|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Potential of Human Embryonic Stem Cells in Cartilage Tissue Engineering and Regenerative Medicine. Stem Cell Rev. 2010 Dec 29; Authors: Toh WS, Lee EH, Cao T The current surgical intervention of using autologous chondrocyte implantation (ACI) for cartilage repair is associated with several problems such as donor site morbidity, de-differentiation upon expansion and fibrocartilage repair following transplantation. This has led to exploration of the use of stem cells as a model for chondrogenic differentiation as well as a potential source of chondrogenic cells for cartilage tissue engineering and repair. Embryonic stem cells (ESCs) are advantageous, due to their unlimited self-renewal and pluripotency, thus representing an immortal cell source that could potentially provide an unlimited supply of chondrogenic cells for both cell and tissue-based therapies and replacements. This review aims to present an overview of emerging trends of using ESCs in cartilage tissue engineering and regenerative medicine. In particular, we will be focusing on ESCs as a promising cell source for cartilage regeneration, the various strategie! s and approaches employed in chondrogenic differentiation and tissue engineering, the associated outcomes from animal studies, and the challenges that need to be overcome before clinical application is possible. PMID: 21188652 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Replicative senescence of human bone marrow and umbilical cord derived mesenchymal stem cells and their differentiation to adipocytes and osteoblasts. Mol Biol Rep. 2010 Dec 29; Authors: Cheng H, Qiu L, Ma J, Zhang H, Cheng M, Li W, Zhao X, Liu K Mesenchymal stem cells (MSC) which have self-renewal and multiple differentiation potential in vitro play important roles in regenerative medicine and tissue engineering. However, long-term culture in vitro leads to senescence which results in the growth arrest and reduction of differentiation. In this study, MSC derived from human bone-marrow (BM-MSC) and umbilical cord (UC-MSC) were cultured in vitro lasted to senescence. Senescence and apoptosis detection showed that the senescent cells increased significantly but the increase of apoptosis was not significant in the long term culture. Senescence related genes p16, p21 and p53 increased gradually in BM-MSC. However, p16 and p53 reduced and then increased but with the gradual increase of p21 in UC-MSC. Adipogenic differentiation decreased whereas the propensity for osteogenic differentiation increased in senescent MSC. Real time RT-PCR demonstrated that both C/EBPα and PPARγ decreased in senescent BM-MSC. Howev! er, in UC-MSC, PPARγ decreased but C/EBPα increased in late phase compared to early phase. The study demonstrated p21 was important in the senescence of BM-MSC and UC-MSC. C/EBPα and PPARγ could regulate the balance of adipogenic differentiation in BM-MSC but only PPARγ not C/EBPα was involved in the adipogenic differentiation in UC-MSC. PMID: 21188535 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Vascular guidance: microstructural scaffold patterning for inductive neovascularization. Stem Cells Int. 2010;2011:547247 Authors: Muller D, Chim H, Bader A, Whiteman M, Schantz JT Current tissue engineering techniques are limited by inadequate vascularisation and perfusion of cell-scaffold constructs. Microstructural patterning through biomimetic vascular channels within a polymer scaffold might induce neovascularization, allowing fabrication of large engineered constructs. The network of vascular channels within a frontal-parietal defect in a patient, originating from the anterior branch of the middle meningeal artery, was modeled using computer-aided design (CAD) techniques and subsequently incorporated into polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffolds and implanted into a rat model, with an arteriovenous bundle inserted at the proximal extent of the vascular network. After 3 weeks, scaffolds were elevated as a prefabricated composite tissue-polymer flap and transferred using microsurgical technique. Histological examinat! ion of explanted scaffolds revealed vascular ingrowth along patterned channels, with abundant capillary and connective tissue formation throughout experimental scaffolds, while control scaffolds showed only granulation tissue. All prefabricated constructs transferred as free flaps survived and were viable. We term this concept "vascular guidance," whereby neovascularization is