|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Chemokines in mesenchymal stem cell therapy for bone repair: a novel concept of recruiting mesenchymal stem cells and the possible cell sources. Mod Rheumatol. 2010 Sep 10; Authors: Ito H Skeletal injury is one of the most prevalent clinical problems that jeopardize the activities of daily life, especially in our aging society. Mesenchymal stem cells (MSCs) play pivotal roles in regenerating bones after bone injury. MSCs come from the surrounding tissues and/or circulation. Cell sources may be the bone marrow, periosteum, vessel walls, muscle, circulation, and elsewhere, and the migration of MSCs is necessary for bone healing. The mechanism(s) of recruitment and crucial molecules for cell migration are still unclear, but chemokines and their receptors seem to play critical roles. The induction of MSC recruitment from surrounding tissues or from the circulation can be a helpful modality to induce or to support cell-based therapy for bone regeneration. PMID: 20830500 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Transvalvular intramyocardial bone marrow stem cell transplantation in combination with videoscopic mitral valve repair. Interact Cardiovasc Thorac Surg. 2010 Sep 9; Authors: Donndorf P, Kaminski A, Steinhoff G, Liebold A In the last years both minimally-invasive therapy approaches as well as intramyocardial cell therapy have entered clinical practice in cardiac surgery. Stem cell therapy has been combined in most cases with coronary artery bypass grafting (CABG) for chronic ischemic heart disease. Here, we report the first case of a patient with ischemic mitral regurgitation treated by videoscopic, transvalvular, intramyocardial bone marrow stem cell injection, while undergoing minimally-invasive mitral valve repair. Keywords: Minimally-invasive surgery; Mitral valve; Stem cells. PMID: 20829387 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Optimizing Stem Cell Function for the Treatment of Ischemic Heart Disease. J Surg Res. 2010 Jun 16; Authors: Herrmann JL, Abarbanell AM, Weil BR, Manukyan MC, Poynter JA, Brewster BJ, Wang Y, Meldrum DR BACKGROUND: Stem cell-based therapies for myocardial ischemia have demonstrated promising early clinical results, but their benefits have been limited in duration due to impaired donor cell engraftment and function. Several strategies have emerged for enhancing stem cell function prior to their therapeutic use particularly with regard to stem cell homing, paracrine function, and survival. This review discusses current understandings of stem cell-mediated cardioprotection as well as methods of enhancing post-transplantation stem cell function and survival through hypoxic preconditioning, genetic manipulation, and pharmacologic pretreatment. MATERIALS AND METHODS: A literature search was performed using the MEDLINE and PubMed databases using the keywords "stem cell therapy," "myocardial ischemia," "hypoxic preconditioning," "paracrine function," and "stem cell pretreatment." Studies published in English since January 1990 were selected. In addition, studies were identified from references cited in publications found using the search terms. RESULTS: All included studies utilized animal studies and/or in vitro techniques. Stem cell modifications generally targeted stem cell homing (SDF-1, CXCR4), paracrine function (VEGF, angiogenin, Ang-1, HGF, IL-18 binding protein, TNFR1/2), or survival (Akt, Bcl-2, Hsp20, HO-1, FGF-2). However, individual modifications commonly exhibited pleiotropic effects involving some or all of these general categories. CONCLUSION: These strategies for optimizing stem cell-mediated cardioprotection present unique potential sets of advantages and disadvantages for clinical application. Additional questions remain including those that are most efficacious in terms of magnitude and duration of benefit as well as whether combinations may yield greater benefits in both the preclinical and clinical settings. PMID: 20828719 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Matrix remodeling stem cell recruitment: A novel in vitro model for homing of human bone marrow stromal cells to the site of injury shows crucial role of extracellular collagen matrix. Matrix Biol. 2010 Sep 6; Authors: Mauney J, Olsen BR, Volloch V The goal of the present study was to devise an in vitro model suitable for investigations of the homing of mesenchymal stem cells to sites of injury. Such a model was designed on the basis of a "transwell"assay, with an insert seeded with human bone marrow stromal cells and a well with a desired cell type. To mimic physiological environment and to simulate "injury", cells in a well were maintained not only on tissue culture plastic but also on collagens I and IV, major matrix components in musculoskeletal and adipose tissues respectively, and subjected to a severe thermal stress. The results obtained showed a massive translocation of bone marrow stromal cells through the inserts' membrane toward the "injury" site. Unexpectedly, it emerged that collagen matrix is essential in producing such a migration. The results obtained suggest that upon injury cells secrete a substance which interacts with collagen matrix to produce a homing agent. The substance in question appears to be a protease and its interaction with the collagen matrix a digestion into fragments shown to be chemotactic. Both AEBSF, an inhibitor of serine proteases, and leupeptin, an inhibitor of