|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Therapeutic opportunities: Telomere maintenance in inducible pluripotent stem cells. Mutat Res. 2011 May 13; Authors: Gourronc FA, Klingelhutz AJ It has been demonstrated that exogenous expression of a combination of transcription factors can reprogram differentiated cells such as fibroblasts and keratinocytes into what have been termed induced pluripotent stem (iPS) cells. These iPS cells are capable of differentiating into all the tissue lineages when placed in the right environment and, in the case of mouse cells, can generate chimeric mice and be transmitted through the germline. Safer and more efficient methods of reprogramming are rapidly being developed. Clearly, iPS cells present a number of exciting possibilities, including disease modeling and therapy. A major question is whether the nuclei of iPS cells are truly rejuvenated or whether they might retain some of the marks of aging from the cells from which they were derived. One measure of cellular aging is the telomere. In this regard, recent studies have demonstrated that telomeres in iPS cells may be rejuvenated. They are not only elongated by reactivated telomerase but they are also epigenetically modified to be similar but not identical to embryonic stem cells. Upon differentiation, the derivative cells turn down telomerase, the telomeres begin to shorten again, and the telomeres and the genome are returned to an epigenetic state that is similar to normal differentiated somatic cells. While these preliminary telomere findings are promising, the overall genomic integrity of reprogrammed cells may still be problematic and further studies are needed to examine the safety and feasibility of using iPS cells in regenerative medicine applications. PMID: 21605571 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal Stem Cell (Msc) Mediated Delivery of the Sodium Iodide Symporter (Nis) Supports Radionuclide Imaging and Treatment of Breast Cancer. Stem Cells. 2011 May 23; Authors: Dwyer RM, Ryan J, Havelin RJ, Morris JC, Miller BW, Liu Z, Flavin R, O'Flatharta C, Foley MJ, Barrett HH, Murphy JM, Barry FP, O'Brien T, Kerin MJ Mesenchymal Stem Cells (MSCs) migrate specifically to tumors in vivo, and coupled with their capacity to bypass immune surveillance, are attractive vehicles for tumor-targeted delivery of therapeutic agents. This study aimed to introduce MSC-mediated expression of the sodium iodide symporter (NIS) for imaging and therapy of breast cancer. Tumor bearing animals received an intravenous or intratumoral injection of NIS expressing MSCs (MSC-NIS), followed by (99m) TcO(4) (-) imaging 3-14Days (D) later using a BazookaSPECT γ-camera. Tissue was harvested for analysis of hNIS expression by RQ-PCR. Therapy animals received an intraperitoneal injection of (131) I or saline 14D following injection of MSC-NIS, and tumor volume was monitored for 8 weeks. BazookaSPECT imaging following injection of MSC-NIS revealed an image of animal intestines and chest area at D3, with a weak tumor image also visible. By D14, the tumor was visible with a significant reduction in radionuclide accumulation in non-target tissue observed. hNIS gene expression was detected in the intestines, heart, lungs and tumor at early timepoints but later depleted in non-target tissues and persisted at the tumor site. Based on imaging/biodistribution data, animals received a therapeutic dose of (131) I 14D following MSC-NIS injection. This resulted in a significant reduction in tumor growth (Mean ± SEM, 236 ± 62mm(3) versus 665 ± 204 mm(3) in controls). The ability to non-invasively track MSC migration and transgene expression in real time prior to therapy is a major advantage to this strategy. This promising data supports the feasibility of this approach as a novel therapy for breast cancer. PMID: 21608083 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [New applications and the comparison between atomic force microscope and electron microscope in regenerative medicine]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2011 Apr;28(2):396-400 Authors: Shi Y, Cai J This article introduces the basic theories about atomic force microscope (AFM) and electron microscope (EM), respectively. New applications of each microscopic technology in regenerative medicine, covering both material science and life science, are discussed. The advantages or disadvantages of the kinds of microscopes in working conditions, sample preparation, resolution and the like, are discussed and compared systematically to make clear each scope of applications. This could be a useful guide for selecting the appropriate microscopic analysis in research work about regenerative medicine. PMID: 21604509 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Premutation CGG-repeat expansion of the Fmr1 gene impairs mouse neocortical development. Hum Mol Genet. 