|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Biodegradable Elastomers for Tissue Engineering and Cell-Biomaterial Interactions. Macromol Biosci. 2011 Jan 12; Authors: Bettinger CJ Synthetic biomaterials serve as a cornerstone in the development of clinically focused regenerative medicine therapies that aim to reduce suffering and prolong life. Recent improvements in biodegradable elastomeric materials utilize natural extracellular matrix proteins as inspiration to yield a new class of materials with superior degradation kinetics, desirable biocompatibility profiles, and mechanical properties that closely match those of soft tissues. This review describes several classes of synthetic biodegradable elastomers and associated fabrication techniques that are relevant to scaffold development. The application of these materials to select tissue engineering models is also discussed. PMID: 21229578 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Highly efficient multipotent differentiation of human periodontal ligament fibroblasts induced by combined BMP4 and hTERT gene transfer. Gene Ther. 2011 Jan 13; Authors: Mi HW, Lee MC, Fu E, Chow LP, Lin CP Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of stem cell properties. In this study we report for the first time that the combined ectopic expression of BMP4 and hTERT significantly enhanced the multipotent differentiation efficiency and capacity of human PDL fibroblasts (PFs), as shown by osteogenic, adipogenic and neurogenic differentiation in vitro, and cementum/PDL-like tissue regeneration in vivo. These findings may be attributed, at least in part, to the original upregulation of important stem cell markers, such as scleraxis, Stro-1 and CD146, and the extremely lowered threshold for BMP concentration to activate BMP signaling by enhanced basal phosphorylation levels of Smad 1/5/8. In addition, the significantly reduced expression levels of CD146 and CD90 with the presence of Noggin confirms the direct effect of BMP4 on the stem cell-like phenotype of genetically modified PF cells (BT-PFs). Furthermore, BT-PFs exhibited a high neural differentiation capacity (>75%). After transplantation into NOD/SCID mice, genetically modified-PFs generated cementum/PDL-like structures on the surface of the carrier. The multipotency of these modified cells potentially provides an attractive source of stem cells for therapeutic purposes and regenerative medicine.Gene Therapy advance online publication, 13 January 2011; doi:10.1038/gt.2010.158. PMID: 21228880 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hair cycling and wound healing: to pluck or not to pluck? J Invest Dermatol. 2011 Feb;131(2):292-4 Authors: Stojadinovic O, Ito M, Tomic-Canic M The incidence of nonhealing wounds (diabetic foot, pressure, venous, and arterial ulcers) is reaching epidemic proportions, underscoring the need for new treatment modalities. Understanding hair follicle biology and its potential to accelerate wound healing may offer new treatment strategies. In this issue, Ansell et al. show that wounds on anagen skin heal faster than those on telogen skin, suggesting that hair cycle stages may influence healing outcome. PMID: 21228812 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Improvement of Peripheral Nerve Regeneration Following Immunological Demyelination in Vivo. Plast Reconstr Surg. 2011 Jan 11; Authors: Kosins AM, Scholz T, Mendoza C, Lin P, Shepard B, Evans G, Keirstead HS INTRODUCTION:: To improve regeneration of the peripheral nervous system (PNS), we utilize a therapy in the adult rat sciatic nerve in which nerve regeneration is enhanced following acute crush injury. We hypothesize that 1) Axon regeneration within a region of injury increases following experimental, immunological demyelination, and 2) Regenerated axons partially derive from the proximal motor axons. METHODS:: The sciatic nerves of 10 Sprague-Dawley rats were injected with a demyelinating agent following crush injury, while the nerves of 10 control rats received a crush injury without therapy. The sciatic nerves were harvested at 14 and 28 days. The lesion containing length of the nerve was cut into 1mm blocks and specimens were fixed and evaluated using structural and immunohistochemical analyses. A Flouro-Ruby tracer was injected into the sciatic nerves of a separate group of rats to determine the source of axonal re-growth. RESULTS:: An epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 14 days, remyelination was demonstrated spanning the injured sciatic nerve segment. At 28 days, peripheral nerve regeneration was quantified by total axon count, axon density and nerve fiber diameter. Tracers demonstrated that regeneration arose partially from proximal motor axons. CONCLUSION:: This study demonstrates enhanced regeneration in the PNS using experimental, immunological demyelination. Findings indicate that axon count, axon density and nerve fiber diameter within a region of acute crush injury in the rat sciatic nerve can be improved using a demyelinating treatment. PMID: 21228743 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro Effect of Bethanechol and Suberyldicholine on Regions of Guinea Pig Esophagus. J Surg Res. 2010 Dec 18; Authors: Ackbar R, Malvasio V, Holzer P, Saxena AK BACKGROUND: Tissue engineering and regenerative medicine is envisaged as the future option for esophageal replacement; however, engineering of a functional esophagus is impeded by the limited understanding of the anatomical complexity of this dynamic muscular organ. The aim of this study was to characterize the function of native esophageal tissue and