|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency this week opened the door to a broader and more open way of determining who should lead the $3 billion enterprise for the next six years.
They set in motion a process in which the directors will publicly establish criteria that they would like to see in a person who would succeed Robert Klein as chairman come next June. No details were forthcoming | | | | | | | | | | | | | | | | | | | | | | | | | Amniotic fluid as a source of pluripotent and multipotent stem cells for organ regeneration. Curr Opin Organ Transplant. 2010 Dec 13; Authors: Da Sacco S, De Filippo RE, Perin L PURPOSE OF REVIEW: Amniotic fluid, due to its contact to the fetus during development, is considered an important diagnostic tool to evaluate the health status of the fetus during pregnancy. However, amniotic fluid also contains a heterogeneous cellular population that can be safely collected by amniocentesis and easily cultured. Many different cell types have been found within amniotic fluid and currently some of them are being tested for their possible use for cellular therapy. RECENT FINDINGS: Potential of pluripotent and multipotent cells isolated from the amniotic fluid has been tested and in-vitro differentiations toward various cell types have been successfully performed. Furthermore, in-vivo studies are highlighting the benefits and mechanisms of amniotic fluid cells for therapy, with particular focus on kidney and lung diseases. SUMMARY: Amniotic fluid may represent a precious source for easily and safely retrievable cell types that may be used for regenerative medicine purposes. PMID: 21157345 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Enteric nervous system neuropathy: repair and restoration. Curr Opin Gastroenterol. 2010 Dec 13; Authors: Wood JD PURPOSE OF REVIEW: Disordered neurobiology of the enteric nervous system (ENS) underlies a broad assortment of idiopathic, acquired, and congenital pathophysiologies up and down the digestive tract. Progress in two major areas of regenerative medicine related to enteric neuropathy is summarized: new insight into how everyday damage to the ENS might be corrected by indwelling stem cells and prospects for patient-specific replacement of damaged or diseased intestine with one reproduced from pluripotent stem cells derived from embryos or reprogramed adult cells. RECENT FINDINGS: Germinal centers with undifferentiated stem cells are in position outside ENS ganglia. Messages, which might be released after damage to the ENS or when neurons are lost, direct migration of stem cells into ENS ganglia where they differentiate into one or the other of the specialized classes of interneurons or motor neurons and become 'wired' into the synaptic circuits as neuronal replacements. Action of serotonin and the 5-hydroxytryptamine (HT)4 receptor subtype is a message that initiates the neuronal replacement and circuit restoration process. A reasonable facsimile of a functional intestine can be derived from pluripotent stem cells. SUMMARY: Emerging knowledge of cell and molecular biology of indwelling stem cells in the gut and strategies for application of pluripotential stem cells in patient-specific organ transplantation reflect an emergent revolution in understanding and treating disordered gut function when the underlying cause is ENS neuropathy. PMID: 21157326 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder. BJU Int. 2010 Oct;106(8):1114-27 Authors: Andersson KE, Gratzke C, Hedlund P • The pathophysiology of lower urinary tract symptoms (LUTS), detrusor overactivity (DO), and the overactive bladder (OAB) syndrome is multifactorial and remains poorly understood. • The transient receptor potential (TRP) channel superfamily has been shown to be involved in nociception and mechanosensory transduction in various organ systems, and studies of the LUT have indicated that several TRP channels, including TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1, are expressed in the bladder, and may act as sensors of stretch and/or chemical irritation. • However, the roles of these individual channels for normal LUT function and in LUTS/DO/OAB, have not been established. • TRPV1 is the channel best investigated. It is widely distributed in LUT structures, but despite extensive information on morphology and function in animal models, the role of this channel in normal human bladder function is still controversial. Conversely, its role in the pathophysiology and treatment of particularly neurogenic DO is well established. • TRPV1 is co-expressed with TRPA1, and TRPA1 is known to be present on capsaicin-sensitive primary sensory neurones. Activation of this channel can induce DO in animal models. • TRPV4 is a Ca(2+)-permeable stretch-activated cation channel, involved in stretch-induced ATP release, and TRPV4-deficient mice exhibit abnormal frequencies of voiding and non-voiding contractions in cystometric experiments. • TRPM8 is a cool receptor expressed in the urothelium and suburothelial sensory fibres. It has been implicated in the bladder-cooling reflex and in idiopathic DO. • The occurrence of other members of the TRP superfamily in the LUT has been reported, but information on their effects on LUT functions is scarce. There seem to be several links between activation of different members of the TRP superfamily and LUTS/DO/OAB, and further exploration of the involvement of these channels in LUT function, normally and in dysfunction, may be rewarding. PMID: 21156013 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Lectin microarray analysis of pluripotent and multipotent stem cells. Genes Cells. 