2011 Jan 1;20(1):64-79 Authors: Cunningham CL, Martínez Cerdeño V, Navarro Porras E, Prakash AN, Angelastro JM, Willemsen R, Hagerman PJ, Pessah IN, Berman RF, Noctor SC Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder caused by a premutation CGG-trinucleotide repeat expansion (55-200 CGG repeats) within the 5'-untranslated region of the FMR1 gene. Although FXTAS generally affects premutation carriers over 50 years of age, cognitive and psychological symptoms can appear in carriers during childhood, suggesting that the FMR1 premutation affects brain function early in life. Recent work with cultured hippocampal neurons from a premutation (Fmr1 CGG knock-in) mouse model revealed impaired development of early postnatal neurons, consistent with the developmental clinical involvement of premutation carriers. In the current work, we show that the presence of premutation CGG-repeat expansions in the mouse Fmr1 gene alters embryonic neocortical development. Specifically, embryonic premutation mice display migration defects in the neocortex and altered expression of neuronal lineage markers. The current data demonstrate that premutation alleles of the Fmr1 gene are associated with defects in developmental programs operating during prenatal stages of brain formation and provide further evidence that the FMR1 premutation has a neurodevelopmental component. PMID: 20935171 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiovascular System During the Postpartum State in Women With a History of Preeclampsia. Hypertension. 2011 May 23; Authors: Evans CS, Gooch L, Flotta D, Lykins D, Powers RW, Landsittel D, Roberts JM, Shroff SG In subjects with previous preeclampsia, differences in cardiovascular and/or blood biochemical parameters are present in the nonpregnant state, and a simultaneous assessment of multiple derived indices better differentiates between women with or without previous preeclampsia. We examined 18 previous preeclamptic and 50 previous uncomplicated pregnancies, ≈16 months postpartum. Cardiovascular assessment included the following: (1) systemic hemodynamics and mechanics (Doppler echocardiography, tonometry, and oscillometric sphygmomanometry); (2) endothelial function (plethysmography); (3) left ventricular properties (echocardiography); and (4) blood biochemical analyses. Compared to women with previous uncomplicated pregnancies, previous preeclamptics had higher mean (80±1 versus 86±3 mm Hg; P=0.04) and diastolic (64±1 versus 68±2 mm Hg; P=0.04) pressures and total vascular resistance (1562±37 versus 1784±114 dyne · s/cm(5); P=0.03). Systolic blood pressure, arterial compliance, and left ventricular properties were not different. Although heart-to-femoral pulse wave velocity was not different, heart-to-brachial pulse wave velocity tended to be faster in previous preeclamptics (374±8 versus 404±20 cm/s; P=0.06). Stress-induced increase in forearm blood flow was less in previous preeclamptics (245%±21% versus 136%±22%; P=0.01), indicating impaired endothelial function. No significant differences were observed in markers of endothelial activation, dyslipidemia, or oxidative stress; previous preeclamptics tended to have higher glucose level (58.7±1.9 versus 95±5.2 mg/dL; P=0.06). Logistic regression analysis indicated that a simultaneous evaluation of multiple derived indices better discriminated between the 2 groups. The differences in the previous preeclamptic group are in directions known to be associated with greater cardiovascular disease risk later in life. PMID: 21606389 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Serum Myostatin Levels and Grip Strength in Normal Subjects and Patients on Maintenance Haemodialysis. Clin Endocrinol (Oxf). 