|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Northwestern this afternoon confirmed that it is the first site to be ready to accept candidates for hESC clinical trials with Geron, Inc., of Menlo Park, Ca. The Illinois organization is also the lead site for the unprecedented trial.
Northwestern's role surfaced during the weekend in a case involving a severely injured California jockey. See here and here.
Here is Northwestern's press | | | | | | | | | | | | | | | | | | | | | | | | The complexities of finding candidates for clinical trials as ground-breaking as the hESC effort by Geron were touched upon indirectly in news coverage of the case of jockey Michael Martinez.
This morning the San Francisco Chronicle noted that the state workers' compensation department played a negative role in the matter. Earlier, the Daily Racing Form reported that Highland Hospital in | | | | | | | | | | | | | | | | | | | | | | | | | Stromal stem cells from adipose tissue and bone marrow of age matched female donors display distinct immunophenotypic profiles. J Cell Physiol. 2010 Sep 20; Authors: Pachón-Peña G, Yu G, Tucker A, Wu X, Vendrell J, Bunnell B, Gimble J Adipose tissue is composed of lipid-filled mature adipocytes and a heterogeneous stromal vascular fraction (SVF) population of cells. Similarly, the bone marrow (BM) is composed of multiple cell types including adipocytes, hematopoietic, osteoprogenitor, and stromal cells necessary to support hematopoiesis. Both adipose and BM contain a population of mesenchymal stromal/stem cells with the potential to differentiate into multiple lineages, including adipogenic, chondrogenic, and myogenic cells, depending on the culture conditions. In this study we have shown that human adipose derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) populations display a common expression profile for many surface antigens, including CD29, CD49c, CD147, CD166, and HLA-abc. Nevertheless, significant differences were noted in the expression of CD34 and its related protein, PODXL, CD36, CD 49f, CD106, and CD146. Furthermore, ASCs displayed more pronounced adipogenic differentiation capability relative to BMSC based on Oil Red staining (7 vs. 2.85 fold induction). In contrast, no difference between the stem cell types was detected for osteogenic differentiation based on Alizarin Red staining. Analysis by RT-PCR demonstrated that both the ASC and BMSC differentiated adipocytes and osteoblast displayed a significant upregulation of lineage specific mRNAs relative to the undifferentiated cell populations; no significant differences in fold mRNA induction was noted between ASCs and BMSCs. In conclusion, these results demonstrate human ASCs and BMSCs display distinct immunophenotypes based on surface positivity and expression intensity as well as differences in adipogenic differentiation. The findings support the use of both human ASCs and BMSCs for clinical regenerative medicine. J. Cell. Physiol. © 2010 Wiley-Liss, Inc. PMID: 20857424 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stromal stem cells from adipose tissue and bone marrow of age matched female donors display distinct immunophenotypic profiles. J Cell Physiol. 2010 Sep 20; Authors: Pachón-Peña G, Yu G, Tucker A, Wu X, Vendrell J, Bunnell B, Gimble J Adipose tissue is composed of lipid-filled mature adipocytes and a heterogeneous stromal vascular fraction (SVF) population of cells. Similarly, the bone marrow (BM) is composed of multiple cell types including adipocytes, hematopoietic, osteoprogenitor, and stromal cells necessary to support hematopoiesis. Both adipose and BM contain a population of mesenchymal stromal/stem cells with the potential to differentiate into multiple lineages, including adipogenic, chondrogenic, and myogenic cells, depending on the culture conditions. In this study we have shown that human adipose derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs) populations display a common expression profile for many surface antigens, including CD29, CD49c, CD147, CD166, and HLA-abc. Nevertheless, significant differences were noted in the expression of CD34 and its related protein, PODXL, CD36, CD 49f, CD106, and CD146. Furthermore, ASCs displayed more pronounced adipogenic differentiation capability relative to BMSC based on Oil Red staining (7 vs. 2.85 fold induction). In contrast, no difference between the stem cell types