determine differences in functional response to stimulation between anatomical sites. MATERIALS AND METHODS: The in-vitro response of guinea pig esophageal preparations, from various anatomical sites, to muscle agonists was investigated. Esophageal strips were exposed to bethanechol, an agonist of muscarinic receptors located on smooth muscle, and suberyldicholine, an agonist of nicotinic receptors located on striated muscle, within a Schuler organ bath, to determine the contractile response on the various segments of the esophagus. RESULTS: The esophagus responded in a reliable and consistent manner to agonist stimulation. Bethanechol dose response curves were constructed with doses of 10 to 300 μM. The average maximal contractions to bethanechol exposure were 4.51, 4.80, 5.55, and 9.15 mN for upper, upper middle, lower middle, and lower esophageal segments, respectively. Responses to singular stimulation with 30 μM suberyldicholine in the presence of tetrodotoxin (100 μM) gave average contractions of 1.07, 0.84, 2.60, and 3.02 mN for upper, upper middle, lower middle, and lower esophageal segments, respectively. Bethanechol and suberyldicholine-induced responses were greater in the lower esophagus in comparison to the upper esophageal segments. CONCLUSION: These findings pave the way for the use of an in-vitro bethanechol and suberyldicholine-induced contraction model for future assessment of engineered esophageal tissue. PMID: 21227463 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic potential of lung epithelial progenitor cells derived from embryonic and induced pluripotent stem cells. Annu Rev Med. 2011 Feb 18;62:95-105 Authors: Wetsel RA, Wang D, Calame DG Embryonic stem (ES) cells derived from preimplantation blastocysts and induced pluripotent stem (iPS) cells generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide a possible unlimited source of cells that could be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. Because of inherent difficulties in deriving endodermal cells from undifferentiated cell cultures, applications using lung epithelial cells derived from ES and iPS cells have lagged behind similar efforts devoted to other tissues, such as the heart and spinal cord. However, during the past several years, significant advances in culture, differentiation, and purification protocols, as well as in bioengineering methodologies, have fueled enthusiasm for the development of stem cell-based lung therapeutics. This article provides an overview of recent research achievements and discusses future technical challenges that must be met before the promise of stem cell applications for lung disease can be realized. PMID: 21226612 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Reprogramming fibroblasts into cardiomyocytes. N Engl J Med. 2011 Jan 13;364(2):177-8 Authors: Murry CE, Pu WT PMID: 21226585 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The role of stem cells in cutaneous wound healing: what do we really know? Plast Reconstr Surg. 2011 Jan;127 Suppl 1:10S-20S Authors: Ko SH, Nauta A, Wong V, Glotzbach J, Gurtner GC, Longaker MT Wound repair is a complex process involving the orchestrated interaction of multiple growth factors, cytokines, chemokines, and cell types. Dysregulation of this process leads to problems such as excessive healing in the form of keloids and hypertrophic scars and chronic, nonhealing wounds. These issues have broad global implications. Stem cells offer enormous potential for enhancing tissue repair and regeneration following injury. The rapidly developing fields of stem cell biology and skin tissue engineering create translational opportunities for the development of novel stem cell-based wound-healing therapies. PMID: 21200267 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | New concepts in liver regeneration. J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:203-12 Authors: Riehle KJ, Dan YY, Campbell JS, Fausto N The unique ability of the liver to regenerate itself has fascinated biologists for years and has made it the prototype for mammalian organ regeneration. Harnessing this process has great potential benefit in the treatment of liver failure and has been the focus of intense research over the past 50 years. Not only will detailed understanding of cell proliferation in response to injury be applicable to other dysfunction of organs, it may also shed light on how cancer develops in a cirrhotic liver, in which there is intense pressure on cells to regenerate. Advances in molecular techniques over the past few decades have led to the identification of many regulatory intermediates, and pushed us onto the verge of an explosive era in regenerative medicine. To date, more than 10 clinical trials have been reported in which augmented regeneration using progenitor cell therapy has been attempted in human patients. This review traces the path that has been taken over the last few decades in the study of liver regeneration, highlights new concepts in the field, and discusses the challenges that still stand between us and clinical therapy. PMID: 21199532 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Genetic modification of T cells. Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S15-20 Authors: Bonini C, Brenner MK, Heslop HE, Morgan RA Adoptively transferred T cells have shown activity in treating viral infections after hemopoietic transplantation and anti-tumor activity against some malignancies such as melanoma and lymphoma. Current research focuses on defining the optimum type of cell for transfer to improve persistence and genetically modifying infused T cells to augment function, overcome tumor evasion strategies and allow ablation should adverse effects occur. PMID: 21195304 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells. 2010 Aug;28(8):1446-55 Authors: Tolar J, Le Blanc K, Keating A, Blazar BR Mesenchymal stromal cells or mesenchymal stem cells (MSCs) have captured considerable scientific and public interest because of their potential to limit physical and immune injury, to produce bioactive molecules and to regenerate tissues. MSCs are phenotypically heterogeneous and distinct subpopulations within MSC cultures are presumed to contribute to tissue repair and the modulation of allogeneic immune responses. As the first example of efficacy, clinical trials for prevention and treatment of graft-versus-host disease after hematopoietic cell transplantation show that MSCs can effectively treat human disease. The view of the mechanisms whereby MSCs function as immunomodulatory and reparative cells has evolved simultaneously. Initially, donor MSCs were thought to replace damaged cells in injured tissues of the recipient. More recently, however, it has become increasingly clear that even transient MSC engraftment may exert favorable effects through the secretion of cytokines and other paracrine factors, which engage and recruit recipient cells in productive tissue repair. Thus, an important reason to investigate MSCs in mechanistic preclinical models and in clinical trials with well-defined end points and controls is to better understand the therapeutic potential of these multifunctional cells. Here, we review the controversies and recent insights into MSC biology, the regulation of alloresponses by MSCs in preclinical models, as well as clinical experience with MSC infusions (Table 1) and the challenges of manufacturing a ready supply of highly defined transplantable MSCs. PMID: 20597105 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection. Retrovirology. 2011 Jan 12;8(1):3 Authors: Nazari-Shafti TZ, Freisinger E, Roy U, Bulot CT, Senst C, Dupin CL, Chaffin AE, Srivastava SK, Mondal D, Alt EU, Izadpanah R ABSTRACT: BACKGROUND: Tissue resident mesenchymal stem cells (MSCs) are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. The ability of single cell clones isolated from adipose tissue resident MSCs (ASCs) to differentiate into cells of hematopoietic lineage has been previously demonstrated. In the present study, we investigated if the hematopoietic differentiated (HD) cells derived from ASCs could productively be infected with HIV-1. RESULTS: HD cells were generated by differentiating clonally expanded cultures of adherent subsets of ASCs (CD90+, CD105+, CD45-, and CD34-). Transcriptome analysis revealed that HD cells acquire a number of elements that increase their susceptibility for HIV-1 infection, including HIV-1 receptor/co-receptor and other key cellular cofactors. HIV-1 infected HD cells (HD-HIV) showed elevated p24 protein and gag and tat gene expression, implying a high and productive infection. HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC. HIV-1 restricting factors like APOBEC3F and TRIM5 also showed up regulation. HIV-1 infection increased apoptosis and cell cycle regulatory genes in HD cells. Although undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10. CONCLUSIONS: Considering the presence of profuse amounts of ASCs in different tissues, these findings suggest the possible role that could be played by HD cells derived from ASCs in HIV-1 infection. The undifferentiated ASCs were non-permissive to HIV-1 infection; however, HIV-1 exposure increased the expression of some hematopoietic lineage related genes. The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies. PMID: 21226936 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Lineage-specific promoter DNA methylation patterns segregate adult progenitor cell types. Stem Cells Dev. 2010 Aug;19(8):1257-66 Authors: Sørensen AL, Timoskainen S, West FD, Vekterud K, Boquest AC, Ahrlund-Richter L, Stice SL, Collas P Mesenchymal stem cells (MSCs) can differentiate into multiple mesodermal cell types in vitro; however, their differentiation capacity is influenced by their tissue of origin. To what extent epigenetic information on promoters of lineage-specification genes in human progenitors influences transcriptional activation and differentiation potential remains unclear. We produced bisulfite sequencing maps of DNA methylation in adipogenic, myogenic, and endothelial promoters in relation to gene expression and differentiation capacity, and unravel a similarity in DNA methylation profiles between MSCs isolated from human adipose tissue, bone marrow (BM), and muscle. This similarity is irrespective of promoter CpG content. Methylation patterns of MSCs are distinct from those of hematopoietic progenitor cells (HPCs), pluripotent human embryonic stem cells (hESCs), and multipotent hESC-derived mesenchymal cells (MCs). Moreover, in vitro MSC differentiation does not affect lineage-specific promoter methylation states, arguing that these methylation patterns in differentiated cells are already established at the progenitor stage. Further, we find a correlation between lineage-specific promoter hypermethylation and lack of differentiation capacity toward that lineage, but no relationship between weak promoter methylation and capacity of transcriptional activation or differentiation. Thus, only part of the restriction in differentiation capacity of tissue-specific stem cells is programmed by promoter DNA methylation: hypermethylation seems to constitute a barrier to differentiation, however, no or weak methylation has no predictive