guided through customized channels in a scaffold. Our technique might potentially allow fabrication of much larger tissue-engineered constructs than current technologies allow, as well as allowing tailored construct fabrication with a patient-specific vessel network based on CT scan data and CAD technology. PMID: 21188080 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Interactions of meniscal cells with extracellular matrix molecules: Towards the generation of tissue engineered menisci. Cell Adh Migr. 2011 Mar 1;5(2) Authors: Tan GK, Cooper-White JJ Menisci are one of the most commonly injured parts of the knee. Conventional surgical interventions are often associated with a long-term increased risk of osteoarthritis. Meniscal tissue engineering utilizes natural or synthetic matrices as a scaffold to guide tissue repair or regeneration in three dimensions. Studies have shown that a diverse cellular response can be triggered depending on the composition of the surrounding extracellular matrix (ECM) components. As such, attempts have been made to replace or repair meniscus defects using tissue grafts or reconstituted ECM components prepared from a multitude of tissues. This commentary summarizes the most recent data on the response of meniscal cells to ECM components, both in vivo and in vitro, and focuses on their potential roles in meniscal repair and regeneration. We also discuss our recent investigations into the interactions of meniscal cells and a self assembled biomimetic surface composed of meniscal ECM! molecules. The biological effects conferred by the biomimetic surface, in terms of cell adhesion, proliferation, gene expression profiles and matrix synthesis, were evaluated. Finally, some suggested directions for future research in this field are outlined. PMID: 21187716 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Enhanced Attachment, Growth and Migration of Smooth Muscle Cells on Microcarriers Produced Using a Thermally Induced Phase Separation. Acta Biomater. 2010 Dec 24; Authors: Ahmadi R, Mordan N, Forbes A, Day RM Microcarriers are widely used for the expansion of cells in vitro but also offer an approach for combining cell transplantation and tissue bulking for regenerative medicine in a minimally invasive manner. This could be beneficial in conditions associated with muscle damage or atrophy, such as faecal incontinence, where the use of bulking materials or cell transplantation alone has proven to be ineffective. Microcarriers currently available have not been designed for this purpose and are likely to be suboptimal due to their physical and biochemical properties. The aim of this study was to investigate macroporous microspheres of polylactide-co-glycolide (PLGA), prepared using a thermally induced phase separation (TIPS) technique, for their suitability as cell microcarriers for the transplantation of smooth muscle cells. Cell attachment, growth, and migration were studied and compared with the commercially available porcine gelatin microcarriers (Cultispher-S) in sus! pension culture. Smooth muscle cells attached more rapidly to the PLGA microcarriers, which also significantly enhanced the rate of cell growth compared with Cultispher-S microcarriers. The majority of smooth muscle cells attached to the PLGA microcarriers in suspension culture were able to migrate away over a 15 day period of static culture, unlike Cultispher-S microcarriers which retained the majority of cells. The ability of PLGA microcarriers to enhance cell growth combined with their capacity to release cells at sites of delivery are features that make them ideally suited for use as a cell transplantation delivery device in tissue engineering and regenerative medicine. PMID: 21187173 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Thermoresponsive, in situ crosslinkable hydrogels based on N-isopropylacrylamide: Fabrication, characterization and mesenchymal stem cell encapsulation. Acta Biomater. 