was detected for osteogenic differentiation based on Alizarin Red staining. Analysis by RT-PCR demonstrated that both the ASC and BMSC differentiated adipocytes and osteoblast displayed a significant upregulation of lineage specific mRNAs relative to the undifferentiated cell populations; no significant differences in fold mRNA induction was noted between ASCs and BMSCs. In conclusion, these results demonstrate human ASCs and BMSCs display distinct immunophenotypes based on surface positivity and expression intensity as well as differences in adipogenic differentiation. The findings support the use of both human ASCs and BMSCs for clinical regenerative medicine. J. Cell. Physiol. © 2010 Wiley-Liss, Inc. PMID: 20857424 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nanotechnology: what is it and why is small so big? Can J Ophthalmol. 2010 Oct 20;45(5):1-8 Authors: Leary JF SIZE matters… the size of the scalpel determines the precision of the surgery. Nanotechnology affords us the chance to construct nanotools that are on the size scale of molecules, allowing us to treat each cell of the human body as a patient. Nanomedicine will allow for eradication of disease at the single-cell level. Since nanotools are self-assembling, nanomedicine has the potential to perform parallel processing medicine on a massive scale. These nanotools can be made of biocompatible and biodegradable nanomaterials. They can be “smart” in that they can use sophisticated targeting strategies, which can perform error checking to prevent harm if even a very small fraction of them are mistargeted. Built-in molecular biosensors can provide controlled drug delivery with feedback control for individual cell dosing. If designed to repair existing cells rather than to just destroy diseased cells, these nanomedical devices can perform in-situ regenerative medicine, programming cells along less dangerous cell pathways to prevent tissues and organs from being destroyed by the treatments and thus providing an attractive alternative to allogeneic organ transplants. Nanomedical tools, while tiny in size, can have a huge impact on medicine and health care. Earlier and more sensitive diagnosis will lead to presymptomatic diagnosis and treatment of disease before permanent damage occurs to tissues and organs. This should result in the delivery of better medicine at lower costs with better outcomes. Lastly, and importantly, some of the first uses of nanotechnology and nanomedicine are occurring in the field of ophthalmology. Some of the potential benefits of nanotechnology for future treatment of retinopathies and optic nerve damage are discussed at the end of this paper. PMID: 20856270 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment. Cell Cycle. 2010 Sep 9;9(17) Authors: Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Caro J, Lisanti MP, Sotgia F Recently, using a co-culture system, we demonstrated that MCF7 epithelial cancer cells induce oxidative stress in adjacent cancer-associated fibroblasts, resulting in the autophagic/lysosomal degradation of stromal caveolin-1 (Cav-1). However, the detailed signaling mechanism(s) underlying this process remain largely unknown. Here, we show that hypoxia is sufficient to induce the autophagic degradation of Cav-1 in stromal fibroblasts, which is blocked by the lysosomal inhibitor chloroquine. Concomitant with the hypoxia-induced degradation of Cav-1, we see the upregulation of a number of well-established autophagy/mitophagy markers, namely LC3, ATG16L, BNIP3, BNIP3L, HIF-1α and NFκB. In addition, pharmacological activation of HIF-1α drives Cav-1 degradation, while pharmacological inactivation of HIF-1 prevents the downregulation of Cav-1. Similarly, pharmacological inactivation of NFκB-another inducer of autophagy-prevents Cav-1 degradation. Moreover, treatment with an inhibitor of glutathione synthase, namely BSO, which induces oxidative stress via depletion of the reduced glutathione pool, is sufficient to induce the autophagic degradation of Cav-1. Thus, it appears that oxidative stress mediated induction of HIF1- and NFκB-activation in fibroblasts drives the autophagic degradation of Cav-1. In direct support of this hypothesis, we show that MCF7 cancer cells activate HIF-1α- and NFκB-driven luciferase reporters in adjacent cancer-associated fibroblasts, via a paracrine mechanism. Consistent with these findings, acute