value for differentiation potential. PMID: 19886822 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Not a process of simple vicariousness, the differentiation of human adipose-derived mesenchymal stem cells to renal tubular epithelial cells plays an important role in acute kidney injury repairing. Stem Cells Dev. 2010 Aug;19(8):1267-75 Authors: Li K, Han Q, Yan X, Liao L, Zhao RC The recent findings indicate that under conditions of severe tubular injuries, transplantation of mesenchymal stem cells (MSCs) may be a promising treatment in acute kidney diseases; nevertheless, the underling mechanism is still under debate. To investigate the differentiation characteristics and the role of MSCs in renal tubular injury, human adipose-derived MSCs (hAD-MSCs) were transplanted into ischemia-reperfusion (I/R) kidneys in C57BL/6 mouse model. Results showed that hAD-MSCs were able to differentiate toward renal tubular epithelium at an early stage of injuries. The differentiated donor cells replaced the vacant space left over by the dead cells, contributed to maintenance of structural integrity and proceeded to a subsequent tissue repair process. Furthermore, MSCs as supportive cells may promote repair via secreting cytokines. The differentiation and replacement of MSCs at an extremely early stage play important roles for the subsequent self-repair and -renewal of functional cells. Direct differentiation of MSCs, as an important mechanism of injured kidney repair, warrants further investigation. PMID: 19874085 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | The botched bid by Robert Klein, chairman of the California stem cell agency, to hand pick his successor was revisited in the January issue of Nature Medicine.
The article is a briefer version of what Elie Dolgin filed last month on the Internet. The headline on the magazine article reads, "Nomination bungle leaves CIRM leadership in limbo."
Dolgin again reported that the Alan Bernstein, | | | | | | | | | | | | | | | | | | | | | | | | | Biodegradable Elastomers for Tissue Engineering and Cell-Biomaterial Interactions. Macromol Biosci. 2011 Jan 12; Authors: Bettinger CJ Synthetic biomaterials serve as a cornerstone in the development of clinically focused regenerative medicine therapies that aim to reduce suffering and prolong life. Recent improvements in biodegradable elastomeric materials utilize natural extracellular matrix proteins as inspiration to yield a new class of materials with superior degradation kinetics, desirable biocompatibility profiles, and mechanical properties that closely match those of soft tissues. This review describes several classes of synthetic biodegradable elastomers and associated fabrication techniques that are relevant to scaffold development. The application of these materials to select tissue engineering models is also discussed. PMID: 21229578 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Permeability study of vertebral cancellous bone using micro-computational fluid dynamics. Comput Methods Biomech Biomed Engin. 2011 Jan 1;:1 Authors: Teo JC, Teoh SH Understanding of cancellous bone permeability is lacking despite its importance in designing tissue engineering scaffolds for bone regeneration and orthopaedic surgery that relies on infiltration of bone cement into porous cancellous bone. We employed micro-computational fluid dynamics to investigate permeability for 37 cancellous bone specimens, eliminating stringent technical requirements of bench-top testing. Microarchitectural parameters were also determined for the specimens and correlated, using uni-variate and multi-variate regression analyses, against permeability. We determined that bone surface density, trabecular pattern factor, structure model index and trabecular number are other possible predictors of permeability (with R values of 0.47, 0.44, 0.40 and 0.33), in addition to the commonly used porosity parameter (R value of 0.38). Pooling these parameters and performing multi-variate linear regression analysis improved yield the R-value of 0.50, indicating that porosity alone is a poor predictor of cancellous bone permeability and, therefore, other parameters should be included for a better and improved linear model. PMID: 21229410 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Evaluation of RPE65, CRALBP, VEGF, CD68, and Tyrosinase Gene Expression in Human Retinal Pigment Epithelial Cells Cultured on Amniotic Membrane. Biochem Genet. 2011 Jan 13; Authors: Akrami H, Soheili ZS, Sadeghizadeh M, Khalooghi K, Ahmadieh H, Kanavi MR, Samiei S, Pakravesh J The retinal pigment epithelium (RPE) plays a key role in the maintenance of the normal functions of the retina. Tissue engineering using amniotic membrane as a substrate to culture RPE cells may provide a promising new strategy to replace damaged RPE. We established a method of culturing RPE cells over the amniotic membrane as a support for their growth and transplantation. The transcription of specific genes involved in cellular function of native RPE, including RPE65, CRALBP, VEGF, CD68, and tyrosinase, were then measured using quantitative real-time PCR. Data showed a considerable increase in transcription of RPE65, CD68, and VEGF in RPE cells cultured on amniotic membrane. The amounts of CRALBP and tyrosinase transcripts were not affected. This may simply indicate that amniotic membrane restricted dedifferentiation of RPE cells in culture. The results suggest that amniotic membrane may be considered as an elective biological substrate for RPE cell culture. PMID: 21229300 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Green synthesis of gold