2010 Dec 13; Authors: Toyoda M, Yamazaki-Inoue M, Itakura Y, Kuno A, Ogawa T, Yamada M, Akutsu H, Takahashi Y, Kanzaki S, Narimatsu H, Hirabayashi J, Umezawa A Stem cells have a capability to self-renew and differentiate into multiple types of cells; specific markers are available to identify particular stem cells for developmental biology research. In this study, we aimed to define the status of somatic stem cells and the pluripotency of human embryonic stem (hES) and induced pluripotent stem (iPS) cells using a novel molecular methodology, lectin microarray analysis. Our lectin microarray analysis successfully categorized murine somatic stem cells into the appropriate groups of differentiation potency. We then classified hES and iPS cells by the same approach. Undifferentiated hES cells were clearly distinguished from differentiated hES cells after embryoid formation. The pair-wise comparison means based on 'false discovery rate' revealed that three lectins -Euonymus europaeus lectin (EEL), Maackia amurensis lectin (MAL) and Phaseolus vulgaris leucoagglutinin [PHA(L)]- generated maximal values to define undifferentiated and differentiated hES cells. Furthermore, to define a pluripotent stem cell state, we generated a discriminant for the undifferentiated state with pluripotency. The discriminant function based on lectin reactivities was highly accurate for judgment of stem cell pluripotency. These results suggest that glycomic analysis of stem cells leads to a novel comprehensive approach for quality control in cell-based therapy and regenerative medicine. PMID: 21155951 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The challenge of regenerative medicine. Hastings Cent Rep. 2010 Nov-Dec;40(6):24-6 Authors: Trommelmans L PMID: 21155108 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Emerging role of epigenetics in stroke: part 1: DNA methylation and chromatin modifications. Arch Neurol. 2010 Nov;67(11):1316-22 Authors: Qureshi IA, Mehler MF Epigenetic mechanisms refer to the complex and interrelated molecular processes that dynamically modulate gene expression and function within every cell in the body. These regulatory systems represent the long-sought-after molecular interfaces that mediate gene × environment interactions. Changes in the epigenome throughout life are responsible not only for controlling normal development, adult homeostasis, and aging but also for mediating responses to injury. Emerging evidence implicates a spectrum of epigenetic processes in the pathophysiology of stroke. In this review, we describe conventional epigenetic mechanisms (including DNA methylation, histone code modifications, nucleosome remodeling, and higher-order chromatin formation) and highlight the emerging roles each of these processes play in the pathobiology of stroke. We suggest that understanding these mechanisms may be important for discovering more sensitive and specific biomarkers for risk, onset, and progression of stroke. In addition, we highlight epigenetic approaches for stroke therapy, including the inhibition of DNA methyltransferase and histone deacetylase enzyme activities. These therapeutic approaches are still in their infancy, but preliminary results suggest that contemporary agents targeting these pathways can regulate the deployment of stress responses that modulate neural cell viability and promote brain repair and functional reorganization. Indeed, these agents even appear to orchestrate sophisticated cognitive functions, including learning and memory. PMID: 21060009 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest. 2010 Sep 1;120(9):3127-36 Authors: Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alexander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J, Semple R, Weber A, Lomas DA, Vallier L Human induced pluripotent stem (iPS) cells hold great promise for advancements in developmental biology, cell-based therapy, and modeling of human disease. Here, we examined the use of human iPS cells for modeling inherited metabolic disorders of the liver. Dermal fibroblasts from patients with various inherited metabolic diseases of the liver were used to generate a library of patient-specific human iPS cell lines. Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions. The resulting cells exhibited properties of mature hepatocytes, such as albumin secretion and cytochrome P450 metabolism. Moreover, cells generated from patients with 3 of the inherited metabolic conditions studied in further detail (alpha1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease type 1a) were found to recapitulate key pathological features of the diseases affecting the patients from which they were derived, such as aggregation of misfolded alpha1-antitrypsin in the endoplasmic reticulum, deficient LDL receptor-mediated cholesterol uptake, and elevated lipid and glycogen accumulation. Therefore, we report a simple and effective platform for hepatocyte generation from patient-specific human iPS cells. These patient-derived hepatocytes demonstrate that it is possible to model diseases whose phenotypes are caused by pathological dysregulation of key processes within adult cells. PMID: 20739751 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model. J Clin Invest. 2010 Sep 1;120(9):3340-9 Authors: Lee CH, Shah B, Moioli EK, Mao JJ Fibroblasts are ubiquitous cells that demonstrate remarkable diversity. However, their origin and pathways of differentiation remain poorly defined. Here, we show that connective tissue growth factor (CTGF; also known as CCN2) is sufficient to induce human bone marrow mesenchymal stem/stromal cells (MSCs) to differentiate into fibroblasts. CTGF-stimulated MSCs lost their surface mesenchymal epitopes, expressed broad fibroblastic hallmarks, and increasingly synthesized collagen type I and tenacin-C. After fibroblastic commitment, the ability of MSCs to differentiate into nonfibroblastic lineages - including osteoblasts, chondrocytes, and adipocytes - was diminished. To address inherent heterogeneity in MSC culture, we established 18 single MSC-derived clones by limiting dilution. CTGF-treated MSCs were alpha-SMA-, differentiating into alpha-SMA+ myofibroblasts only when stimulated subsequently with TGF-beta1, suggestive of stepwise processes of fibroblast commitment, fibrogenesis, and pathological fibrosis. In rats, in vivo microencapsulated delivery of CTGF prompted postnatal connective tissue to undergo fibrogenesis rather than ectopic mineralization. The knowledge that fibroblasts have a mesenchymal origin may enrich our understanding of organ fibrosis, cancer stroma, ectopic mineralization, scarring, and regeneration. PMID: 20679726 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Telocytes accompanying cardiomyocyte in primary culture: two- and three-dimensional culture environment. J Cell Mol Med. 2010 Nov;14(11):2641-5 Authors: Zhou J, Zhang Y, Wen X, Cao J, Li D, Lin Q, Wang H, Liu Z, Duan C, Wu K, Wang C Recently, the presence of telocytes was demonstrated in human and mammalian tissues and organs (digestive and extra-digestive organs, genitourinary organs, heart, placenta, lungs, pleura, striated muscle). Noteworthy, telocytes seem to play a significant role in the normal function and regeneration of myocardium. By cultures of telocytes in two- and three-dimensional environment we aimed to study the typical morphological features as well as functionality of telocytes, which will provide important support to understand their in vivo roles. Neonatal rat cardiomyocytes were isolated and cultured as seeding cells in vitro in two-dimensional environment. Furthermore, engineered myocardium tissue was constructed from isolated cells in three-dimensional collagen/Matrigel scaffolds. The identification of telocytes was performed by using histological and immunohistochemical methods. The results showed that typical telocytes are distributed among cardiomyocytes, connecting them by long telopodes. Telocytes have a typical fusiform cell body with two or three long moniliform telopodes, as main characteristics. The vital methylene blue staining showed the existence of telocytes in primary culture. Immunohistochemistry demonstrated that some c-kit or CD34 immuno-positive cells in engineered heart tissue had the morphology of telocytes, with a typical fusiform cell body and long moniliform telopodes. Also, a significant number of vimentin+ telocytes were present within engineered heart tissue. We suggest that the model of three-dimensional engineered heart tissue could be useful for the ongoing research on the functional relationships of telocytes with cardiomyocytes. Because the heart has the necessary potential of changing the muscle and non-muscle cells during the lifetime, telocytes might play an active role in the heart regeneration process. Moreover, telocytes might be a useful tool for cardiac tissue engineering. PMID: 21158014 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cytocompatibility studies of mouse pancreatic islets on gelatin - PVP semi IPN scaffolds in vitro: Potential implication towards pancreatic tissue engineering. Islets. 