knock-down of Cav-1 in stromal fibroblasts, using an siRNA approach, is indeed sufficient to induce autophagy, with the upregulation of both lysosomal and mitophagy markers. How does the loss of stromal Cav-1 and the induction of stromal autophagy affect cancer cell survival? Interestingly, we show that a loss of Cav-1 in stromal fibroblasts protects adjacent cancer cells against apoptotic cell death. Thus, autophagic cancer-associated fibroblasts, in addition to providing recycled nutrients for cancer cell metabolism, also play a protective role in preventing the death of adjacent epithelial cancer cells. We demonstrate that cancer-associated fibroblasts upregulate the expression of TIGAR in adjacent epithelial cancer cells, thereby conferring resistance to apoptosis and autophagy. Finally, the mammary fat pads derived from Cav-1 (-/-) null mice show a hypoxia-like response in vivo, with the upregulation of autophagy markers, such as LC3 and BNIP3L. Taken together, our results provide direct support for the "Autophagic Tumor Stroma Model of Cancer Metabolism", and explain the exceptional prognostic value of a loss of stromal Cav-1 in cancer patients. Thus, a loss of stromal fibroblast Cav-1 is a biomarker for chronic hypoxia, oxidative stress and autophagy in the tumor microenvironment, consistent with its ability to predict early tumor recurrence, lymph node metastasis and tamoxifen-resistance in human breast cancers. Our results imply that cancer patients lacking stromal Cav-1 should benefit from HIF-inhibitors, NFκB-inhibitors, anti-oxidant therapies, as well as autophagy/lysosomal inhibitors. These complementary targeted therapies could be administered either individually or in combination, to prevent the onset of autophagy in the tumor stromal compartment, which results in a "lethal" tumor microenvironment. PMID: 20855962 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats. J Mol Cell Cardiol. 2010 Sep 17; Authors: Fernandes S, Naumova AV, Zhu WZ, Laflamme MA, Gold J, Murry CE BACKGROUND: Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. METHODS AND RESULTS: Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC-only, or non-cardiac human cells in PSC). Histology at 3months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. CONCLUSION: When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model. PMID: 20854826 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Instructive Materials for Functional Tissue Engineering. Macromol Biosci. 2010 Sep 20; Authors: Driessen-Mol A, Bouten CV, Baaijens FP PMID: 20857393 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioactive Scaffolds for Engineering Vascularized Cardiac Tissues. Macromol Biosci. 2010 Sep 20; Authors: Chiu LL, Radisic M, Vunjak-Novakovic G Functional vascularization is a key requirement for the development and function of most tissues, and most critically cardiac muscle. Rapid and irreversible loss of cardiomyocytes during cardiac infarction directly results from the lack of blood supply. Contractile cardiac grafts, engineered using cardiovascular cells in conjunction with biomaterial scaffolds, are an actively studied method for cardiac repair. In this article, we focus on biomaterial scaffolds designed to mediate the development and maturation of vascular networks, by immobilized growth factors. The interactive effects of multiple vasculogenic factors are discussed in the context of cardiac tissue engineering. PMID: 20857391 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Post-Plasma Grafting of AEMA as a Versatile Tool to Biofunctionalise Polyesters for Tissue Engineering. Macromol Biosci. 2010 Sep 20; Authors: Desmet T, Billiet T, Berneel E, Cornelissen R, Schaubroeck D, Schacht E, Dubruel P In the last decade, substantial research in the field of post-plasma grafting surface modification has focussed on the introduction of carboxylic acids on surfaces by grafting acrylic acid (AAc). In the present work, we report on an alternative approach for biomaterial surface functionalisation. Thin poly-ε-caprolactone (PCL) films were subjected to a dielectric barrier discharge Ar-plasma followed by the grafting of 2-aminoethyl methacrylate (AEMA) under UV-irradiation. X-ray photoelectron spectroscopy (XPS) confirmed the presence of nitrogen. The ninhydrin assay demonstrated, both quantitatively and qualitatively, the presence of free amines on the