nanoparticles using Nyctanthes arbortristis flower extract. Bioprocess Biosyst Eng. 2011 Jan 13; Authors: Das RK, Gogoi N, Bora U The present study explores the reducing and capping potentials of ethanolic flower extract of the plant Nyctanthes arbortristis for the synthesis of gold nanoparticles. The extract at different volume fractions were stirred with HAuCl(4) aqueous solution at 80 °C for 30 min. The UV-Vis spectroscopic analysis of the reaction products confirmed successful reduction of Au(3+) ions to gold nanoparticles. Transmission electron microscope (TEM) revealed dominant spherical morphology of the gold nanoparticles with an average diameter of 19.8 ± 5.0 nm. X-ray diffraction (XRD) study confirmed crystalline nature of the synthesized particles. Fourier transform infra-red (FTIR) and nuclear magnetic resonance (NMR) analysis of the purified and lyophilized gold nanoparticles confirmed the surface adsorption of biomolecules during preparation and caused long-term (6 months) stability. Low reaction temperature (25 °C) favored anisotropy. The strong reducing power of the flower extract can also be tested in the green synthesis of other metallic nanoparticles. PMID: 21229266 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Improvement of Peripheral Nerve Regeneration Following Immunological Demyelination in Vivo. Plast Reconstr Surg. 2011 Jan 11; Authors: Kosins AM, Scholz T, Mendoza C, Lin P, Shepard B, Evans G, Keirstead HS INTRODUCTION:: To improve regeneration of the peripheral nervous system (PNS), we utilize a therapy in the adult rat sciatic nerve in which nerve regeneration is enhanced following acute crush injury. We hypothesize that 1) Axon regeneration within a region of injury increases following experimental, immunological demyelination, and 2) Regenerated axons partially derive from the proximal motor axons. METHODS:: The sciatic nerves of 10 Sprague-Dawley rats were injected with a demyelinating agent following crush injury, while the nerves of 10 control rats received a crush injury without therapy. The sciatic nerves were harvested at 14 and 28 days. The lesion containing length of the nerve was cut into 1mm blocks and specimens were fixed and evaluated using structural and immunohistochemical analyses. A Flouro-Ruby tracer was injected into the sciatic nerves of a separate group of rats to determine the source of axonal re-growth. RESULTS:: An epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 14 days, remyelination was demonstrated spanning the injured sciatic nerve segment. At 28 days, peripheral nerve regeneration was quantified by total axon count, axon density and nerve fiber diameter. Tracers demonstrated that regeneration arose partially from proximal motor axons. CONCLUSION:: This study demonstrates enhanced regeneration in the PNS using experimental, immunological demyelination. Findings indicate that axon count, axon density and nerve fiber diameter within a region of acute crush injury in the rat sciatic nerve can be improved using a demyelinating treatment. PMID: 21228743 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biocompatibility of Different Poly(Lactide-Coglycolide) Polymers Implanted into the Subconjunctival Space in Rats. Ophthalmic Res. 2011 Jan 11;46(2):55-65 Authors: Rönkkö S, Kaarniranta K, Kalesnykas G, Uusitalo H Aims: Biomaterials are widely used in ophthalmology, and biodegradable polymers have been evaluated for use in surgery, tissue engineering and targeted drug delivery. We examined the tissue reactions attributable to 3 biodegradable polymers in the rat eye. Methods: Inion GTR™ membrane [a blend of 85:15 poly(L-lactide-coglycolide) and 70:30 poly(L-lactide-co-1,3-trimethylene carbonate) copolymers in a molar ratio of 70:30], a 50:50 molar ratio of poly(DL-lactide-coglycolide) (PDLGA 50:50), and a 85:15 molar ratio of poly(DL-lactide-coglycolide) (PDLGA 85:15) were surgically implanted into the subconjuctival space of rat eyes. Biocompatibility was evaluated by following the eyes clinically and with histo- and immunohistochemical techniques. Results: No clinical signs of inflammation were observed around the implants during follow-up. However, immunohistochemical sections revealed increased accumulation of magrophages around PDLGA 85:15 at 2 weeks and of myofibroblasts around GTR membrane material at 1 month. The order of the degradation time of the material was GTR membrane material > PDLGA 85:15 > PDLGA 50:50; Fourier transform infrared microscopy revealed some differences in the degradation behavior of the polymers. Immunohistochemical staining for plasma or cellular fibronectin was observed around all implants. Conclusions: Despite the different decay times and influences on the expression levels of fibronectins, all polymers evoked rather similar tissue reactions during the observation period. This study provides new data on the biocompatibility of biomaterials in rat eyes. Our findings of the tissue decay of the implant and biomaterial-induced tissue reaction may help in the development of better biomaterials for eye surgery with optimal drug delivery properties. PMID: 21228610 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cell adhesive and growth behavior on electrospun nanofibrous scaffolds by designed multifunctional composites. Colloids Surf B Biointerfaces. 