cysteine proteases as well as of trypsin-like serine proteases, but not the broad spectrum MMP inhibitor marimastat, significantly inhibit the observed homing effect and this inhibition is not due to cytotoxicity. Moreover, immunoprecipitation of HTRA1, a trypsin-like serine protease known to be secreted by cells differentiating into all three major mesenchymal lineages and by stressed cells in general and shown to degrade a number of matrix proteins including collagen, significantly diminished the homing effect. The data suggest that this protease is a major contributor to the observed chemotaxis of bone marrow stromal cells. The present study indicates that collagen fragments can mediate the migration of bone marrow stromal cells. The results also suggest that, at least in musculoskeletal and in adipose tissues, matrix remodeling occurrences, usually closely associated with tissue remodeling, should also be regarded as potential stem cells recruitment events. PMID: 20828613 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose Derived Stromal Cells Autologous Transplantation Ameliorate Pulmonary Arterial Hypertension Induced by Shunt Flow in Rat Models. Stem Cells Dev. 2010 Sep 9; Authors: Liu K, Liu R, Cao G, Sun H, Wang X, Wu S Abstract Background---Hyperkinetic pulmonary arterial hypertension (PAH) severely influences the success of operation for congenital heart disease and deteriorates the prognosis of disease. Adipose-derived stromal cell (ADSC) is a good alternative multipotent stem cell for regeneration medicine. Method and results--- PAH rat models were established by arteriovenous shunt and ADSCs were isolated, cultured and labeled in vitro. Twelve weeks after shunt operation, rats received injection of 5×107 ADSCs. Two weeks after transplantation, hemodynamic abnormality induced by the shunt flow and the hypertrophy of right ventricle were reversed, and it was confirmed by echocardiography examination and invasive measurement. The PAH rats receiving cell transplantation demonstrated the decreased remodeling of small arteries in the lung; immunohistochemistry analysis showed the augmented expression of hepatocyte growth factor (HGF) and the increased number of pulmonary small arteries. Western Blot and Real-time RT-PCR indicated the protein and mRNA levels of HGF and eNOS increased respectively in lung after cell transplantation. Conclusions---Our results suggested that ADSCs transplantation can ameliorate PAH induced by shunt flow through enhancing the expression of HGF and subsequently promote angiogenesis in the injured lung tissue. PMID: 20828291 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Stem cells from fatty tissue : A new resource for regenerative medicine?] Chirurg. 2010 Sep;81(9):826-32 Authors: Kuhbier JW, Weyand B, Sorg H, Radtke C, Vogt PM, Reimers K While stem cells derived from the bone marrow are well-known in clinical medicine, fatty tissue as a source of mesenchymal stem cells is still the subject of recent research. However, adipose-derived stem cells (ASC) are not only harvested less invasively, i.e. via minimally invasive liposuction, but also yield higher numbers of multipotent stem cells.Due to cell-cell interactions and also because of the very favorable secretion profile of growth factors and cytokines ASCs displayed an extraordinary regenerative potential in recent preclinical and clinical applications and achieved a significantly better healing in ischemic muscle, heart, and brain insults and in impaired wound healing. ASCs enhanced regeneration in skeletal tissues such as cartilage or bone. They also revealed immunomodulatory effects and improved the clinical status in immunological diseases.In conclusion ASCs are comparable to bone marrow-derived stem cells concerning possible applications in clinical medicine. PMID: 20830547 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells as therapeutics and vehicles for gene and drug delivery. Adv Drug Deliv Rev. 2010 Sep 6; Authors: Porada CD, Almeida-Porada G Mesenchymal stem cells (MSCs) possess a set of several fairly unique properties which make them ideally suited both for cellular therapies/regenerative medicine, and as vehicles for gene and drug delivery. These include: 1) relative ease of isolation; 2) the ability to differentiate into a wide variety of seemingly functional cell types of both mesenchymal and non-mesenchymal origin; 3) the ability to be extensively expanded in culture without a loss of differentiative capacity; 4) they are not only hypoimmunogenic, but they produce immunosuppression upon transplantation; 5) their pronounced anti-inflammatory properties; and 6) their ability to home to damaged tissues, tumors, and metastases following in vivo administration. In this review, we summarize the latest research in the use of mesenchymal stem cells in regenerative medicine, as immunomodulatory/anti-inflammatory agents, and as vehicles for transferring both therapeutic genes in genetic disease and genes designed to destroy malignant cells. PMID: 20828588 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Introduction to Series on Mesenchymal Stromal (Stem) Cells-MSCs. Hum Gene Ther. 2010 Sep;21(9):1037-8 Authors: O'Brien T, Barry F PMID: 20828294 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Simulated microgravity maintains the undifferentiated state and enhances the neural repair potential of bone marrow stromal cells. Stem Cells Dev. 2010 Sep 9; Authors: Yuge L, Sasaki