surface. Confocal fluorescence microscopy (CFM), atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to visualise the grafted surfaces, indicating the presence of pAEMA. Static contact angle (SCA) measurements indicated a permanent increase in hydrophilicity. Furthermore, the AEMA grafted surfaces were applied for comparing the physisorption and covalent immobilisation of gelatin. CFM demonstrated that only the covalent immobilisation lead to a complete coverage of the surface. Those gelatin-coated surfaces obtained were further coated using fibronectin. Osteosarcoma cells demonstrated better cell-adhesion and cell-viability on the modified surfaces, compared to the pure PCL films. PMID: 20857390 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Multifunctional Hybrid Three-dimensionally Woven Scaffolds for Cartilage Tissue Engineering. Macromol Biosci. 2010 Sep 20; Authors: Moutos FT, Estes BT, Guilak F The successful replacement of large-scale cartilage defects or osteoarthritic lesions using tissue-engineering approaches will likely require composite biomaterial scaffolds that have biomimetic mechanical properties and can provide cell-instructive cues to control the growth and differentiation of embedded stem or progenitor cells. This study describes a novel method of constructing multifunctional scaffolds for cartilage tissue engineering that can provide both mechanical support and biological stimulation to seeded progenitor cells. 3-D woven PCL scaffolds were infiltrated with a slurry of homogenized CDM of porcine origin, seeded with human ASCs, and cultured for up to 42 d under standard growth conditions. These constructs were compared to scaffolds derived solely from CDM as well as 3-D woven PCL fabric without CDM. While all scaffolds promoted a chondrogenic phenotype of the ASCs, CDM scaffolds showed low compressive and shear moduli and contracted significantly during culture. Fiber-reinforced CDM scaffolds and 3-D woven PCL scaffolds maintained their mechanical properties throughout the culture period, while supporting the accumulation of a cartilaginous extracellular matrix. These findings show that fiber-reinforced hybrid scaffolds can be produced with biomimetic mechanical properties as well as the ability to promote ASC differentiation and chondrogenesis in vitro. PMID: 20857388 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Neurogenic differentiation of human conjunctiva mesenchymal stem cells on a nanofibrous scaffold. Int J Dev Biol. 2010;54(8-9):1295-1300 Authors: Soleimani M, Nadri S, Shabani I The selection of a good quality scaffold is an essential strategy for tissue engineering. Ideally, the scaffold should be a functional and structural biomimetic of the native extracellular matrix and support multiple tissue morphogenesis. However, investigators have previously shown that three-dimensional nanofibrous scaffolds are capable of influencing cellular behavior. In this study, we experimented with a three-dimensional nanofibrous scaffold fabricated from aligned-poly L-lactic acid (PLLA) for its ability to support neurogenic and hinder dopaminergic differentiation of conjunctiva mesenchymal stem cells (CJMSCs) in vitro. In this work, CJMSCs were seeded onto nanofibrous scaffolds, and were induced to differentiate along neurogenic lineages by culturing in specific differentiation media. Scanning electron microscopy imaging, RT-PCR and immunocytochemistry were used to analyze cultivated CJMSCs on scaffold and their expression of neurogenic-specific markers. We found a lack of expression of dopaminergic genes in CJMSCs seeded on align PLLA scaffold, while neurocyte-cell markers including Nestin, NSE, MAP-2 and beta-Tubulin III were expressed in these cells. On the basis of these experimental results, we conclude that the nanofibrous PLLA scaffold reported herein could be used as a potential cell carrier in neural tissue engineering and that these scaffolds could be useful for the partial inhibition of the dopaminergic differentiation of CJMSCs. PMID: 20857376 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Osteoclastic cell behaviors affected by the α-tricalcium phosphate based bone cements. J Mater Sci Mater Med. 2010 Sep 21; Authors: Oh SA, Lee GS, Park JH, Kim HW Calcium phosphate cements (CPCs) have recently gained great interest as injectable bone substitutes for use in dentistry and orthopedics. α-tricalcium