ◽  
Author(s):  
Lilia Stepanova ◽  
Brian Sorrentino

Abstract There is now accumulating evidence for the existence of rare cancer stem cells that resemble adult stem cells in their ability to replicate and produce more specialized cells constituting the bulk of the tumor. Neuroblastoma is the most common childhood cancer, developing extracranially from neuroblasts of the body. Approximately 70–80% of patients have metastatic disease at the time of diagnosis, and fewer than half of these patients are cured. Human neuroblastoma cells have been shown to contain a subpopulation of cells with a high capacity to efflux Hoechst 33342 nuclear dye, resulting in a distinct side population (SP) phenotype (Hirschmann-Jax et al., PNAS, 2004). These SP cells also express high levels of ABCG2 and ABCA3 transporter genes. We have used a mouse model to further investigate the relationship between the SP phenotype and Abcg2 expression in neuroblastoma stem cells. Mice, expressing N-myc in neural-crest cells, develop neuroblastomas at early age (Weiss et al., EMBO J, 1997). We have found that these neuroblastomas can be divided into three groups according to their SP phenotype; no SP cells present, low SP cells (0.6–2% of total cell number) and high SP cells (20–40% SP cells in total neuroblastoma cell population). When present, the SP fraction was significantly decreased after treatment of the cells with gleevec and fumitremorgin C, inhibitors of Abcg2 function ( 4.7% with treatment vs. 30.5% untreated in one case). This result indicates that Abcg2 is a major determinant of SP phenotype in these tumors. Quantitative PCR, performed on sorted SP and non-SP cells confirmed about 6 fold higher level of Abcg2 expression in the SP cell fraction in comparison with non-SP. In order to determine the clonogenic capacity of different tumor cell populations, varying numbers of tumor cells were injected in the flanks of NOD/SCID/gamma null mice. Transplantability of the tumors was found to correlate with SP phenotype. At a dose of 106 cells per recipient, neuroblastomas with no SP cells did not form tumors (0 tumors developed in 6 recipients). Neuroblastoma cells with low SP cell numbers (0.6% of total cells) formed tumors in 2 out of 4 transplants at this cell dose. Neuroblastomas with a high SP cell population (30% of the cells) had the highest clonogenic activity, forming tumors in 6 out of 6 transplants at 106 cells per injection. These results indicate that tumor stem cells are more abundant in high SP tumors in comparison with tumors with lower SP cell fractions. Next, sorting experiments based on the SP phenotype indicated that SP cells are enriched for neuroblastoma stem cells. In one experiment using a neuroblastoma sample with 22% SP cells, recipients were inoculated with a dose of 105 sorted cells. Three out of 4 mice formed tumors after transplantation with sorted SP cells while only 1 of 4 mice transplanted with non-SP cells developed tumors. Secondary tumors, developed from sorted SP cells, had themselves higher proportion of SP cells in comparison with tumors, developed from non-SP cells (35–40% and 8–10%, respectively). We are now using this genetic mouse model to further study the use of Abcg2 expression to isolate neuroblastoma stem cells.


2002 ◽  
Vol 13 (12) ◽  
pp. 4279-4295 ◽  
Author(s):  
Patricia A. Zuk ◽  
Min Zhu ◽  
Peter Ashjian ◽  
Daniel A. De Ugarte ◽  
Jerry I. Huang ◽  
...  

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.


1990 ◽  
Vol 171 (5) ◽  
pp. 1547-1565 ◽  
Author(s):  
G Van Zant ◽  
B P Holland ◽  
P W Eldridge ◽  
J J Chen

