|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Role of Altered Signal Transduction in Heterotopic Ossification and Fibrodysplasia Ossificans Progressiva. Curr Osteoporos Rep. 2011 Feb 22; Authors: Shore EM, Kaplan FS Heterotopic ossification is a pathologic condition in which bone tissue is formed outside of the skeleton, within soft tissues of the body. The extraskeletal bone that forms in these disorders is normal; the cellular mechanisms that direct cell fate decisions are dysregulated. Patients with fibrodysplasia ossificans progressiva (FOP), a rare human genetic disorder of extensive and progressive heterotopic ossification, have malformations of normal skeletal elements, identifying the causative gene mutation and its relevant signaling pathways as key regulators of skeletal development and of cell fate decisions by adult stem cells. The discovery that mildly activating mutations in ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, is the cause of FOP has provided opportunities to identify previously unknown functions for this receptor and for BMP signaling and to develop new diagnostic and therapeutic strategies for FOP and other more common forms of heterotopic ossification, as well as tissue engineering applications. PMID: 21340697 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chitosan scaffolds for osteochondral tissue regeneration. J Biomed Mater Res A. 2010 Dec 15;95(4):1132-41 Authors: Abarrategi A, Lópiz-Morales Y, Ramos V, Civantos A, López-Durán L, Marco F, López-Lacomba JL A variety of biomaterials have been introduced as potential substrates for cartilage repair. One such candidate is chitosan, which shares some characteristics with glycosaminoglycan and hyaluronic acid present in articular cartilage. Depending on chitosan source and preparation procedure, variations into its properties can be attained. Thus, the aim of this article is to study and select the most adequate chitosan properties for in vivo osteochondral tissue regeneration. In this work, chitosan molecular weight, deacetylation degree, and calcium content are tested as material variable properties. According to these properties, porous scaffolds were prepared, implanted in rabbit knee osteochondral defects, and evaluated 3 months after surgery. Results show in vitro a considerable influence of the material molecular weight on the scaffold structure. In vivo, different tissue responses were observed depending on the implanted chitosan properties. Some samples showed no material degradation, multiple adverse tissue responses, and no bone/cartilage tissue formation. Other samples showed no adverse responses and bone and cartilage tissue regeneration. The chitosan with intact mineral content (17.9 wt %), lowest molecular weight (11.49 KDa), and lowest deacetylation degree (83%) shows a well structured subchondral bone and noticeable cartilaginous tissue regeneration, being it the best one of those tested for osteochondral defect regeneration. PMID: 20878984 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Long-term stability of cell micropatterns on poly((3-(methacryloylamino)propyl)-dimethyl(3-sulfopropyl)ammonium hydroxide)-patterned silicon oxide surfaces. Biomaterials. 2010 Dec;31(36):9565-74 Authors: Cho WK, Kong B, Park HJ, Kim J, Chegal W, Choi JS, Choi IS In this work, we compared the long-term stability and integrity of cell patterns on newly reported, zwitterionic poly((3-(methacryloylamino)propyl)dimethyl(3-sulfopropyl)ammonium hydroxide) (poly(MPDSAH)) films with those on widely used, poly(poly(ethylene glycol) methyl ether methacrylate) (poly(PEGMEMA)) ones. The micropatterns of both polymers were formed on a silicon oxide surface by a combination of micropattern generation of a photoresist, vapor deposition of a silane-based polymerization initiator, and surface-initiated, atom transfer radical polymerization (SI-ATRP) of each monomer, MPDSAH or PEGMEMA. The successful formation of the silane initiator SAMs, and poly(MPDSAH) and poly(PEGMEMA) micropatterns was confirmed by X-ray photoelectron spectroscopy (XPS) and imaging ellipsometry. Onto each substrate patterned with poly(MPDSAH) or poly(PEGMEMA), NIH 3T3 fibroblast cells were seeded, and the cell micropatterns were generated by the selective adhesion of cells on the cell-adhesive region of the patterned surfaces. The cell pattern formed on the poly(MPDSAH)-patterned surface was observed to have a superior ability of finely maintaining its original, line-shaped structure up to for 20 days, when compared with the cell pattern formed on the poly(PEGMEMA)-patterned surface. In order to verify the relationship between the integrity of the cell micropatterns and the stability of the underlying non-biofouling polymer layers, we also investigated the long-term stability of the polymer films themselves, immersed in the cell culture media, for one month, in the aid of ellipsometry, contact goniometry, and XPS. PMID: 21056465 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Design and Testing of a Pulsatile Conditioning System for Dynamic Endothelialization of Polyphenol-Stabilized Tissue Engineered Heart Valves. Cardiovasc Eng Technol. 