phosphate (α-TCP) is a popularly used precursor powder for CPCs. When mixed with appropriate content of liquid and kept under aqueous conditions, α-TCP dissolves to form a calcium-deficient hydroxyapatite and then hardens to cement. In this study, α-TCP based cement (CP) and its composite cement with chitosan (Ch-CP) were prepared and the osteoclastic responses to the cements and their elution products were evaluated. Preliminary evaluation of the cements revealed that the CP and Ch-CP hardened within ~10 min at an appropriate powder-to-liquid ratio (PL) of 3.0. In addition, CP and Ch-CP were transformed into an apatite phase following immersion in a saline solution. Moreover, the osteoblastic cells were viable on the cements for up to 10 days. Mouse-derived bone marrow cells were isolated and activated with osteoclastic differentiation medium, and the effects of the CP and Ch-CP substrates and their ionic eluants on the osteoclastic activity were investigated. Osteoclastic cells were viable for up to 14 days on both types of cements, maintaining a higher cell growth level than the control culture dish. Multi-nucleated osteoclastic cells that were tartrate-resistant acid phosphatase (TRAP)-positive were clearly observed when cultured on the cement substrates as well as treated with the cement eluants. The TRAP activity was found to be significantly higher in cells influenced by the cement substrates and their eluants with respect to the control culture dish (Ch-CP > CP ≫ control). Overall, the osteoclastic differentiation was highly stimulated by the α-TCP based experimental cements in terms of both the substrate interaction and their elution products. PMID: 20857323 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Static and dynamic cultivation of bone marrow stromal cells on biphasic calcium phosphate scaffolds derived from an indirect rapid prototyping technique. J Mater Sci Mater Med. 2010 Sep 21; Authors: Schumacher M, Uhl F, Detsch R, Deisinger U, Ziegler G The adequate regeneration of large bone defects is still a major problem in orthopaedic surgery. Synthetic bone substitute materials have to be biocompatible, biodegradable, osteoconductive and processable into macroporous scaffolds tailored to the patient specific defect. Hydroxyapatite (HA) and tricalcium phosphate (TCP) as well as mixtures of both phases, biphasic calcium phosphate ceramics (BCP), meet all these requirements and are considered to be optimal synthetic bone substitute materials. Rapid prototyping (RP) can be applied to manufacture scaffolds, meeting the criteria required to ensure bone ingrowth such as high porosity and defined pore characteristics. Such scaffolds can be used for bone tissue engineering (BTE), a concept based on the cultivation of osteogenic cells on osteoconductive scaffolds. In this study, scaffolds with interconnecting macroporosity were manufactured from HA, TCP and BCP (60 wt% HA) using an indirect rapid prototyping technique involving wax ink-jet printing. ST-2 bone marrow stromal cells (BMSCs) were seeded onto the scaffolds and cultivated for 17 days under either static or dynamic culture conditions and osteogenic stimulation. While cell number within the scaffold pore system decreased in case of static conditions, dynamic cultivation allowed homogeneous cell growth even within deep pores of large (1,440 mm(3)) scaffolds. Osteogenic cell differentiation was most advanced on BCP scaffolds in both culture systems, while cells cultured under perfusion conditions were generally more differentiated after 17 days. Therefore, scaffolds manufactured from BCP ceramic and seeded with BMSCs using a dynamic culture system are the method of choice for bone tissue engineering. PMID: 20857322 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Silver/poly (lactic acid) nanocomposites: preparation, characterization, and antibacterial activity. Int J Nanomedicine. 