2011 May 23; Authors: Han DS, Chen YM, Lin SY, Chang HH, Huang TM, Chi YC, Yang WS Objective: Myostatin, a negative regulator of skeletal muscle growth, may modulate grip strength, an indicator of muscle function. Its serum levels could be modulated by maintenance haemodialysis (MHD). Design: A descriptive cross-sectional study. Patients: Forty-one normal controls and 60 MHD patients using different dialyzers at a medical centre. Measurements: The grip strength of the dominant hand, body composition, and the pre-dialysis and post-dialysis serum myostatin and IGF-1 levels were measured. Results: The MHD patients had lower body mass index, IGF-1 level, and grip strength than the normal controls. The patients using the high-flux dialyzer had better grip strength than those using the low-flux (25.5 vs. 19.2 kg). The pre-dialysis myostatin level was higher in low-flux dialyzer than high-flux (31.0 vs. 18.5 ug/ml). Interestingly, the high-flux dialyzer reduced the serum myostatin by 36%, whereas low-flux dialyzer increased it by 25%. The myostatin was inversely related to age and the use of high-flux dialyzer. Furthermore, the grip strength was negatively related to age, female gender, muscle mass, myostatin levels and haemodialysis, but positively to the use of high-flux dialyzer in linear regression. The risk of low grip strength was 7.6 times higher in those with higher serum myostatin with the adjustment of age, gender, muscle mass, haemodialysis and mode of dialysis in a logistic regression. Conclusions: The mode of dialyzer modulates the blood levels of myostatin. Higher myostatin is associated with lower muscle function. The use of myostatin assay in various clinical settings merits further investigation. PMID: 21605155 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human Muscle Proteome Modifications Following Acute or Repeated Eccentric Exercises. Med Sci Sports Exerc. 2011 May 20; Authors: Hody S, Leprince P, Sergeant K, Renaut J, Croisier JL, Wang F, Rogister B INTRODUCTION:: DOMS (Delayed-Onset Muscle Soreness), a condition triggered by eccentric exercise, affects muscle cells at a biochemical level in a poorly understood fashion. The objective of the present study was to examine human muscle proteome modifications induced by strenuous eccentric exercises following a specific training aimed to prevent DOMS. METHODS:: Biopsy of the rectus femoris were taken from healthy human volunteers in three successive conditions: (1) at rest, (2) 24 hours after an injuring exercise protocol consisting of 3 series of 30 maximal contractions of the quadriceps on an isokinetic dynamometer, (3) 24 hours after a similar exercise bout preceded either by 5 eccentric training sessions, or no training. RESULTS:: Muscle damage was assessed before and 1 day after each maximal eccentric test by comparing three indirect markers: plasma activity of creatine kinase (CK), muscle stiffness and subjective pain intensity. Compared to the first eccentric test, those markers were reduced after the second test and further reduced if this second test followed the eccentric training, thus confirming the protective effect of such training. Muscle protein extracts were subjected to a 2D-DIGE proteomic analysis coupled with MALDI-TOF-MS protein identification. Surprisingly, we observed that myosin heavy chains decreased after the first eccentric test, and were reduced further with other contractile proteins after the second test. Furthermore, the expression of several glycolytic enzymes decreased only after the second test that was preceded by a specific training. CONCLUSION:: These findings suggest that the eccentric training resulted in a switch to oxidative metabolism, which may be associated with protection from DOMS. PMID: 21606878 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Development of Histocompatible Primate Induced Pluripotent Stem Cells for Neural Transplantation. Stem Cells. 2011 May 23; Authors: Deleidi M, Hargus G, Hallett P, Osborn T, Isacson O Immune rejection and risk of tumor formation are perhaps the greatest hurdles in the field of stem cell transplantation. Here, we report the generation of several lines of induced pluripotent stem cells (iPSCs) from Cynomolgus macaque (CM) skin fibroblasts carrying specific major histocompatibility complex (MHC) haplotypes. In order to develop a collection of MHC-matched iPSCs, we genotyped the MHC locus of 25 CM by microsatellite PCR analysis. Using retroviral infection of dermal skin fibroblasts, we generated several CM-iPSC lines carrying different haplotypes. We characterized the immunological properties of CM-iPSCs and demonstrated that CM-iPSCs can be induced to differentiate in vitro along specific neuronal populations, such as midbrain dopaminergic (DA) neurons. Midbrain-like DA neurons generated from CM-iPSCs integrated