2010 Jun;1(2):138-153 Authors: Sierad LN, Simionescu A, Albers C, Chen J, Maivelett J, Tedder ME, Liao J, Simionescu DT Heart valve tissue engineering requires biocompatible and hemocompatible scaffolds that undergo remodeling and repopulation, but that also withstand harsh mechanical forces immediately following implantation. We hypothesized that reversibly stabilized acellular porcine valves, seeded with endothelial cells and conditioned in pulsatile bioreactors would pave the way for next generations of tissue engineered heart valves (TEHVs). A novel valve conditioning system was first designed, manufactured and tested to adequately assess TEHVs. The bioreactor created proper closing and opening of valves and allowed for multiple mounting methods in sterile conditions. Porcine aortic heart valve roots were decellularized by chemical extractions and treated with penta-galloyl glucose (PGG) for stabilization. Properties of the novel scaffolds were evaluated by testing resistance to collagenase and elastase, biaxial mechanical analysis, and thermal denaturation profiles. Porcine aortic endothelial cells were seeded onto the leaflets and whole aortic roots were mounted within the dynamic pulsatile heart valve bioreactor system under physiologic pulmonary valve pressures and analyzed after 17 days for cell viability, morphology, and metabolic activity. Our tissue preparation methods effectively removed cells, including the potent α-Gal antigen, while leaving a well preserved extra-cellular matrix scaffold with adequate mechanical properties. PGG enhanced stabilization of extracellular matrix components but also showed the ability to be reversible. Engineered valve scaffolds encouraged attachment and survival of endothelial cells for extended periods and showed signs of widespread cell coverage after conditioning. Our novel approach shows promise toward development of sturdy and durable TEHVs capable of remodeling and cellular repopulation. PMID: 21340043 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology. Tissue Eng Part B Rev. 2011 Feb 21; Authors: Bodle JC, Hanson AD, Loboa E This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID: 21338267 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerated silk fibroin scaffold and infrapatellar adipose stromal vascular fraction as feeder layer: a new product for cartilage advanced therapy. Tissue Eng Part A. 2011 Feb 21; Authors: Chlapanidas T, Faragò S, Mingotto F, Crovato F, Tosca MC, Antonioli B, Bucco M, Lucconi G, Scalise A, Vigo D, Faustini M, Marazzi M, Torre ML Articular cartilage has limited repair and regeneration potential and the scarcity of treatment modalities has motivated attempts to engineer cartilage tissue constructs. The use of chondrocytes in cartilage tissue engineering has been restricted by the limited availability of these cells, their intrinsic tendency to lose their phenotype during the expansion, as well as the difficulties during the first cell adhesion to the scaffold. Aim of this work was to evaluate the intrarticular adipose stromal vascular fraction attachment on silk fibroin scaffold in order to promote chondrocytes adhesion and proliferation. Physicochemical characterization has demonstrated that 3D-organized silk fibroin scaffold is an ideal biopolymer for cartilage tissue engineering; it allows cell attachment, scaffold colonization and physically cell holding in the area that must be repaired; the use of adipose-derived stem cells is a promising strategy to promote adhesion and proliferation of chondrocytes to the scaffold as an autologous human feeder layer. PMID: 21338265 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes. Biomaterials. 2010 Dec;31(36):9406-14 Authors: Liu X, Sun H, Yan D, Zhang L, Lv X, Liu T, Zhang W, Liu W, Cao Y, Zhou G In vivo niche plays an important role in determining the fate of exogenously implanted stem cells. Due to the lack of a proper chondrogenic niche, stable ectopic chondrogenesis of mesenchymal stem cells (MSCs) in subcutaneous environments remains a great challenge. The clinical application of MSC-regenerated cartilage in repairing defects in subcutaneous cartilage such as nasal or auricular cartilage is thus severely limited. The creation of a chondrogenic niche in subcutaneous environments is the key to solving this problem. The current study demonstrates that bone marrow stromal cells (BMSCs) could form cartilage-like tissue in a subcutaneous environment when co-transplanted with articular chondrocytes, indicating that chondrocytes could create a chondrogenic niche to direct chondrogenesis of BMSCs. Then, a series of in vitro co-culture models revealed that it was the secretion of soluble factors by chondrocytes but not cell-cell contact that provided the chondrogenic signals. The