2010;5:573-579 Authors: Shameli K, Ahmad MB, Yunus WM, Ibrahim NA, Rahman RA, Jokar M, Darroudi M In this study, antibacterial characteristic of silver/poly (lactic acid) nanocomposite (Ag/PLA-NC) films was investigated, while silver nanoparticles (Ag-NPs) were synthesized into biodegradable PLA via chemical reduction method in diphase solvent. Silver nitrate and sodium borohydride were respectively used as a silver precursor and reducing agent in the PLA, which acted as a polymeric matrix and stabilizer. Meanwhile, the properties of Ag/PLA-NCs were studied as a function of the Ag-NP weight percentages (8, 16, and 32 wt% respectively), in relation to the use of PLA. The morphology of the Ag/PLA-NC films and the distribution of the Ag-NPs were also characterized. The silver ions released from the Ag/PLA-NC films and their antibacterial activities were scrutinized. The antibacterial activities of the Ag/PLA-NC films were examined against Gram-negative bacteria (Escherichia coli and Vibrio parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) by diffusion method using Muller-Hinton agar. The results indicated that Ag/PLA-NC films possessed a strong antibacterial activity with the increase in the percentage of Ag-NPs in the PLA. Thus, Ag/PLA-NC films can be used as an antibacterial scaffold for tissue engineering and medical application. PMID: 20856832 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Implantation of atelocollagen sheet for vocal fold scar. Curr Opin Otolaryngol Head Neck Surg. 2010 Sep 19; Authors: Kishimoto Y, Welham NV, Hirano S PURPOSE OF REVIEW: This article reviews recent advances in scaffold-based interventions for the treatment of vocal fold scarring, with a particular emphasis on atelocollagen sheet implantation in the vocal fold lamina propria. RECENT FINDINGS: Scaffold-based therapies have demonstrated therapeutic promise in both preclinical and early clinical studies. Recent research has begun to shed light on the interactions between scaffold material properties, encapsulated and infiltrating cells, stimulatory molecules such as growth factors, and external regulatory variables such as stress, strain, and vibration. The atelocollagen sheet, a cross-linked collagen material with abundant micropores, has an established clinical track record as a scaffold for dermal and epidermal repair and exhibited potential therapeutic benefit in a recent study of patients with vocal fold scarring and sulcus vocalis. SUMMARY: Scaffolding is one of the useful tools in tissue engineering and atelocollagen sheet implantation has been shown to be effective in vocal fold regeneration. However, many of the scaffold materials under investigation still await clinical translation and those that have been investigated in human patients (such as the atelocollagen sheet) require additional research in appropriately powered placebo-controlled studies. PMID: 20856118 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An update on auricular reconstruction: three major auricular malformations of microtia, prominent ear and cryptotia. Curr Opin Otolaryngol Head Neck Surg. 2010 Sep 19; Authors: Park C, Yoo YS, Hong ST PURPOSE OF REVIEW: Microtia, prominent ear, and cryptotia are the most common types of auricular malformations. This review provides updated information on these types of reconstructions, in addition to recalling previously accepted surgical methods. RECENT FINDINGS: Autogenous costal cartilage is still considered as an ideal material for framework fabrication in microtia reconstruction. Many surgeons have adopted the Nagata approach, the Brent approach, or variations of the two, in their work. With these employed techniques, auricles reconstructed by experienced surgeons have proven to be aesthetically promising. However, with regards to the harvesting of the costal cartilage, the underdevelopment of the chest wall donor site, alopecia of the scalp, and scarring of the postauricular-mastoid region are still considered problematic aspects of these approaches. Some articles have described attempts to solve these problems, whereas some experiments in cartilage production using tissue engineering techniques have shown promise in their initial stages of development.It is generally accepted that prominent ears should be corrected through a combination of sculpting and suture techniques, according to the individual shape and the quality of the ear prominence.Most of the cryptotia malformations show not only embedded upper auricles, but also associated adhesions of the upper auricular cartilage. Their correction should therefore resolve both deformities. SUMMARY: A number of articles highlighting clinical experiences with auricular reconstructions for microtia, prominent ear, and cryptotia have been included in this review. We believe that the information synthesized here will become a basis for further