| Slowed progression in models of huntington disease by adipose stem cell transplantation.
November 26, 2009 at 8:00 am
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| | Slowed progression in models of huntington disease by adipose stem cell transplantation. Ann Neurol. 2009 Jun 29;66(5):671-681 Authors: Lee ST, Chu K, Jung KH, Im WS, Park JE, Lim HC, Won CH, Shin SH, Lee SK, Kim M, Roh JK OBJECTIVE: Adipose-derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models. METHODS: ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)-induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60-day-old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we treated mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media. RESULTS: In the QA model, human ASCs reduced apomorphine-induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota-Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC-transplanted R6/2 mice expressed elevated levels of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1alpha expression. INTERPRETATION: Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671-681. PMID: 19938161 [PubMed - as supplied by publisher] |
| Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue.
November 26, 2009 at 8:00 am
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| | Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue. Cytotherapy. 2009;11(8):1052-64 Authors: Jurgens WJ, van Dijk A, Doulabi BZ, Niessen FB, Ritt MJ, van Milligen FJ, Helder MN Background aims Stem cell therapies are being evaluated as promising alternatives for cartilage regeneration. We investigated whether stromal vascular fraction cells (SVF) from the infrapatellar (Hoffa) fat pad are suitable for a one-step surgical procedure to treat focal cartilage defects. Methods SVF was harvested from patients undergoing knee arthroplasty (n = 53). Colony-forming unit (CFU) assays, growth kinetics and surface marker profiles were determined, and the chondrogenic differentiation capacity of freshly isolated SVF was assessed after seeding in three-dimensional poly (l-lactic-co--caprolactone) scaffolds. Results SVF yield per fat pad varied between 0.55 and 16 x 10(6) cells. CFU frequency and population doubling time were 2.6 +/- 0.6% and +/-2 days, respectively. Surface marker profiles matched those of subcutaneous-derived adipose-derived stem cells (ASC). CFU from Hoffa SVF showed differentiation toward osteogenic and adipogenic lineages. Cartilage differentiation was confirmed by up-regulation of the cartilage genes sox9, aggrecan, collagen type II and cartilage oligomeric matrix protein (COMP), collagen II immunostaining, Alcian Blue staining and glycosaminoglycan production. Compared with passaged cells, SVF showed at least similar chondrogenic potential. Conclusions This study demonstrates that SVF cells from the infrapatellar fat pad are suitable for future application in a one-step surgical procedure to regenerate cartilage tissue. SVF shows similar favorable characteristics as cultured ASC, and chondrogenic differentiation even appears to be slightly better. However, because of variable harvesting volumes and yields, SVF from the infrapatellar fat pad might only be applicable for treatment of small focal cartilage defects, whereas for larger osteoarthritic defects subcutaneous adipose tissue depot would be preferable. PMID: 19929469 [PubMed - in process] |
| Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in inflammatory bowel disease.
November 26, 2009 at 8:00 am
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| | Isolation of stem cell populations with trophic and immunoregulatory functions from human intestinal tissues: potential for cell therapy in inflammatory bowel disease. Cytotherapy. 2009;11(8):1020-31 Authors: Lanzoni G, Alviano F, Marchionni C, Bonsi L, Costa R, Foroni L, Roda G, Belluzzi A, Caponi A, Ricci F, Luigi Tazzari P, Pagliaro P, Rizzo R, Lanza F, Roberto Baricordi O, Pasquinelli G, Roda E, Paolo Bagnara G Background aims Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSC) are currently under evaluation in phase III clinical trials for inflammatory bowel disease and other intestinal disease manifestations. The therapeutic efficacy of these treatments may derive from a combination of the differentiation, trophic and immunomodulatory abilities of the transplanted cells. We investigated intestinal tissues as sources of MSC: such cells may support tissue-specific functions and hold advantages for engraftment and contribution in the gastrointestinal environment. Methods Intestinal specimens were collected, and the mucosa and submucosa mechanically separated and enzymatically digested. Mesenchymal stromal populations were isolated, expanded and characterized under conditions commonly used for MSC. The differentiation potential, trophic effect and immunomodulatory ability were investigated. Results We successfully isolated and extensively expanded populations showing the typical MSC profile: CD29(+), CD44(+), CD73(+), CD105(+) and CD166(+), and CD14(-), CD34(-) and CD45(-). Intestinal mucosal (IM) MSC were also CD117(+), while submucosal cultures (ISM MSC) showed CD34(+) subsets. The cells differentiated toward osteogenic, adipogenic and angiogenic commitments. Intestinal-derived MSC were able to induce differentiation and organization of intestinal epithelial cells (Caco-2) in three-dimensional collagen cultures. Immunomodulatory activity was evidenced in co-cultures with normal heterologous phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusions Multipotent MSC can be isolated from intestinal mucosal and submucosal tissues. IM MSC and ISM MSC are able to perform trophic and immunomodulatory functions. These findings could open a pathway for novel approaches to intestinal disease treatment. PMID: 19929466 [PubMed - in process] |
| Human adipose-derived mesenchymal stem cells in vitro: evaluation of an optimal expansion medium preserving stemness.