2010 Dec 24; Authors: Klouda L, Perkins KR, Watson BM, Hacker MC, Bryant SJ, Raphael RM, Kasper FK, Mikos AG Hydrogels that solidify in response to a dual, physical and chemical, mechanism upon temperature increase were fabricated and characterized. The hydrogels were based on N-isopropylacrylamide, which renders them thermoresponsive, and contained covalently crosslinkable moieties in the macromers. The effects of the macromer end group, namely acrylate or methacrylate, and the fabrication conditions were investigated on the degradative and swelling properties of the hydrogels. The hydrogels exhibited higher swelling below their lower critical solution temperature (LCST). When immersed in cell culture media at physiological temperature, which was above their LCST, hydrogels showed constant swelling and no degradation over eight weeks, with methacrylated hydrogels having higher swelling than their acrylated analogs. In addition, hydrogels immersed in cell culture media under the same conditions showed lower swelling as compared to phosphate buffered saline. The interplay! between chemical crosslinking and thermally induced phase separation affected the swelling characteristics of hydrogels in different media. Mesenchymal stem cells encapsulated in the hydrogels in vitro were viable over three weeks and markers of osteogenic differentiation were detected when the cells were cultured with osteogenic supplements. Hydrogel mineralization in the absence of cells was observed in cell culture medium with the addition of fetal bovine serum and β-glycerol phosphate. The results suggest that these hydrogels may be suitable as carriers for cell delivery in tissue engineering. PMID: 21187170 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Novel nanostructured scaffolds as therapeutic replacement options for rotator cuff disease. J Bone Joint Surg Am. 2010 Dec;92 Suppl 2:170-9 Authors: Taylor ED, Nair LS, Nukavarapu SP, McLaughlin S, Laurencin CT PMID: 21123600 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Future prospect of regenerative medicine into cure of genetic diseases]. Nippon Rinsho. 2010 Aug;68 Suppl 8:71-5 Authors: Okuno H, Kosaki K PMID: 20976887 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. Am J Sports Med. 2010 Sep;38(9):1857-69 Authors: Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J, Josten C, Bader A, Marquass B The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects. PMID: 20508078 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Potential of Human Embryonic Stem Cells in Cartilage Tissue Engineering and Regenerative Medicine. Stem Cell Rev. 2010 Dec 29; Authors: Toh WS, Lee EH, Cao T The current surgical intervention of using autologous chondrocyte implantation (ACI) for cartilage repair is associated with several problems such as donor site morbidity, de-differentiation upon expansion and fibrocartilage repair following transplantation. This has led to exploration of the use of stem cells as a model for chondrogenic differentiation as well as a potential source of chondrogenic cells for cartilage tissue engineering and repair. Embryonic stem cells (ESCs) are advantageous, due to their unlimited self-renewal and pluripotency, thus representing an immortal cell source that could potentially provide an unlimited supply of chondrogenic cells for both cell and tissue-based therapies and replacements. This review aims to present an overview of emerging trends of using ESCs in cartilage tissue engineering and regenerative medicine. In particular, we will be focusing on ESCs as a promising cell source for cartilage regeneration, the various strategie! s and approaches employed in chondrogenic differentiation and tissue engineering, the associated outcomes from animal studies, and the challenges that need to be overcome before clinical application is possible. PMID: 21188652 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | CD16 antigen is a positive marker of peripheral blood-derived early endothelial progenitor cells. Int J Hematol. 2010 Dec 25; Authors: Kimura T, Kohno H, Matsuoka Y, Nakatsuka R, Sasaki Y, Fukuhara S, Sonoda Y PMID: 21188564 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Replicative senescence of human bone marrow and umbilical cord derived mesenchymal stem cells and their differentiation to adipocytes and osteoblasts. Mol Biol Rep. 2010 Dec 29; Authors: Cheng H, Qiu L, Ma J, Zhang H, Cheng M, Li W, Zhao X, Liu K Mesenchymal stem cells (MSC) which have self-renewal and multiple differentiation potential in vitro play important roles in regenerative medicine and tissue engineering. However, long-term culture in vitro leads to senescence which results in the growth arrest and reduction of differentiation. In this study, MSC derived from human bone-marrow (BM-MSC) and umbilical cord (UC-MSC) were cultured in vitro lasted to senescence. Senescence and apoptosis detection showed that the senescent cells increased significantly but the increase of apoptosis was not significant in the long term culture. Senescence related genes p16, p21 and p53 increased gradually