2010 Nov 1;2(6) Authors: Muthyala S, Bhonde RR, Nair PD Type 1 diabetes is a chronic disorder that results due to auto immune destruction of insulin producing cells, which leads to hyperglycemia in the blood. The development of an ideal scaffold for maintaining the structure and function of islets is a challenge in the field of pancreatic tissue engineering. In this study, gelatin (G) as well as gelatin / PVP (GP) semi interpenetrating polymer network scaffolds have been fabricated by freeze drying technique and cross linked with gluteraldehyde (GTA) and 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC), which was abbreviated as GG, GPG (cross linked with GTA) GE, and GPE (cross linked with EDC). The presence of gelatin and PVP in GPE and GPG scaffolds was confirmed through FTIR and TGA. The medium uptake ability of GPE and GPG scaffolds were higher than GG and GE scaffolds. The scaffolds were then analyzed for its ability to maintain the viability and function of mouse pancreatic islet cells in vitro. The results showed that the islets can adhere, but it tends to lose the structure and function on all the scaffolds after day 7, except on GPE where they remained intact up to day 30. Thus the present study clearly demonstrates that gelatin incorporated with PVP and cross linked with EDC scaffolds could support and maintain islet cells for prolonged period. PMID: 21157182 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Homing in on a biological joint replacement. Stem Cell Res Ther. 2010 Dec 14;1(5):40 Authors: Guilak F ABSTRACT: The use of tissue engineering therapies for treating damaged articular cartilage has traditionally focused on cell-based therapies for the repair of focal chondral or osteochondral defects. A recent study by Lee and colleagues in the Lancet shows exciting proof-of-concept that an acellular scaffold containing transforming growth factor beta 3 can induce homing of cells that regenerate a hyaline-like cartilage surface. These findings provide a glimpse into the possibility that tissue engineering may in fact provide the means for regeneration of an entire joint surface, beyond a simple focal defect in the articular cartilage. PMID: 21156083 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Basics of tissue engineering and stem cell research. Int J Urol. 2010 Dec;17(12):963 Authors: Baba S PMID: 21155093 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Optimum preservation for autologous cultured dermal substitutes. Ann Plast Surg. 2010 Sep;65(3):338-43 Authors: Hayama Y, Ueda K, Kuroyanagi Y The application of autologous cultured dermal substitute (CDS) is a promising procedure for improving burn scar contracture. Preparation of CDS requires a period of about 3 weeks before the date of surgery. When the date of surgery is postponed, CDS must be preserved under optimum conditions. This study was thus designed to investigate these conditions. CDS was preserved in culture medium for 2 weeks at 37 degrees C, 25 degrees C, or 4 degrees C in dishes sealed with tape. During this period, culture medium was exchanged every week. CDS fibroblast activity was then examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell activity was best retained at 37 degrees C, as compared with the other 2 temperatures. The amount of vascular endothelial growth factor (VEGF) released from CDS was measured by enzyme-linked immunosorbent assay. At 37 degrees C, the amount of VEGF was markedly higher. In contrast, the amount of VEGF decreased at the other 2 temperatures. The results of both MTT assay and enzyme-linked immunosorbent assay indicate that preservation of CDS should be carried out at 37 degrees C. PMID: 20733371 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Three dimensional dental epithelial-mesenchymal constructs of predetermined size and shape for tooth regeneration. Biomaterials. 2010 Nov;31(31):7995-8003 Authors: Zhang W, Ahluwalia IP, Yelick PC While it is known that precise dental epithelial-mesenchymal (DE-DM) cell interactions provide critical functions in tooth development, reliable methods to establish proper DE-DM cell interactions for tooth regeneration have yet to be established. To address this challenge, and to generate bioengineered teeth of predetermined size and shape, in this study, we characterize three dimensional (3D) pre-fabricated DE-DM cell constructs. Human dental pulp cell seeded Collagen gel layers were co-cultured with porcine DE cells suspended in Growth Factor Reduced (GFR) Matrigel. The resulting 3D DE-DM cell layers were cultured in vitro, or implanted and grown subcutaneously in vivo in nude rats. Molecular, histological and immunohistochemical (IHC) analyses of harvested implants revealed organized DE-DM cell interactions, the induced expression of dental tissue-specific markers Amelogenin (AM) and Dentin Sialophosphoprotein (DSPP), and basement membrane markers Laminin 5 and collagen IV, and irregular mineralized tissue formation after 4 weeks. We anticipate that these studies will facilitate the eventual establishment of reliable methods to elaborate dental tissues, and full sized teeth of specified sized and shape. PMID: 20682455 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model. J Clin Invest. 