subsequent studies further demonstrated that multiple factors currently used for chondroinduction (including TGF-β1, IGF-1 and BMP-2) were present in the supernatant of chondrocyte-engineered constructs. Furthermore, all of these factors were required for initiating chondrogenic differentiation and fulfilled their roles in a coordinated way. These results suggest that paracrine signaling of soluble chondrogenic factors provided by chondrocytes was an important mechanism in directing the in vivo ectopic chondrogenesis of BMSCs. The multiple co-culture systems established in this study provide new methods for directing committed differentiation of stem cells as well as new in vitro models for studying differentiation mechanism of stem cells determined by a tissue-specific niche. PMID: 21056466 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells. Biomaterials. 2010 Dec;31(36):9452-61 Authors: Wang L, Fan H, Zhang ZY, Lou AJ, Pei GX, Jiang S, Mu TW, Qin JJ, Chen SY, Jin D Although vascularized tissue-engineered bone grafts (TEBG) have been generated ectopically in several studies, the use of prevascularized TEBG for segmental bone defect repair are rarely reported. In current study, we investigated the efficacy of prevascularized TEBG for segmental defect repair. The segmental defects of 15 mm in length were created in the femurs of rabbits bilaterally. In treatment group, the osteotomy site of femur was implanted with prevascularized TEBG, which is generated by seeding mesenchymal stem cells (MSCs) into β-TCP scaffold, and prevascularization with the insertion of femoral vascular bundle into the side groove of scaffold; whereas in the control group, only MSC mediated scaffolds (TEBG) were implanted. The new bone formation and vascularization were investigated and furthermore, the expression of endogenous vascular endothelial growth factor (VEGF) which might express during defect healing was evaluated, as well. At 4, 8, and 12 weeks postoperatively, the treatment of prevascularized TEBG led to significantly higher volume of regenerated bone and larger amount of capillary infiltration compared to non-vascularized TEBG. The expression of VEGF in mRNA and protein levels increased with implantation time and peaked at 4 weeks postoperatively, followed by a slow decrease, however, treatment group expressed a significant higher level of VEGF than control group throughout the whole study. In conclusion, this study demonstrated that prevascularized TEBG by insertion of vascular bundle could significantly promote the new bone regeneration and vascularization compared to non-vascularized TEBG, which could be partially explained by the up-regulated expression of VEGF. PMID: 20869769 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Influence of stress on extracellular matrix and integrin biology. Oncogene. 2011 Feb 21; Authors: Jean C, Gravelle P, Fournie JJ, Laurent G Dynamic interactions between cells and extracellular matrix (ECM) through integrins influence most cellular functions. Normal cells, but even more, tumor cells are subjected to different forms of stress, including ischemia, radical oxygen species production, starvation, mechanical stress or genotoxic insults due to anti-cancer drugs or irradiation. In these situations, an adaptative cellular response occurs, integrating a complex network of intracellular signaling modules, which, depending on stress intensity, may result to either damage repair followed by complete restitution of cellular functions, or programmed cell death. Because of its implication in oncogenesis and anti-cancer therapy, cellular stress response has been thoroughly investigated. However, most of these studies have been performed in the context of isolated cells without taking into consideration that most cells are part of the tissue within which they interact with ECM through integrin. Few studies have described the influence of stress on cell-to-ECM interaction. However, one can speculate that, in these conditions, cells could functionally interact with protein microenvironment either to create positive interactions to survive (for example by facilitating protective pathways) or negative interaction to die (for example by facilitating detachment). In this review, we summarize the knowledge relative to the influence of different stress modalities on ECM remodeling, integrin expression and/or function modifications, and possible functional consequences, independently from the cellular model as these findings came from a large variety of cells (mesenchymal, endothelial, muscular, epithelial and glandular) and fields of application (cancer, vascular biology and tissue engineering). Most studies support the general notion that non-lethal stress favors ECM stiffness, integrin activation and enhanced survival. This field opens large perspectives not only in tumor biology but also in anti-cancer therapy by targeting one or several steps of the integrin-mediated signaling pathway, including