development of auricular reconstruction techniques. PMID: 20856117 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bilateral Orbitozygomatic Reconstruction With Tissue-Engineered Bone. J Craniofac Surg. 2010 Sep;21(5):1612-1614 Authors: Taylor JA Critical defects of the craniomaxillofacial region and long bones are often treated with bone grafts and vascularized osteocutaneous free flaps. These lengthy operations may be associated with considerable donor site morbidity and often have suboptimal functional and aesthetic results. The allure of providing an exact replica of a missing bone that incorporates to become indistinguishable from self, has the capacity to heal and grow, is resistant to infection, and with minimal morbidity is a "holy grail" to all surgeons who work with bone. This is a report of a 14-year-old adolescent boy with Treacher Collins syndrome whose bilateral orbitozygomatic defects were treated with engineered bone made from a combination of human bone allograft, adipose-derived mesenchymal stem cells, bone morphogenic protein-2, and periosteal grafts. This single-stage reconstruction was followed by an exuberant amount of postoperative swelling that persisted for 3 weeks. He had slight lid malposition postoperatively as well but has had no long-term negative effects from the surgery. His reconstruction has remained stable during a 6-month follow-up, and a recent biopsy of the engineered bone demonstrated healthy, lamellar bone. These data are the first to demonstrate revitalization of large volume allograft bone in humans and have positive implications for craniofacial bone tissue engineering. The combination of adipose-derived stem cells, bone morphogenic protein-2, bone allograft, and periosteum may provide an alternative method to both osteocutaneous free flaps and large structural allografts with less morbidity and improved long-term results. PMID: 20856057 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Neovascularization by bFGF releasing hyaluronic acid-gelatin microspheres: in vitro and in vivo studies. Growth Factors. 2010 Sep 21; Authors: Demirdögen B, Elçin AE, Elçin YM Therapeutic angiogenesis with angiogenic growth factors has been described as a promising approach for tissue engineering, wound healing, and for treating ischemic tissues. Here, we assessed the merit of heparin-entrapped hyaluronic acid-gelatin (HA-G) microspheres for the sustained release of recombinant basic fibroblast growth factor (rbFGF) to promote localized neovascularization. HA-G microspheres were prepared by a water-in-oil emulsion method, and the in vitro release kinetics were first examined using three model proteins. Then, bFGF was incorporated into microspheres, and the bioactivity of the in vitro-released rbFGF was tested on human umbilical vein endothelial cell cultures. The ability to promote microvessel growth was assessed in vivo, at the subcutaneous groin fascia of Wistar rats after 3, 7, 14, and 21 days. Histological and morphometrical analysis indicated that heparin-entrapped HA-G microspheres have the capacity to release bioactive rbFGF, leading to localized neovascularization in the rat subcutaneous tissue. PMID: 20854186 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Activation of host tissue trophic factors through JAK/STAT3 signaling: A mechanism of mesenchymal stem cell-mediated cardiac repair. Am J Physiol Heart Circ Physiol. 2010 Sep 17; Authors: Shabbir A, Zisa D, Lin H, Mastri M, Roloff G, Suzuki G, Lee T We recently demonstrated a cardiac therapeutic regimen based on injection of bone marrow mesenchymal stem cells (MSCs) into the skeletal muscle. Although the injected MSCs were trapped in the local musculature, the extracardiac cell delivery approach repaired the failing hamster heart. This finding uncovers a tissue repair mechanism mediated by trophic factors derived from the injected MSCs and local musculature that can be explored for minimally invasive stem cell therapy. However, the trophic factors involved in cardiac repair and their actions remain largely undefined. We demonstrate here a role of MSC-derived IL-6-type cytokines in cardiac repair through engagement of the skeletal muscle JAK/STAT3 axis. The MSC IL-6-type cytokines activated JAK/STAT3 signaling in cultured C2C12 skeletal myocytes and caused increased expression of the STAT3 target genes HGF and VEGF, which was inhibited by