in BM-MSC. However, p16 and p53 reduced and then increased but with the gradual increase of p21 in UC-MSC. Adipogenic differentiation decreased whereas the propensity for osteogenic differentiation increased in senescent MSC. Real time RT-PCR demonstrated that both C/EBPα and PPARγ decreased in senescent BM-MSC. Howev! er, in UC-MSC, PPARγ decreased but C/EBPα increased in late phase compared to early phase. The study demonstrated p21 was important in the senescence of BM-MSC and UC-MSC. C/EBPα and PPARγ could regulate the balance of adipogenic differentiation in BM-MSC but only PPARγ not C/EBPα was involved in the adipogenic differentiation in UC-MSC. PMID: 21188535 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The decreases of nephrin and nuclear WT1 in podocytes may cause albuminuria during the experimental sepsis in mice. Biomed Res. 2010;31(6):363-9 Authors: Kato T, Mizuno S, Kamimoto M Sepsis is induced by infectious challenges, and septic organ failure often occurs under local and systemic inflammation. Albuminuria is also evident during sepsis, but little is known about the molecular basis of septic albuminuria. Using lipopolysaccharide (LPS)-treated mice as a sepsis model, we found that the loss of nephrin, a key component for maintaining podocyte slit diaphragm, became evident in accordance with the onset of albuminuria, especially 36 h post-LPS challenge (i.e., albumiuric stage). Likewise, nephrin mRNA levels were decreased to 13% of saline-treated mice. Such a transcriptional suppression of nephrin was associated with the loss of nucleus-localized Wilms tumor-1 (WT1), a transcriptional factor for up-regulating nephrin gene. Thereafter, urinary albumin levels were decreased in mice between 72 and 96 h post-LPS challenge (i.e., recovery-stage). Notably, nuclear localization of WT1 seemed to be normalized, and nephrin mRNA and protein levels ! returned near the basal level 72 h post-LPS challenge. During LPS-mediated sepsis, there was a transient increase in blood interleukin-1β, a suppressor of nephrin production in podocytes. Therefore, down-regulation of nephrin by the loss in nuclear WT1, along with hyper-cytokinemia, may underlie the mechanisms by which albuminuria is induced by infectious stresses. PMID: 21187647 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Enhanced Attachment, Growth and Migration of Smooth Muscle Cells on Microcarriers Produced Using a Thermally Induced Phase Separation. Acta Biomater. 2010 Dec 24; Authors: Ahmadi R, Mordan N, Forbes A, Day RM Microcarriers are widely used for the expansion of cells in vitro but also offer an approach for combining cell transplantation and tissue bulking for regenerative medicine in a minimally invasive manner. This could be beneficial in conditions associated with muscle damage or atrophy, such as faecal incontinence, where the use of bulking materials or cell transplantation alone has proven to be ineffective. Microcarriers currently available have not been designed for this purpose and are likely to be suboptimal due to their physical and biochemical properties. The aim of this study was to investigate macroporous microspheres of polylactide-co-glycolide (PLGA), prepared using a thermally induced phase separation (TIPS) technique, for their suitability as cell microcarriers for the transplantation of smooth muscle cells. Cell attachment, growth, and migration were studied and compared with the commercially available porcine gelatin microcarriers (Cultispher-S) in sus! pension culture. Smooth muscle cells attached more rapidly to the PLGA microcarriers, which also significantly enhanced the rate of cell growth compared with Cultispher-S microcarriers. The majority of smooth muscle cells attached to the PLGA microcarriers in suspension culture were able to migrate away over a 15 day period of static culture, unlike Cultispher-S microcarriers which retained the majority of cells. The ability of PLGA microcarriers to enhance cell growth combined with their capacity to release cells at sites of delivery are features that make them ideally suited for use as a cell transplantation delivery device in tissue engineering and regenerative medicine. PMID: 21187173 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Robust differentiation of fetal hepatocytes from human embryonic stem cells and iPS.] Med Sci (Paris). 