We have studied contributions to hematopoiesis of genetically distinct stem cell populations in allophenic mice. Chimeras were made by aggregating embryos of inbred strains known to differ with respect to stem cell population kinetics. One partner strain (DBA/2) has previously been shown to normally have a stem cell (CFU-S) population of which 24% are in S-phase of the cell cycle, whereas the homologous population of the other partner strain (C57BL/6) was characterized by having only 2.6% in cycle (7). Contributions of the chimeric stem cell population to mature blood cell pools were studied throughout the life of the mice and intrinsic differences in stem cell function and aging were reflected in dynamic patterns of blood cell composition. The DBA/2 stem cell population was eclipsed by stem cells of the C57BL/6 genotype and, after 1.5-3 yr, the hemato-lymphoid composition of 22 of 27 mice studied for this long had shifted by at least 25 percentage points toward the C57BL/6 genotype. 8 of the 27 had hematolymphoid populations solely of C57BL/6 origin. To test whether or not a population of stem cells with an inherently higher cycling rate (DBA/2) might have a competitive advantage during repopulation, we engrafted allophenic marrow into lethally irradiated (C57BL/6 x DBA/2)F1 recipients. DBA/2 hematopoiesis was predominant early, far outstripping its representation in the marrow graft. Perhaps as a consequence of inherently greater DBA/2 stem cell proliferation, the populations of developmentally more restricted precursor populations (CFU-E, BFU-E, CFU-GM, CFU-GEMM) showed an overwhelming DBA/2 bias in the first 2-3 mo after engraftment. However, as in the allophenic mice themselves during the aging process, the C57BL/6 genotypic representation was ascendant over the subsequent months. The shift toward C57BL/6 genotype was first documented in the marrow and spleen precursor cell populations and was subsequently reflected in the circulating, mature blood cells. Bone marrow-derived stromal cell cultures from engrafted mice were studied and genotypic analyses showed donor representation in stromal cell populations that reflected donor hematopoietic contributions in the same recipient. Results from these studies involving two in vivo settings (allophenic mice and engraftment by allophenic marrow) are consistent with the notion that a cell autonomous difference in stem cell proliferation confers on one population a competitive repopulating advantage, but at the expense of longevity.


2017 ◽  
Vol 8 ◽  
pp. 204173141770561 ◽  
Author(s):  
Hannah Donnelly ◽  
Carol-Anne Smith ◽  
Paula E Sweeten ◽  
Nikolaj Gadegaard ◽  
RM Dominic Meek ◽  
...  

Adult stem cells, such as mesenchymal stem cells, are a multipotent cell source able to differentiate towards multiple cell types. While used widely in tissue engineering and biomaterials research, they present inherent donor variability and functionalities. In addition, their potential to form multiple tissues is rarely exploited. Here, we combine an osteogenic nanotopography and a chondrogenic hyaluronan hydrogel with the hypothesis that we can make a complex tissue from a single multipotent cell source with the exemplar of creating a three-dimensional bone–cartilage boundary environment. Marrow stromal cells were seeded onto the topographical surface and the temperature gelling hydrogel laid on top. Cells that remained on the nanotopography spread and formed osteoblast-like cells, while those that were seeded into or migrated into the gel remained rounded and expressed chondrogenic markers. This novel, simple interfacial environment provides a platform for anisotropic differentiation of cells from a single source, which could ultimately be exploited to sort osteogenic and chondrogenic progenitor cells from a marrow stromal cell population and to develop a tissue engineered interface.


Author(s):  
Ratan K Choudhary ◽  
Fenq-Qi Zhao

: Adult stem cells like mammary and mesenchymal stem cells have received significant attention because these stem cells (SCs) possess therapeutic potential in treating many animal diseases. These cells can be administered in an autologous or allogenic fashion, either freshly isolated from the donor tissue or previously cultured and expanded in vitro. Expansion of adult stem cells is a prerequisite before therapeutic application because sufficient numbers are required in dosage calculation. Stem cells directly and indirectly (by secreting various growth factors and angiogenic factors called secretome) act to repair and regenerate injured tissues. Recent studies on mammary stem cells showed in vivo and in vitro expansion ability by removing the blockage of asymmetrical cell division. Compounds like purine analogs (xanthosine, xanthine, and inosine) or hormones (progesterone and bST) help increase stem cell population by promoting cell division. Such methodology of enhancing stem cells number, either in vivo or in vitro, may help in preclinical studies for translational research like treating diseases like mastitis. The application of mesenchymal stem cells has also been shown to benefit mammary gland health due to the ‘homing’ property of stem cells. In addition to that, the multiple positive effects of stem cell secretome are on mammary tissue healing and killing bacteria is novel in the production of quality milk. This systematic review discusses some of the studies on stem cells that have been useful in increasing the stem cell population and increasing mammary stem/progenitor cells. Finally, we provide insights into how enhancing mammary stem cell population could potentially increase terminally differentiated cells, ultimately leading to more milk production.


2005 ◽  
Vol 53 (S 3) ◽  
Author(s):  
W Röll ◽  
T Hashemi ◽  
M Breitbach ◽  
O Dewald ◽  
A Welz ◽  
...  

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