into the striatum of a rodent model of Parkinson's disease (PD) and promoted behavioral recovery. Importantly, neither tumor formation nor inflammatory reactions were observed in the transplanted animals up to six months after transplantation. We believe that the generation and characterization of such histocompatible iPSCs will allow the pre-clinical validation of safety and efficacy of iPSCs for neurodegenerative diseases and several other human conditions in the field of regenerative medicine. PMID: 21608081 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mitochondria: A sulfhydryl oxidase and fission GTPase connect mitochondrial dynamics with pluripotency in embryonic stem cells. Int J Biochem Cell Biol. 2011 May 13; Authors: Wilkerson DC, Sankar U Mitochondria have long been recognized as cellular energy power houses that also regulate cellular redox signaling to arbitrate cell survival. Recent studies of mitochondria in stem cells (SCs) demonstrate that they have critical roles beyond this traditional view. Embryonic (E) SCs, termed pluripotent for their ability to differentiate into all cell types within an organism, maintain a limited number of morphologically undifferentiated (electron translucent and poorly formed cristae) mitochondria. As these cells differentiate, their mitochondria undergo a tightly choreographed gain of number, mass and morphological complexity. Therefore, mechanisms that regulate mitochondrial growth, localization, division and partition must play active roles in the maintenance of pluripotency and execution of differentiation. Aberrant mitochondrial dynamics are associated with a plethora of human disorders, for which SCs hold curative potential. Hence, a comprehensive understanding of the mechanisms that regulate mitochondrial dynamics and function in SCs and their overall relationship to the maintenance of pluripotency is pivotal for the progression of therapeutic regenerative medicine. PMID: 21605695 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | ES cell-derived renewable and functional midbrain dopaminergic progenitors. Proc Natl Acad Sci U S A. 2011 May 23; Authors: Chung S, Moon JI, Leung A, Aldrich D, Lukianov S, Kitayama Y, Park S, Li Y, Bolshakov VY, Lamonerie T, Kim KS During early development, midbrain dopaminergic (mDA) neuronal progenitors (NPs) arise from the ventral mesencephalic area by the combined actions of secreted factors and their downstream transcription factors. These mDA NPs proliferate, migrate to their final destinations, and develop into mature mDA neurons in the substantia nigra and the ventral tegmental area. Here, we show that such authentic mDA NPs can be efficiently isolated from differentiated ES cells (ESCs) using a FACS method combining two markers, Otx2 and Corin. Purified Otx2(+)Corin(+) cells coexpressed other mDA NP markers, including FoxA2, Lmx1b, and Glast. Using optimized culture conditions, these mDA NPs continuously proliferated up to 4 wk with almost 1,000-fold expansion without significant changes in their phenotype. Furthermore, upon differentiation, Otx2(+)Corin(+) cells efficiently generated mDA neurons, as evidenced by coexpression of mDA neuronal markers (e.g., TH, Pitx3, Nurr1, and Lmx1b) and physiological functions (e.g., efficient DA secretion and uptake). Notably, these mDA NPs differentiated into a relatively homogenous DA population with few serotonergic neurons. When transplanted into PD model animals, aphakia mice, and 6-OHDA-lesioned rats, mDA NPs differentiated into mDA neurons in vivo and generated well-integrated DA grafts, resulting in significant improvement in motor dysfunctions without tumor formation. Furthermore, grafted Otx2(+)Corin(+) cells exhibited significant migratory function in the host striatum, reaching >3.3 mm length in the entire striatum. We propose that functional and expandable mDA NPs can be efficiently isolated by this unique strategy and will serve as useful tools in regenerative medicine, bioassay, and drug screening. PMID: 21606375 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human pluripotent stem cells: From biology to cell therapy. World J Stem Cells. 