integrin ligation, or activation of integrin-linked enzymes or integrin adaptors.Oncogene advance online publication, 21 February 2011; doi:10.1038/onc.2011.27. PMID: 21339741 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Decellularization and recellularization of whole livers. J Vis Exp. 2011;(48): Authors: Uygun BE, Price G, Saedi N, Izamis ML, Berendsen T, Yarmush M, Uygun K The liver is a complex organ which requires constant perfusion for delivery of nutrients and oxygen and removal of waste in order to survive(1). Efforts to recreate or mimic the liver microstructure with grounds up approach using tissue engineering and microfabrication techniques have not been successful so far due to this design challenge. In addition, synthetic biomaterials used to create scaffolds for liver tissue engineering applications have been limited in inducing tissue regeneration and repair in large part due to the lack of specific cell binding motifs that would induce the proper cell functions(2). Decellularized native tissues such blood vessels(3)and skin(4)on the other hand have found many applications in tissue engineering, and have provided a practical solution to some of the challenges. The advantage of decellularized native matrix is that it retains, to an extent, the original composition, and the microstructure, hence enhancing cell attachment and reorganization(5). In this work we describe the methods to perform perfusion-decellularization of the liver, such that an intact liver bioscaffold that retains the structure of major blood vessels is obtained. Further, we describe methods to recellularize these bioscaffolds with adult primary hepatocytes, creating a liver graft that is functional in vitro, and has the vessel access necessary for transplantation in vivo. PMID: 21339718 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The discrimination of type I and type II collagen and the label-free imaging of engineered cartilage tissue. Biomaterials. 2010 Dec;31(36):9415-21 Authors: Su PJ, Chen WL, Li TH, Chou CK, Chen TH, Ho YY, Huang CH, Chang SJ, Huang YY, Lee HS, Dong CY Using excitation polarization-resolved second harmonic generation (SHG) microscopy, we measured SHG intensity as a function of the excitation polarization angle for type I and type II collagens. We determined the second order susceptibility (χ((2))) tensor ratios of type I and II collagens at each pixel, and displayed the results as images. We found that the χ((2)) tensor ratios can be used to distinguish the two types of collagen. In particular, we obtained χ(zzz)/χ(zxx) = 1.40 ± 0.04 and χ(xzx)/χ(zxx) = 0.53 ± 0.10 for type I collagen from rat tail tendon, and χ(zzz)/χ(zxx) = 1.14 ± 0.09 and χ(xzx)/χ(zxx) = 0.29 ± 0.11 for type II collagen from rat trachea cartilage. We also applied this methodology on the label-free imaging of engineered cartilage tissue which produces type I and II collagen simultaneously. By displaying the χ((2)) tensor ratios in the image format, the variation in the χ((2)) tensor ratios can be used as a contrast mechanism for distinguishing type I and II collagens. PMID: 20875682 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose Derived Stem Cells in Functional Bone Tissue Engineering: Lessons from Bone Mechanobiology. Tissue Eng Part B Rev. 2011 Feb 21; Authors: Bodle JC, Hanson AD, Loboa E This review aims to highlight the current and significant work in the use of adipose-derived stem cells (ASC) in functional bone tissue engineering framed through the bone mechanobiology perspective. Over a century of work on the principles of bone mechanosensitivity is now being applied to our understanding of bone development. We are just beginning to harness that potential using stem cells in bone tissue engineering. ASC are the primary focus of this review due to their abundance and relative ease of accessibility for autologous procedures. This article outlines the current knowledge base in bone mechanobiology to investigate how the knowledge from this area has been applied to the various stem cell-based approaches to engineering bone tissue constructs. Specific emphasis is placed on the use of human ASC for this application. PMID: 21338267 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Emerging therapeutic approaches for multipotent mesenchymal stromal cells. Curr Opin Hematol. 2010 Nov;17(6):505-13 Authors: Caimi PF, Reese J, Lee Z, Lazarus HM Multipotent mesenchymal stromal cells (MSCs) are rare cells resident in bone marrow and other organs capable of differentiating into mesodermal lineage tissues. MSCs possess immunomodulatory properties and have extensive capacity for ex-vivo expansion. Early clinical studies demonstrated safety and feasibility of infusing autologous MSCs and suggested a role in enhancing engraftment after hematopoietic cell transplant (HCT). Subsequent pilot studies using allogeneic MSCs showed safety but presented contradictory results regarding efficacy in treating graft-versus-host disease (GVHD). PMID: 20729733 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Derivation and characterization of human embryonic stem cell lines from the Chinese population. J Genet Genomics. 