2010 Dec 21; Authors: Cao D, Wu YP, Fu ZF, Tian Y, Li CJ, Gao CY, Chen ZL, Feng XZ Nanostructured biocomposite scaffolds of poly(l-lactide) (PLLA) blended with collagen (coll) or hydroxyapatite (HA), or both for tissue engineering application, were fabricated by electrospinning. The electrospun scaffolds were characterized for the morphology, chemical and tensile properties by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA), Fourier transform infrared (FTIR) measurement, and tensile testing. Electrospun biocomposite scaffolds of PLLA and collagen or (and) HA in the diameter range of 200-700nm mimic the nanoscale structure of the extracellular matrix (ECM) with a well-interconnection pore network structure. The presence of collagen in the scaffolds increased their hydrophility, and enhanced cell attachment and proliferation, while HA improved the tensile properties of the scaffolds. The biocompatibility of the electrospun scaffolds and the viability of contacting cells were evaluated by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) nuclear staining and by fluorescein diacetate (FDA) and propidium iodide (PI) double staining methods. The results support the conclusion that 293T cells grew well on composite scaffolds. Compared with pure PLLA scaffolds a greater density of viable cells was seen on the composites, especially the PLLA/HA/collagen scaffolds. PMID: 21227659 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro Effect of Bethanechol and Suberyldicholine on Regions of Guinea Pig Esophagus. J Surg Res. 2010 Dec 18; Authors: Ackbar R, Malvasio V, Holzer P, Saxena AK BACKGROUND: Tissue engineering and regenerative medicine is envisaged as the future option for esophageal replacement; however, engineering of a functional esophagus is impeded by the limited understanding of the anatomical complexity of this dynamic muscular organ. The aim of this study was to characterize the function of native esophageal tissue and determine differences in functional response to stimulation between anatomical sites. MATERIALS AND METHODS: The in-vitro response of guinea pig esophageal preparations, from various anatomical sites, to muscle agonists was investigated. Esophageal strips were exposed to bethanechol, an agonist of muscarinic receptors located on smooth muscle, and suberyldicholine, an agonist of nicotinic receptors located on striated muscle, within a Schuler organ bath, to determine the contractile response on the various segments of the esophagus. RESULTS: The esophagus responded in a reliable and consistent manner to agonist stimulation. Bethanechol dose response curves were constructed with doses of 10 to 300 μM. The average maximal contractions to bethanechol exposure were 4.51, 4.80, 5.55, and 9.15 mN for upper, upper middle, lower middle, and lower esophageal segments, respectively. Responses to singular stimulation with 30 μM suberyldicholine in the presence of tetrodotoxin (100 μM) gave average contractions of 1.07, 0.84, 2.60, and 3.02 mN for upper, upper middle, lower middle, and lower esophageal segments, respectively. Bethanechol and suberyldicholine-induced responses were greater in the lower esophagus in comparison to the upper esophageal segments. CONCLUSION: These findings pave the way for the use of an in-vitro bethanechol and suberyldicholine-induced contraction model for future assessment of engineered esophageal tissue. PMID: 21227463 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Comparative analysis of in vitro osteo/odontogenic differentiation potential of human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAP). Arch Oral Biol. 2011 Jan 10; Authors: Bakopoulou A, Leyhausen G, Volk J, Tsiftsoglou A, Garefis P, Koidis P, Geurtsen W OBJECTIVE: The aim of this study was to compare the in vitro osteo/odontogenic differentiation potential of mesenchymal stem cells (MSCs) derived from the dental pulp (dental pulp stem cells - DPSCs) or the apical papilla (stem cells from the apical papilla - SCAP) of permanent developing teeth. DESIGN: DPSCs and SCAP cultures were established from impacted third molars of young healthy donors at the stage of root development. Cultures were analysed for stem cell markers, including STRO-1, CD146, CD34 and CD45 using flow cytometry. Cells were then induced for osteo/odontogenic differentiation by media containing dexamethasone, KH(2)PO(4) and β-glycerophosphate. Cultures were analysed for morphology, growth characteristics, mineralization potential (Alizarin Red method) and differentiation markers (dentine sialophosphoprotein-DSPP, bone sialoprotein-BSP, osteocalcin-OCN, alkaline phosphatase-ALP), using immunocytochemistry and reverse transcriptase-polymerase chain reaction. RESULTS: All DPSCs and SCAP cultures were positive for STRO-1, CD146 and CD34, in percentages varying according to cell type and donor, but negative for CD45. Both types of MSCs displayed an active potential for cellular migration, organization and mineralization, producing 3D mineralized structures. These structures progressively expressed differentiation markers, including DSPP, BSP, OCN, ALP, having the characteristics of osteodentin. SCAP, however, showed a significantly higher proliferation rate and mineralization potential, which might be of significance for their use in bone/dental tissue engineering. CONCLUSIONS: This study provides evidence that different types of dental MSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source for osteo/odontogenic differentiation and biomineralization that could be further applied for stem cell-based clinical therapies. PMID: 21227403 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Orthodontic tooth movement in alveolar cleft repaired with a tissue engineering bone: An experimental study in dogs. Tissue Eng Part A. 2011 Jan 12; Authors: Zhang D, Chu F, Yang Y, Xia L, Zeng D, Zhang X, Uludağ H, Qian Y, Jiang X Tissue engineering approaches have been successfully