2010 Apr 26;2(2):24-33 Authors: Ramirez JM, Bai Q, Dijon-Grinand M, Assou S, Gerbal-Chaloin S, Hamamah S, Vos JD Human pluripotent stem cells (PSCs), encompassing embryonic stem cells and induced pluripotent stem cells, proliferate extensively and differentiate into virtually any desired cell type. PSCs endow regenerative medicine with an unlimited source of replacement cells suitable for human therapy. Several hurdles must be carefully addressed in PSC research before these theoretical possibilities are translated into clinical applications. These obstacles are: (1) cell proliferation; (2) cell differentiation; (3) genetic integrity; (4) allogenicity; and (5) ethical issues. We discuss these issues and underline the fact that the answers to these questions lie in a better understanding of the biology of PSCs. To contribute to this aim, we have developed a free online expression atlas, Amazonia!, that displays for each human gene a virtual northern blot for PSC samples and adult tissues (http://www.amazonia.transcriptome.eu). PMID: 21607113 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stromal cells from human perinatal tissues: From biology to cell therapy. World J Stem Cells. 2010 Aug 26;2(4):81-92 Authors: Bieback K, Brinkmann I Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop innovative therapeutics for organ failure. Utilizing stem and progenitor cells for organ replacement has been conducted for many years when performing hematopoietic stem cell transplantation. Since the first successful transplantation of umbilical cord blood to treat hematological malignancies, non-hematopoietic stem and progenitor cell populations have recently been identified within umbilical cord blood and other perinatal and fetal tissues. A cell population entitled mesenchymal stromal cells (MSCs) emerged as one of the most intensely studied as it subsumes a variety of capacities: MSCs can differentiate into various subtypes of the mesodermal lineage, they secrete a large array of trophic factors suitable of recruiting endogenous repair processes and they are immunomodulatory.Focusing on perinatal tissues to isolate MSCs, we will discuss some of the challenges associated with these cell types concentrating on concepts of isolation and expansion, the comparison with cells derived from other tissue sources, regarding phenotype and differentiation capacity and finally their therapeutic potential. PMID: 21607124 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering a novel three-dimensional contractile myocardial patch with cell sheets and decellularised matrix. Eur J Cardiothorac Surg. 2010 Oct;38(4):450-5 Authors: Hata H, Bär A, Dorfman S, Vukadinovic Z, Sawa Y, Haverich A, Hilfiker A A persistent problem in generating a functional myocardial patch is maintaining contractions in a thicker construct. Thus far, we have successfully created contracting constructs with a defined directionality by seeding neonatal rat cardiomyocytes (CMs) on decellularised porcine small-intestinal submucosa (SIS). Here, we report our efforts in generating a thicker contracting construct by combining CM cell sheets with CM-seeded SIS. PMID: 20335044 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Plasma-micropatterning of albumin nanoparticles: Substrates for enhanced cell-interactive display of ligands. Biointerphases. 2010 Dec;5(4):105-13 Authors: Rossi MP, Xu J, Schwarzbauer J, Moghe PV The authors demonstrate a novel, efficient, and widely applicable approach to direct the patterning of ligand-functionalized organic nanoparticles derived from albumin on nonconductive, biodegradable polymeric substrates. In contrast to traditional deposition methods for inorganic nanoparticles, the approach involves oxygen plasma treatment of spatially restricted regions on a nonbiopermissive polymer. Albumin nanoparticles conjugated with a truncated fragment of fibronectin containing the Arg-Gly-Asp domain were successfully patterned and used as templates to elicit adhesion and spreading of human mesenchymal stem cells and fibroblasts. Attachment and spreading of both cell types into the plasma-exposed polymer areas was considerably more pronounced than with the ligand alone. The authors hypothesize that the underlying mechanism is oxygen plasma treatment-induced selective enhancement of ligand exposure from the deposited functionalized nanoparticles, which facilitates ligand receptor clustering at the cell membrane. The results highlight a promising nanoscale approach to modulate ligand presentation and spatially direct cell attachment and phenotypic behaviors. PMID: 21219031 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A novel strategy for engineering vascularized grafts in vitro. World J Stem Cells. 