A, Kawahara Y, Wu S, Matsumoto M, Manabe T, Kajiume T, Takeda M, Magaki T, Takahashi T, Kurisu K, Matsumoto M Recently, regenerative medicine with bone marrow stromal cells (BMSCs) has gained significant attention for the treatment of central nervous system diseases. Here, we investigated the activity of BMSCs under simulated microgravity conditions. Mouse BMSCs (mBMSCs) were isolated from C57BL/6 mice and harvested in 1G condition. Subjects were divided into four groups, cultured in 3D-clinostat (group CL) and 1G condition (group C) under growth medium and neural differentiation medium. After 7 days of culture, the mBMSCs were used for morphological analysis, RT-PCR, immunostaining analysis, and grafting. Neural-induced mBMSCs cultured under 1G conditions exhibited neural differentiation, whereas those cultured under simulated microgravity did not. Moreover, under simulated microgravity conditions, mBMSCs could be cultured in an undifferentiated state. Next, we intravenously injected cells into a mouse model of cerebral contusion. Graft mBMSCs cultured under simulated microgravity exhibited greater survival in the damaged region, and the motor function of the grafted mice improved significantly. mBMSCs cultured under simulated microgravity expressed CXCR4 on their cell membrane. Our study indicates that culturing cells under simulated microgravity enhances their survival rate by maintaining an undifferentiated state of cells, making this a potentially attractive method for culturing donor cells to be used in grafting. PMID: 20828292 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Investigation of the potential of polymer therapeutics in corneal re-epithelialisation. Br J Ophthalmol. 2010 Sep 9; Authors: Hardwicke J, Song B, Moseley R, Thomas DW In this study, the first use of a bioresponsive polymer therapeutic agent in the promotion of corneal re-epithelialisation after injury in an ex vivo whole-eye organ culture model was described. A polymer-protein conjugate consisting of dextrin and recombinant human epidermal growth factor was synthesised and applied as a single dose to a 2 mm ex vivo corneal ulcer, in culture. Enhanced wound healing was observed in response to dextrin-recombinant human epidermal growth factor, when exposed to α-amylase, compared with controls. This highlights the potential for polymer therapeutics to provide a platform for bioresponsive drug/protein delivery in the field of ophthalmology. PMID: 20829315 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The relationship between collagen scaffold cross-linking agents and neutrophils in the foreign body reaction. Biomaterials. 2010 Sep 7; Authors: Ye Q, Harmsen MC, van Luyn MJ, Bank RA In order to get more insight into the role of neutrophils on the micro-environment and consequently on macrophages in the foreign body reaction in mice, we investigated the fate of the two differently cross-linked dermal sheep collagen disks (glutaraldehyde = GDSC, hexamethylenediisocyanate = HDSC) in mice implanted in one anatomical location, namely subcutaneously. In GDSC massive infiltration of neutrophils is seen at day 2 and day 21, whereas in HDSC only minor infiltration is seen at day 2. The presence of neutrophils coincided with high levels of IFN-γ, a cytokine that activates macrophages. Major differences were seen in degradation rate of the two disks: GDSC was almost completely degraded after 28 days, whereas HDSC remained intact. Degradation of GDSC occurred through collagenolytic activity and phagocytosis by macrophages. Phagocytosis was observed at day 2 and day 21. IL-13 was only observed in HDSC, and this resulted in the presence of giant cells in HDSC. These giant cells produced IL-10, that promoted TIMP-1 expression and that inhibits collagenolytic and phagocytic activity. We conclude that the function of macrophages in mice is largely influenced by differences in micro-environment induced by GDSC and HDSC and that the presence/absence of neutrophils play a major role in the shaping of this micro-environment. PMID: 20828809 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Interface-directed self-assembly of cell-laden microgels. Small. 2010 Apr 23;6(8):937-44 Authors: Zamanian B, Masaeli M, Nichol JW, Khabiry M, Hancock MJ, Bae H, Khademhosseini A Cell-laden hydrogels show great promise for creating engineered tissues. However, a major shortcoming with these systems has been the inability to fabricate structures with controlled micrometer-scale features on a biologically relevant length scale. In this Full Paper, a rapid method is demonstrated for creating centimeter-scale, cell-laden hydrogels through the assembly of shape-controlled microgels or a liquid-air interface. Cell-laden microgels of specific shapes are randomly placed on the surface of a high-density, hydrophobic solution, induced to aggregate and then crosslinked into macroscale tissue-like structures. The resulting assemblies are cell-laden hydrogel sheets consisting of tightly packed, ordered microgel units. In addition, a hierarchical approach creates complex multigel building blocks, which are then assembled into tissues with precise spatial control over the cell distribution. The results demonstrate that forces at an air-liquid interface can be used to self-assemble spatially controllable, cocultured tissue-like structures. PMID: 20358531 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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