2010 Dec;26(12):1061-1066 Authors: Touboul T, Vallier L, Weber A Hepatocyte transplantation is considered as an alternative to organ transplantation in particular for the treatment of liver metabolic diseases. However, due to the difficulties to obtain a large number of hepatocytes, new sources of cells are needed. These cells could be either of hepatic origin (hepatic stem cells) or extrahepatic such as mesenchymal stem cells or pluripotent stem cells (human embryonic stem cells [hESC] or iPS). We developed a new method to differentiate hESCs into fetal hepatocytes. These conditions recapitulate the main liver developmental stages, using fully defined medium devoid of animal products or unknown factors. The differentiated cells express many fetal hepatocytes markers (cytochrome P450 3A7, albumin, alpha-1-antitrypsin, etc.). The cells display specific hepatic functions (ammonia metabolism, excretion of indocyanin green) and are capable to engraft and express hepatic proteins two months after transplantation into newborn uPA x r! ag2gc-/- mouse liver. We have also showed that this approach is transposable to human iPS, and further studies on animal models will allow us to compare the in vivo potential of these two sources of pluripotent cells. Finally, only studies on large animals such as nonhuman primates will validate an eventual clinical application. ‡ PMID: 21187045 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Induced pluripotent stem (iPS) cells and endothelial cell generation: SIRT-ainly a good idea! Atherosclerosis. 2010 Sep;212(1):36-9 Authors: Moura R, Fadini GP, Tjwa M PMID: 20638064 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Injectable materials for the treatment of myocardial infarction and heart failure: the promise of decellularized matrices. J Cardiovasc Transl Res. 2010 Oct;3(5):478-86 Authors: Singelyn JM, Christman KL Cardiovascular disease continues to be the leading cause of death, suggesting that new therapies are needed to treat the progression of heart failure post-myocardial infarction. As cardiac tissue has a limited ability to regenerate itself, experimental biomaterial therapies have focused on the replacement of necrotic cardiomyocytes and repair of the damaged extracellular matrix. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable materials offer the prospective advantage of minimally invasive delivery directly into the myocardium to either replace the damaged extracellular matrix or to act as a scaffold for cell delivery. Cardiac-specific decellularized matrices offer the further advantage of being biomimetic of the native biochemical and structural matrix composition, as well as the potential to be autologous therapies. This review will focus on the requirements of an ideal scaffold for catheter-b! ased delivery as well as highlight the promise of decellularized matrices as injectable materials for cardiac repair. PMID: 20632221 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Axon growth inhibition signals and strategies to treat injuries to the central nervous system]. Tanpakushitsu Kakusan Koso. 2008 Mar;53(4 Suppl):406-10 Authors: Yamashita T PMID: 21089311 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | STEM CELL THERAPY FOR DIGESTIVE TRACT DISEASES: CURRENT STATE AND FUTURE PERSPECTIVES. Stem Cells Dev. 2010 Dec 27; Authors: Trebol J, Georgiev-Hristov T, García-Arranz M, García-Olmo D Diseases of the digestive tract are complex and encompass a broad spectrum of different pathogeneses (inflammatory, ischemic, neoplastic, functional deficit). The digestive tract is not a sterile environment and its organs are composed of tissues with different embryologic origin and different morphologic and functional complexity. As a consequence, the management of these diseases is often challenging. Stem cell therapy has yielded some promising results in preclinical studies and, recently, some approaches have been tested clinically. Indeed, during the last 5 years, the number of clinical trials with stem cells for treatment of digestive tract diseases has increased 10-fold. The most advanced programmes involve liver failure, Crohn´s Disease and fistulous disease and are now in phase III of development. If progress continues and the preliminary results are confirmed, stem cell therapy will become a clinical reality in the near future. In this review we examine! the basic concepts of the stem cell therapy, analyse the potential benefits of stem cells in diseases of the digestive tract and summarise current experience in the field and the future perspectives. PMID: 21187000 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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