used in repairing bone defects and have become a viable alternative to autologous bone. The aim of the present study was to investigate if a construct of porous β-tricalcium phosphate (β-TCP) combined with osteogenically induced bone marrow stromal cells (bMSCs) could repair alveolar cleft, and allow for subsequent orthodontic tooth movement in a canine model. Twelve alveolar osteotomy surgeries in six animals were made bilaterally and randomly implanted by (i) tissue-engineered bone complex of bMSCs/β-TCP (Group A, n=4), (ii)β-TCP alone (Group B, n=4), and (iii) autologous bone obtained from iliac bone (Group C, n=4). Contralateral alveolar defects were created in one animal and left untreated to serve as blank control to observe spontaneous healing of the defects. Sequential fluorescent labeling and radiographic observation was used to evaluate new bone formation and mineralization in each defect. Orthodontic tooth movement was initiated 8 weeks after surgical operation for 12 weeks, and then the dogs were sacrificed for histological and histomorphometric analysis. Results indicated that the tissue-engineered complex with bMSCs/β-TCP dramatically promoted new bone formation and mineralization and achieved a favorable height of the repaired alveolar when compared with β-TCP alone, which absorbed severely. The overall effect of the tissue-engineered bone was equivalent to autologous bone; the physiological function of the alveolar bone was restored by allowing the adjacent teeth to move into the newly formed bone in the grafted region. This study demonstrated that the tissue engineering bone from the combination of β-TCP and bMSCs is a feasible clinical approach for patients with alveolar cleft and the subsequent orthodontic tooth movement. KEY WORDS: alveolar cleft; tissue-engineered bone; β-tricalcium phosphate; bone marrow stromal cells; orthodontic tooth movement. PMID: 21226625 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Research progress of scaffold materials in skeletal muscle tissue engineering]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 Nov;24(11):1386-91 Authors: Huang W, Liao H To review the current researches of scaffold materials for skeletal muscle tissue engineering, to predict the development trend of scaffold materials in skeletal muscle tissue engineering in future. PMID: 21226367 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Progress of peripheral nerve defect treatment with tissue engineering]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 Nov;24(11):1310-4 Authors: Yang Y, Bo Z To review new progress of related research of peripheral nerve defect treatment with tissue engineering in recent years. PMID: 21226351 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Functional evaluation of chemically extracted acellular nerve allograft supplement with different tissues of Schwann cells for peripheral nerve regeneration]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 Nov;24(11):1281-7 Authors: Zhao Z, Zhao B, Wang Y, Peng J, Zhang L, Chen J, Zhao Q, Ren Z, Liu Y, Xu W, Lu S To construct chemically extracted acellular nerve allograft (CEANA) with Schwann cells (SCs) from different tissues and to compare the effect of repairing peripheral nerve defect. PMID: 21226345 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Bioengineered skin constructs and their use in wound healing. Plast Reconstr Surg. 2011 Jan;127 Suppl 1:75S-90S Authors: Lazic T, Falanga V Over the past two decades, the field of wound healing and tissue repair has witnessed tremendous advances resulting from the biological sciences, biomedical and tissue engineering, and greater clinical understanding of wounds and their pathophysiology. In large part because of these advances, clinicians are now able to offer and deliver more sophisticated and effective treatments to patients with acute wounds, chronic wounds, burns, and other types of injuries. PMID: 21200276 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The role of stem cells in cutaneous wound healing: what do we really know? Plast Reconstr Surg. 2011 Jan;127 Suppl 1:10S-20S Authors: Ko SH, Nauta A, Wong V, Glotzbach J, Gurtner GC, Longaker MT Wound repair is a complex process involving the orchestrated interaction of multiple growth factors, cytokines, chemokines, and cell types. Dysregulation of this process leads to problems such as excessive healing in the form of keloids and hypertrophic scars and chronic, nonhealing wounds. These issues have broad global implications. Stem cells offer enormous potential for enhancing tissue repair and regeneration following injury. The rapidly developing fields of stem cell biology and skin tissue engineering create translational opportunities for the development of novel stem cell-based wound-healing therapies. PMID: 21200267 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC. Colloids Surf B Biointerfaces. 