2010 Aug 26;2(4):93-6 Authors: Liu JC Tissue engineering is an interdisciplinary field promising new therapeutic means for replacing lost or severely damaged tissues or organs. However, the fabrication of complex engineered tissues has been hampered due to the lack of vascularization to provide sufficient blood supply after implantation. In this article, we propose using rapid prototyping technology to prefabricate a scaffold with an inside hollowed vascular system including an arterial end, a venous end and capillary networks between them. The scaffold will be ''printed'' layer by layer. When printing every layer, a ''low-melting point'' material will be used to form a blood vessel network and a tissue-specific material will be used outside it. Hereafter the 'low-melting point' material will be evacuated by vaporization to ensure a hollowed vessel network. Then the inside hollowed capillary network can be endothelialized by using autologous endothelial cells in a cycling bioreactor while the outside material can be embedded with tissue-special cells. In the end, the new vascularized autologous grafts could be transferred to the defect site by using microsurgical techniques to connect the grafts with the host artery and vein. The strategy would facilitate construction of complex tissue engineering if the hypothesis proved to be practical. PMID: 21607125 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Label-Free Protein Profiling of Adipose-Derived Human Stem Cells under Hyperosmotic Treatment. J Proteome Res. 2011 May 23; Authors: Oswald ES, Brown LM, Bulinski JC, Hung C Our previous work suggested that treatment of cells with hyperosmotic media during 2D passaging primes cells for cartilage tissue engineering applications. Here, we used label-free proteomic profiling to evaluate the effects of control and hyperosmotic treatment environments on the phenotype of multipotent adipose-derived stem cells (ASCs) cultivated with a chondrogenic growth factor cocktail. Spectra were recorded in a data-independent fashion at alternate low (precursor) and high (product) fragmentation voltages (MS<sup>E</sup>). This method was supplemented with data mining of accurate mass and retention time matches in precursor ion spectra across the experiment. The results indicated a complex cellular response to osmotic treatment, with a number of proteins differentially expressed between control and treated cell groups. The roles of some of these proteins have been documented in the literature as characteristic of the physiological states studied, especially aldose reductase (osmotic stress). This protein acted as a positive control in this work, providing independent corroborative validation. Other proteins, including 5'-nucleotidase and transgelin, have been previously linked to cell differentiation state. This study demonstrates that label-free profiling can serve as a useful tool in characterizing cellular responses to chondrogenic treatment regimes, recommending its use in optimization of cell priming protocols for cartilage tissue engineering. PMID: 21604804 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Progress and application prospect of pig induced pluripotent stem cells]. Yi Chuan. 2011 Apr;33(4):307-13 Authors: Yan YB, Zhang YL, Qi WW, Wan YJ, Fan YX, Wang F Pig has always been the focus of establishing a big ungulate animal ES cell lines because of its convenient source, genetic similarity with humans, and their importance in animal husbandry, but little development is achieved. Induced pluripotent stem cells technology creates a new method of reprogramming somatic cells to pluripotent state. As the pig iPS cells is established and perfected, pig ES cells will be established in the coming years. The pig iPS cells will give a hint on other livestock ES cells. On the other hand, pig iPS cells can be used to improve the efficiency of transgenic cloning pigs to conduct effective breeding and conservation of breeds. It is particularly important that the pig iPS cells can provide new model for human medical research, a new donor cells for human tissue and organ engineering, and have extensive and far-reaching impact on the biomedical field. Here, we briefly review the major progress of iPS cells, and emphasize current state of pig iPS cells and its application prospect in biomedicine and animal husbandry in order to provide a useful reference for researchers working in this area. PMID: 21482519 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions: technique note and an early stability pilot clinical trial. Injury. 