2010 Sep 1;120(9):3340-9 Authors: Lee CH, Shah B, Moioli EK, Mao JJ Fibroblasts are ubiquitous cells that demonstrate remarkable diversity. However, their origin and pathways of differentiation remain poorly defined. Here, we show that connective tissue growth factor (CTGF; also known as CCN2) is sufficient to induce human bone marrow mesenchymal stem/stromal cells (MSCs) to differentiate into fibroblasts. CTGF-stimulated MSCs lost their surface mesenchymal epitopes, expressed broad fibroblastic hallmarks, and increasingly synthesized collagen type I and tenacin-C. After fibroblastic commitment, the ability of MSCs to differentiate into nonfibroblastic lineages - including osteoblasts, chondrocytes, and adipocytes - was diminished. To address inherent heterogeneity in MSC culture, we established 18 single MSC-derived clones by limiting dilution. CTGF-treated MSCs were alpha-SMA-, differentiating into alpha-SMA+ myofibroblasts only when stimulated subsequently with TGF-beta1, suggestive of stepwise processes of fibroblast commitment, fibrogenesis, and pathological fibrosis. In rats, in vivo microencapsulated delivery of CTGF prompted postnatal connective tissue to undergo fibrogenesis rather than ectopic mineralization. The knowledge that fibroblasts have a mesenchymal origin may enrich our understanding of organ fibrosis, cancer stroma, ectopic mineralization, scarring, and regeneration. PMID: 20679726 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Application of tissue-engineered cartilage with BMP-7 gene to repair knee joint cartilage injury in rabbits. Knee Surg Sports Traumatol Arthrosc. 2010 Apr;18(4):496-503 Authors: Che JH, Zhang ZR, Li GZ, Tan WH, Bai XD, Qu FJ Injured articular cartilage has a poor capacity for spontaneous healing. So far, satisfactory solution to this subsistent problem has not been found, but transgenic therapy may be a promising way. This study aims to evaluate the effectiveness of a tissue-engineered cartilage that was transfected with morphogenetic protein 7 (BMP 7) in repairing the cartilaginous defects of rabbit knee joints. Chondrocytes were transfected with BMP-7 gene (5 x 10(6) cells/ml), inoculated into the collagen-fibrin gel scaffolds, and cultured for 14 days. Then, the scaffolds were implanted onto the created defects (5.0 mm in diameter) in rabbits' knee joints. After 12 weeks, the rabbits were sacrificed and histological sections were evaluated using modified O'Driscoll cartilage scores; In situ hybridization and immunohistochemistry were performed to detect the expression of BMP-7 mRNA and BMP-7 at the implanted site while the content of DNA and GAG was determined as well. A better quality of repairs was observed at the 12th week after implantation when compared to the control group using histological analyses. The content of DNA and specific secretion of GAG in the treatment group is statistically significant different compared with the control group. Gene therapy may be a promising treatment method, but the novel therapy approach needs further studies with respect to a longer follow-up period. PMID: 19855958 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | An item today concerning an article on Nature magazine's Web site dealing with the re-election of Robert Klein as chairman of CIRM said that the reporter interviewed Klein yesterday. In fact, Klein was interviewed earlier. | | | | | | | | | | | | | | | | | | | | | | | | Canadian scientist Alan Bernstein is not necessarily off the table as a candidate to become the next chairman of the $3 billion California stem cell agency, Nature magazine's Web site is reporting today.
His name popped up in a piece by Elie Dolgin about the re-election of Bob Klein for a term of six months as chair at the agency as he and the CIRM board search for his replacement.
Dolgin | | | | | | | | | | | | | | | | | | | | | | | | In an item carried Dec. 13 called "Eleven Top Stem Cell Researchers Back Klein for Re-Election," we wrote,
"All but one of them have tens of millions of dollars at stake in grants from the stem cell agency and are heavily invested in basic research, as opposed to translational efforts to push research into the clinic."One of those mentioned by name was Larry Goldstein of UC San Diego, who has | | | | | | | | | | | | | | | | | | | | | | | | One news article on the re-election of Robert Klein as head of the California stem cell agency surfaced quickly tonight with an interesting reminder.
Reporter Ron Leuty's piece in the San Francisco Business Times was straight-forward. But it also refreshed readers on the nomination process for CIRM chair. It noted that two of the next nominees for chair will come from two new state officials, | | | | | | | | | |  | |  | |  |
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