2011 Jan;38(1):13-20 Authors: Wu Z, Li H, Rao L, He L, Bao L, Liao J, Cui C, Zuo Z, Li Q, Dai H, Qian L, Tian Q, Xiao L, Tan X Human embryonic stem cells (hESCs) can self-renew indefinitely and differentiate into all cell types in the human body. Therefore, they are valuable in regenerative medicine, human developmental biology and drug discovery. A number of hESC lines have been derived from the Chinese population, but limited of them are available for research purposes. Here we report the derivation and characterization of two hESC lines derived from human blastocysts of Chinese origin. These hESCs express alkaline phosphatase and hESC-specific markers, including Oct4, Nanog, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. They also have high levels of telomerase activity and normal karyotypes. These cells can form embryoid body in vitro and can be differentiated into all three germ layers in vivo by teratoma formation. The newly established hESCs will be distributed for research purposes. The availability of hESC lines from the Chinese population will facilitate studies on the differences in hESCs from different ethnic groups. PMID: 21338948 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Hematopoietic Stem Cell Homing to Injured Tissues. Stem Cell Rev. 2011 Feb 22; Authors: Kavanagh DP, Kalia N The use of stem cells is considered a promising therapy for tissue regeneration and repair, particularly for tissues injured through degeneration, ischemia and inflammation. Bone marrow (BM)-derived haematopoietic stem cells (HSCs) are rare populations of multipotent stem cells that have been identified as promising potential candidates for treating a broad range of conditions. Although research into the use of stem cells for regenerative medicine is on a steep upward slope, clinical success has not been as forthcoming. This has been primarily attributed to a lack of information on the basic biology of stem cells, which remains insufficient to justify clinical studies. In particular, while our knowledge on the molecular adhesive mechanisms and local environmental factors governing stem cell homing to BM is detailed, our understanding of the mechanisms utilized at injured sites is very limited. For instance, it is unclear whether mechanisms used at injured sites are location specific or whether this recruitment can be modulated for therapeutic purposes. In addition, it has recently been suggested that platelets may play an important role in stem cell recruitment to sites of injury. A better understanding of the mechanisms used by stem cells during tissue homing would allow us to develop strategies to improve recruitment of these rare cells. This review will focus on the status of our current understanding of stem cell homing to injured tissues, the role of platelets and directions for the future. PMID: 21340505 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. Dev Biol. 2011 Feb 1;350(1):112-26 Authors: El-Hashash AH, Al Alam D, Turcatel G, Bellusci S, Warburton D The proper level of proliferation and differentiation along the proximodistal axis is crucial for lung organogenesis. Elucidation of the factors that control these processes will therefore provide important insights into embryonic lung development and regeneration. Eya1 is a transcription factor/protein phosphatase that regulates cell lineage specification and proliferation. Yet its functions during lung development are unknown. In this paper we show that Eya1(-/-) lungs are severely hypoplastic with reduced epithelial branching and increased mesenchymal cellularity. Eya1 is expressed at the distal epithelial tips of branching tubules as well as in the surrounding distal mesenchyme. Eya1(-/-) lung epithelial cells show loss of progenitor cell markers with increased expression of differentiation markers and cell cycle exit. In addition, Eya1(-/-) embryos and newborn mice exhibit severe defects in the smooth muscle component of the bronchi and major pulmonary vessels with decreased Fgf10 expression. These defects lead to rupture of the major vessels and hemorrhage into the lungs after birth. Treatment of Eya1(-/-) epithelial explants in culture with recombinant Fgf10 stimulates epithelial branching. Since Shh expression and activity are abnormally increased in Eya1(-/-) lungs, we tested whether genetically lowering Shh activity could rescue the Eya1(-/-) lung phenotype. Indeed, genetic reduction of Shh partially rescues Eya1(-/-) lung defects while restoring Fgf10 expression. This study provides the first evidence that Eya1 regulates Shh signaling in embryonic lung, thus ensuring the proper level of proliferation and differentiation along the proximodistal axis of epithelial, mesenchymal and endothelial cells. These findings uncover novel functions for Eya1 as a critical upstream coordinator of Shh-Fgf10 signaling during embryonic lung development. We conclude, therefore, that Eya1 function is critical for proper coordination of lung epithelial, mesenchymal and vascular development. PMID: 21129374 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Methods for making induced pluripotent stem cells: reprogramming à la carte. Nat Rev Genet. 