2010 Jul;41(7):693-701 Authors: Kon E, Delcogliano M, Filardo G, Pressato D, Busacca M, Grigolo B, Desando G, Marcacci M Osteochondral articular defects are a key concern in orthopaedic surgery. Current surgical techniques to repair osteochondral defects lead to poor subchondral bone regeneration and fibrocartilage formation, which is often associated with joint pain and stiffness. The objective of this pilot clinical study is to evaluate the performance and the intrinsic stability of a newly developed biomimetic osteochondral scaffold and to test the safety and the feasibility of the surgical procedure. PMID: 20035935 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Experimental research progress of warming yang and reinforcing kidney of Chinese medicine to promote the differentiation of bone marrow stromal cells]. Zhongguo Gu Shang. 2011 Apr;24(4):352-6 Authors: Chen WH, Wang HM Bone marrow stromal cells (BMSCs), a kind of stem cells residing in bone marrow, have self-renewal, high proliferative capacity and the potential of multilineage differentiation. It has a good prospect in application of the cell replacement therapy, the gene therapy and the tissue engineering and so on. As the content of BMSCs is extremely low in bone marrow, BM-SCs must be amplified in vitro and induced to differentiation to meet the clinical needs. Researches of the recent years suggest there is a very promising way that Chinese medicine could induce BMSCs proliferation, differentiation. Based on the Chinese medicine theory, "the kidney generating marrow and dominating bone" and "kidney storing essence, essence and marrow", the TCM scholars have done some researches to explore the function of warming yang and reinforcing kidney of Chinese medicine to promote bone marrow stromal cells and found that these drugs can promote the BMSCs to proliferate and to differentiate into osteogenic, cartilage and nerve cells. This article elaborates and presents the researches on this aspect. PMID: 21604541 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Comparison of different tissue-derived stem cell sheets for periodontal regeneration in a canine 1-wall defect model. Biomaterials. 2011 May 21; Authors: Tsumanuma Y, Iwata T, Washio K, Yoshida T, Yamada A, Takagi R, Ohno T, Lin K, Yamato M, Ishikawa I, Okano T, Izumi Y Cytotherapeutic approaches have been investigated to overcome the limitations of existing procedures for periodontal regeneration. In this study, cell sheet transplantation was performed using three kinds of mesenchymal tissue (periodontal ligament, alveolar periosteum, and bone marrow)-derived cells to compare the differences between cell sources in a canine severe defect model (one-wall intrabony defect). Periodontal ligament cells (PDLCs), iliac bone marrow mesenchymal stromal cells (BMMSCs), and alveolar periosteal cells (APCs) were obtained from each dog; a total of four dogs were used. Three-layered cell sheets of each cell source supported with woven polyglycolic acid were autologously transplanted to the denuded root surface. One-wall intrabony defects were filled with a mixture of β-tricalcium phosphate (β-TCP) and collagen. Eight weeks after the transplantation, periodontal regeneration was significantly observed with both newly formed cementum and well-oriented PDL fibers more in the PDLC group than in the other groups. In addition, nerve filament was observed in the regenerated PDL tissue only in the PDLC group. The amount of alveolar bone regeneration was highest in the PDLC group, although it did not reach statistical significance among the groups. These results indicate that PDLC sheets combined with β-TCP/collagen scaffold serve as a promising tool for periodontal regeneration. PMID: 21605900 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | RGD-conjugated copolymer incorporated into composite of poly(lactide-co-glycotide) and poly(L-lactide)-grafted nano-hydroxyapatite for bone tissue engineering. Biomacromolecules. 