November 26, 2009 at 8:00 am
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| | Human adipose-derived mesenchymal stem cells in vitro: evaluation of an optimal expansion medium preserving stemness. Cytotherapy. 2009 Nov 24; Authors: Baer PC, Griesche N, Luttmann W, Schubert R, Luttmann A, Geiger H Background aims. The potential of cultured adipose-derived stem cells (ASC) in regenerative medicine and new cell therapeutic concepts has been shown recently by many investigations. However, while the method of isolation of ASC from liposuction aspirates depending on plastic adhesion is well established, a standard expansion medium optimally maintaining the undifferentiated state has not been described. Methods. We cultured ASC in five commonly used culture media (two laboratory-made media and three commercially available media) and compared them with a standard medium. We analyzed the effects on cell morphology, proliferation, hepatocyte growth factor (HGF) expression, stem cell marker profile and differentiation potential. Proliferation was measured with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a fluorescent assay. Release of HGF was assessed by an immunoassay. Expression of characteristic stem cell-related transcription factors and markers was evaluated by quantitative polymerase chain reaction (qPCR) (Nanog, Sox-2, Rex-1, nestin and Oct-4) and flow cytometry (CD44, CD73, CD90, CD105 and CD166), and differentiation was shown by adipogenic medium. Results. The morphology and expansion of ASC were significantly affected by the media used, whereas none of the media influenced the ASC potential to differentiate into adipocytes. Furthermore, two of the media induced an increase in expression of transcription factors, an increased secretion of HGF and a decrease in CD105 expression. Conclusions. Culture of ASC in one of these two media before using the cells in cell therapeutic approaches may have a benefit on their regenerative potential. PMID: 19929458 [PubMed - as supplied by publisher] |
| Anti-L-NGFR and -CD34 Monoclonal Antibodies identify multipotent mesenchymal stem cells in human adipose tissue.
November 26, 2009 at 8:00 am
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| | Anti-L-NGFR and -CD34 Monoclonal Antibodies identify multipotent mesenchymal stem cells in human adipose tissue. Stem Cells Dev. 2009 Nov 23; Authors: Quirici N, Scavullo C, de Girolamo L, Lopa S, Arrigoni E, Lambertenghi Deliliers G, Brini AT Stem cells hold great promise in tissue engineering for repairing tissues damaged by disease or injury. Mesenchymal stem cells (MSCs) are multipotent cells able to proliferate and differentiate into multiple mesodermal tissues such as bone, cartilage, muscle, tendon and fat. We have previously reported that the low-affinity nerve growth factor receptor (L-NGFR or CD271) defines a subset of cells with high proliferative, clonogenic and multipotential differentiation ability in adult bone marrow (BM). It has been recently shown that adipose tissue is an alternative source of adult multipotent stem cells and human adipose-derived stem cells, selected by plastic-adherence (PA hASCs), have been extensively characterized for their functional potentials in vitro. In this study, immuno-selected L-NGFR+ and CD34+ subpopulations have been analyzed and compared with the PA hASCs. Phenotypic profile of freshly purified subpopulations showed an enrichment in the expression of some stem cell markers: indeed, a great percentage of L-NGFR+ cells co-expressed CD34 and CD117 antigens, whereas the endothelial-committed progenitor markers KDR and P1H12 were mainly expressed on CD34+ cells. Differently from PA hASCs, the immuno-separated fractions showed high increments in cell proliferation, and the fibroblast colony-forming activity (CFU-F) was maintained throughout the time of culture. Furthermore, the immuno-selected populations showed a greater differentiative potential towards adipocytes, osteoblasts and chondrocyte-like cells, compared to PA hASCs. Our data suggest that both CD34+ and L-NGFR+ hASCs can be considered alternative candidates for tissue engineering and regenerative medicine applications. PMID: 19929314 [PubMed - as supplied by publisher] | | | 
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