gp130 blockade. These in vitro findings were corroborated by in vivo studies, showing that the MSC-injected hamstrings exhibited activated JAK/STAT3 signaling and increased growth factor/cytokine production. Elevated host tissue growth factor levels were also detected in quadriceps, liver, and brain, suggesting a possible global trophic effect. Paracrine actions of these host tissue-derived factors activated the endogenous cardiac repair mechanisms in the diseased heart mediated by AKT, ERK, and JAK/STAT3. Administration of the cell-permeable JAK/STAT inhibitor WP1066 abrogated MSC-mediated host tissue growth factor expression and functional improvement. The study illustrates that the host tissue trophic factor network can be activated by MSC-mediated JAK/STAT3 signaling for tissue repair. PMID: 20852053 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | G-CSF for Stem Cell Therapy in Acute Myocardial Infarction: Friend or Foe? Cardiovasc Res. 2010 Sep 17; Authors: Shim W, Mehta A, Lim SY, Zhang G, Lim CH, Chua T, Wong P Stem cell-based therapy has emerged as a potential therapeutic option for patients with acute myocardial infarction (AMI). The ability of granulocyte colony stimulating factor (G-CSF) to mobilize endogenous stem cells as well as to protect cardiomyocytes at risk via paracrine effects has attracted considerable attention. In the past decade, a number of clinical trials were carried out to study the efficacy of G-CSF in cardiac repair. These trials showed variable outcomes in terms of improved cardiac contractile function and suppressed left ventricular negative remodeling. Critical examinations of these results have raised doubts on the effectiveness of G-CSF in modulating functional recovery. However, these cumulative clinical experiences are helpful in the understanding of mechanisms and roles of signaling pathways in regulating homing and engraftment of bone marrow stem cells (BMSCs) to infarcted heart. In this review, we discuss some of the observations that may have influenced the clinical outcomes. Improving strategies that target the critical aspects of G-CSF driven cardiac therapy may provide a better platform to augment clinical benefits in future trials. PMID: 20851808 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mid term resultas after bone marrow laser revascularization for treating refractory angina. BMC Cardiovasc Disord. 2010 Sep 17;10(1):42 Authors: Reyes G, Allen K, Alvarez P, Alegre A, Aguado B, Oliveras M, Caballero P, Rodriguez J, Duarte J ABSTRACT: BACKGROUND: To evaluate the midterm results of patients with angina and diffuse coronary artery disease treated with transmyocardial revascularization in combination with autologous stem cell therapy. METHODS: Nineteen patients with diffuse coronary artery disease and medically refractory class III/IV angina were evaluated between June 2007 and December 2009 for sole therapy TMR combined with intramyocardial injection of concentrated stem cells. At the time of surgery, autologous bone marrow (120cc) was aspirated from the iliac crest. A cardiac MRI and an isotopic test were performed before and after the procedure. Follow-up was performed by personal interview. RESULTS: There were no perioperative adverse events including no arrhythmias. Mean number of laser channels was 20 and the mean total number of intramyocardially injected cells per milliliter were: total mononuclear cells(83.6 x 106), CD34+ cells(0.6 x 106), and CD133+ cells(0.34 x 106). At 12 months mean follow-up average angina class was significantly improved (3.4 +/- 0.5 vs 1.4 +/- 0.6; p=0.004). In addition, monthly cardiovascular medication usage was significantly decreased (348+/-118 vs. 201+/-92; p=0.001). At six months follow up there was a reduction in the number of cardiac hospital readmissions (2.9+/-2.3 vs. 0.5+/-0.8; p<0.001). MRI showed no alterations regarding LV volumes and a 3% improvement regarding ejection fraction. CONCLUSIONS: The stem cell isolator efficiently concentrated autologous bone marrow derived stem cells while the TMR/stem cell combination delivery device worked uneventfully. An improvement in clinical status was noticed in the midterm follow-up. Images test showed no morphological alterations in the left ventricle after the procedure. PMID: 20849586 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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