2011 May 23; Authors: Zhang P, Wu H, Wu H, Lù Z, Deng C, Hong Z, Jing X, Chen X Various surface modification methods of RGD (Arg-Gly-Asp) peptides on biomaterials have been developed to improve cell adhesion. This study aimed to examine a RGD conjugated copolymer RGD/MPEG-PLA-PBLG (RGD-copolymer) for its ability to promote bone regeneration by mixing it with the composite of poly(lactide-co-glycotide) (PLGA) and hydroxyapatite nanoparticles surface-grafted with poly(L-lactide) (g-HAP). The porous scaffolds were prepared using solvent casting/particulate leaching method and grafted to repair the rabbit radius defects after seeding with autologous MSCs of rabbits. After incorporation of RGD-copolymer, there were no significant influences on scaffold's porosity and pore size. Nitrogen of RGD peptide, and calcium and phosphor of g-HAP could be exposed on the surface of the scaffold simultaneously. Although the cell viability of its leaching liquid was 92% that was lower than g-HAP/PLGA, its cell adhesion and growth of 3T3 and osteoblasts were promoted significantly. All the defects repaired with the implants were bridged after 24 weeks post-surgery but RGD-copolymer contained composite had larger new bone formation and better fusion interface. The composites containing RGD-copolymer enhanced bone ingrowth but presented more woven bones than others. The combined application of RGD-copolymer and bone morphological protein 2 (BMP-2) exhibited the best bone healing quality. PMID: 21604718 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Comparison of six bone-graft substitutes regarding to cell seeding efficiency, metabolism and growth behaviour of human mesenchymal stem cells (MSC) in vitro. Injury. 2010 Jul;41(7):731-8 Authors: Seebach C, Schultheiss J, Wilhelm K, Frank J, Henrich D Various synthetic bone-graft substitutes are used commercially as osteoconductive scaffolds in the treatment of bone defects and fractures. The role of bone-graft substitutes is changing from osteoconductive conduits for growth to an delivery system for biologic fracture treatments. Achieving optimal bone regeneration requires biologics (e.g. MSC) and using the correct scaffold incorporated into a local environment for bone regeneration. The need for an unlimited supply with high quality bone-graft substitutes continue to find alternatives for bone replacement surgery. PMID: 20233614 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival. Pediatr Surg Int. 2011 Feb;27(2):137-43 Authors: Miyasaka EA, Raghavan S, Gilmont RR, Mittal K, Somara S, Bitar KN, Teitelbaum DH Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality. PMID: 21046117 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The structural and biological properties of hydroxyapatite-modified titanate nanowire scaffolds. Biomaterials. 2011 May 21; Authors: Zhao H, Dong W, Zheng Y, Liu A, Yao J, Li C, Tang W, Chen B, Wang G, Shi Z Hydroxyapatite-modified titanate nanowire scaffolds as alternative materials for tissue engineering have been developed via a titanate nanowire matrix assisted electrochemical deposition method. The macroporous titanate nanowire matrix on Ti metal was fabricated by a hydrothermal method, and then followed by an electrochemical synthesis of hydroxyapatite nanoparticles on titanate nanowire. The incorporation of titanate nanowire matrix with high oriented hydroxyapatite nanoparticles generates hierarchical scaffolds with highly osteogenic, structural integrity and excellent mechanical performance. As-prepared porous three dimensional interconnected hydroxyapatite-modified titanate nanowire scaffolds, mimicking the nature's extracellular matrix, could provide a suitable microenvironment for tissue cell ingrowth and differentiation. The ceramic titanate nanowire core with HA nanoparticle sheath structure displays superhydrophilicity, which facilitates the cell attachment and proliferation, and induces the in vitro tissue-engineered bone. Human osteoblast-like MG63 cells were cultured on the hydroxyapatite-modified titanate nanowire scaffolds, and the results showed that the scaffolds highly promote the bioactivity, osteoconductivity and osteoblast differentiation. PMID: 21605896 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Implantation of polymer scaffolds seeded with neural stem cells in a canine spinal cord injury model. Cytotherapy. 2010 Oct;12(6):841-5 Authors: Kim BG, Kang YM, Phi JH, Kim YH, Hwang DH, Choi JY, Ryu S, Elastal AE, Paek SH, Wang KC, Lee SH, Kim SU, Yoon BW Combinatorial approaches employing diverse therapeutic modalities are required for clinically relevant repair of injured spinal cord in human patients. Before translation into the clinic, the feasibility and therapeutic potential of such combinatorial strategies in larger animal species need to be examined. PMID: 20629485 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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