2010 Dec 1;81(2):412-21 Authors: Gonzalez-Mira E, Egea MA, Garcia ML, Souto EB Packaging small drug molecules, such as non-steroidal anti-inflammatory drugs (NSAIDs) into nanoparticulate systems has been reported as a promising approach to improve the drug's bioavailability, biocompatibility and safety profiles. In the last 20 years, lipid nanoparticles (lipid dispersions) entered the nanoparticulate library as novel carrier systems due to their great potential as an alternative to other systems such as polymeric nanoparticles and liposomes for several administration routes. For ocular instillation nanoparticulate carriers are required to have a low mean particle size, with the lowest polydispersity as possible. The purpose of this work was to study the combined influence of 2-level, 4-factor variables on the formulation of flurbiprofen (FB), a lipophilic NSAID, in lipid carriers currently named as nanostructured lipid carriers (NLC). NLC were produced with stearic acid (SA) and castor oil (CO) stabilized by Tween® 80 (non-ionic surfactant) in aqueous dispersion. A 2(4) full factorial design based on 4 independent variables was used to plan the experiments, namely, the percentage of SA with regard to the total lipid, the FB concentration, the stabilizer concentration, and the storage conditions (i.e., storage temperature). The effects of these parameters on the mean particle size, polydispersity index (PI) and zeta potential (ZP) were investigated as dependent variables. The optimization process was achieved and the best formulation corresponded to the NLC formulation composed of 0.05 (wt%) FB, 1.6 (wt%) Tween® 80 and a 50:50 ratio of SA to CO, with an average diameter of 288 nm, PI 0.245 of and ZP of -29 mV. This factorial design study has proven to be a useful tool in optimizing FB-loaded NLC formulations. Stability of the optimized NLC was predicted using a TurbiScanLab® and the ocular tolerance was assessed in vitro and in vivo by the Eytex® and Draize test, respectively. The developed systems were shown physico-chemically stable with high tolerance for eye instillation. PMID: 20719479 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Scaling the heights--challenges in medical materials. J R Soc Interface. 2010 Oct 6;7 Suppl 5:S501-2 Authors: Edirisinghe M, Stride E PMID: 20667845 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Applications of conducting polymers and their issues in biomedical engineering. J R Soc Interface. 2010 Oct 6;7 Suppl 5:S559-79 Authors: Ravichandran R, Sundarrajan S, Venugopal JR, Mukherjee S, Ramakrishna S Conducting polymers (CPs) have attracted much interest as suitable matrices of biomolecules and have been used to enhance the stability, speed and sensitivity of various biomedical devices. Moreover, CPs are inexpensive, easy to synthesize and versatile because their properties can be readily modulated by (i) surface functionalization techniques and (ii) the use of a wide range of molecules that can be entrapped or used as dopants. This paper discusses the various surface modifications of the CP that can be employed in order to impart physico-chemical and biological guidance cues that promote cell adhesion/proliferation at the polymer-tissue interface. This ability of the CP to induce various cellular mechanisms widens its applications in medical fields and bioengineering. PMID: 20610422 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The degradation properties of co-continuous calcium phosphate polyester composites: insights with synchrotron micro-computer tomography. J R Soc Interface. 2010 Oct 6;7 Suppl 5:S663-74 Authors: Ehrenfried LM, Farrar D, Cameron RE This study investigates the in vitro degradation properties of composites consisting of a porous tricalcium phosphate (TCP) foam filled with degradable poly(dl-lactic acid) (PDLLA) via either in situ polymerization or infiltration. The motivation was to develop a material for bone repair that would be initially mechanically strong and would develop porosity during degradation of one of the components. A thorough analysis of the physical in vitro degradation properties has been conducted and reported by the same authors elsewhere. Synchrotron micro-computer tomography analysis (conducted at ID19, ESRF, Grenoble, France) allowed detailed insights to be gained into the process of the composites' degradation, which was discovered to be strongly influenced by the manufacturing method. The polymer phase of in situ-polymerized TCP-PDLLA degraded as a bulk sample, with faster degradation in the centre of the sample as a whole. In contrast, the polymer phase of infiltrated TCP-PDLLA degraded as individual polymer spheres with faster degradation in the centre of each sphere. PMID: 20538756 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Silica-collagen bionanocomposites as three-dimensional scaffolds for fibroblast immobilization. Acta Biomater. 2010 Oct;6(10):3998-4004 Authors: Desimone MF, Hélary C, Rietveld IB, Bataille I, Mosser G, Giraud-Guille MM, Livage J, Coradin T Silica-collagen bionanocomposite hydrogels were obtained by addition of silica nanoparticles to a protein suspension followed by neutralization. Electron microscopy studies indicated that larger silica nanoparticles (80 nm) do not interact strongly with collagen, whereas smaller ones (12 nm) form rosaries along the protein fibers. However, the composite network structurally evolved with time due to the contraction of the cells and the dissolution of the silica nanoparticles. When compared to classical collagen hydrogels, these bionanocomposite materials showed lower surface contraction in the short term (1 week) and higher viability of entrapped cells in the long term (3 weeks). A low level of gelatinase MMP2 enzyme expression was also found after this period. Several proteins involved in the catabolic and anabolic activity of the cells could also be observed by immunodetection techniques. All these data suggest that the bionanocomposite matrices constitute a suitable environment for fibroblast adhesion, proliferation and biological activity and therefore constitute an original three-dimensional environment for in vitro cell culture and in vivo applications, in particular as biological dressings. PMID: 20493975 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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