2011 Feb 22; Authors: González F, Boué S, Belmonte JC Pluripotent stem-cell lines can be obtained through the reprogramming of somatic cells from different tissues and species by ectopic expression of defined factors. In theory, these cells - known as induced pluripotent stem cells (iPSCs) - are suitable for various purposes, including disease modelling, autologous cell therapy, drug or toxicity screening and basic research. Recent methodological improvements are increasing the ease and efficiency of reprogramming, and reducing the genomic modifications required to complete the process. However, depending on the downstream applications, certain technologies have advantages over others. Here, we provide a comprehensive overview of the existing reprogramming approaches with the aim of providing readers with a better understanding of the reprogramming process and a basis for selecting the most suitable method for basic or clinical applications. PMID: 21339765 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human amniotic membrane as an alternative source of stem cells for regenerative medicine. Differentiation. 2011 Feb 19; Authors: Díaz-Prado S, Muiños-López E, Hermida-Gómez T, Cicione C, Rendal-Vázquez ME, Fuentes-Boquete I, de Toro FJ, Blanco FJ The human amniotic membrane (HAM) is a highly abundant and readily available tissue. This amniotic tissue has considerable advantageous characteristics to be considered as an attractive material in the field of regenerative medicine. It has low immunogenicity, anti-inflammatory properties and their cells can be isolated without the sacrifice of human embryos. Since it is discarded post-partum it may be useful for regenerative medicine and cell therapy. Amniotic membranes have already been used extensively as biologic dressings in ophthalmic, abdominal and plastic surgery. HAM contains two cell types, from different embryological origins, which display some characteristic properties of stem cells. Human amnion epithelial cells (hAECs) are derived from the embryonic ectoderm, while human amnion mesenchymal stromal cells (hAMSCs) are derived from the embryonic mesoderm. Both populations have similar immunophenotype and multipotential for in vitro differentiation into the major mesodermal lineages, however they differ in cell yield. Therefore, HAM has been proposed as a good candidate to be used in cell therapy or regenerative medicine to treat damaged or diseased tissues. PMID: 21339039 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex. Neuron. 2011 Feb 24;69(4):763-79 Authors: Lodato S, Rouaux C, Quast KB, Jantrachotechatchawan C, Studer M, Hensch TK, Arlotta P In the mammalian cerebral cortex, the developmental events governing the integration of excitatory projection neurons and inhibitory interneurons into balanced local circuitry are poorly understood. We report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons. We find that in Fezf2(-/-) cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons and altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birthdate, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry. PMID: 21338885 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Translational systems biology of inflammation: potential applications to personalized medicine. Per Med. 2010 Sep 1;7(5):549-559 Authors: Mi Q, Li NY, Ziraldo C, Ghuma A, Mikheev M, Squires R, Okonkwo DO, Verdolini-Abbott K, Constantine G, An G, Vodovotz Y A central goal of industrialized nations is to provide personalized, preemptive and predictive medicine, while maintaining healthcare costs at a minimum. To do so, we must confront and gain an understanding of inflammation, a complex, nonlinear process central to many diseases that affect both industrialized and developing nations. Herein, we describe the work aimed at creating a rational, engineering-oriented and evidence-based synthesis of inflammation geared towards rapid clinical application. This comprehensive approach, which we call 'Translational Systems Biology', to date has been utilized for in silico studies of sepsis, trauma/hemorrhage/traumatic brain injury, acute liver failure and wound healing. This framework has now allowed us to suggest how to modulate acute inflammation in a rational and individually optimized fashion using engineering principles applied to a biohybrid device. We suggest that we are on the cusp of fulfilling the promise of in silico modeling for personalized medicine for inflammatory disease. PMID: 21339856 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
No comments:
Post a Comment