|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | The California stem cell agency has awarded $32 million to researchers to help them devise technology to overcome obstacles to development of stem cell therapies, part of $41 mllion in spending approved today.
In approving 19 tools and technology grants, CIRM directors rejected four appeals of negative recommendations from reviewers. That included a petition by Stanford researcher Stefan Heller | | | | | | | | | | | | | | | | | | | | | | | | | The meeting of the directors of the California stem cell agency concluded about an hour ago. We will have a story coming shortly on action on various grant and spending proposals. | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency today embarked on a fresh course for selection of a new chairman of the $3 billion effort, including a self-evaluation of the performance of the agency board itself.
On a unanimous voice vote, the governing board initiated a survey of its 29 directors to determine criteria that they believe is desirable in a new chairman, in addition to the legal | | | | | | | | | | | | | | | | | | | | | | | | | The CIRM board resumed discussions about 1 p.m. PST. | | | | | | | | | | | | | | | | | | | | | | | | | CIRM directors have been in an executive session since about 11:18 p.m PST. They are discussing personnel issues and proprietary information concerning the $40 million tools and technology grant round. It is not clear when they will resume their public session. | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency today decided to post their statements of economic interest on the CIRM web site along with those of the executives of the $3 billion enterprise. Also to be posted will be the expense claims filed by the same officials.
The action was approved on a unanimous voice vote. It came at the request of Citizens Financial Accountability Oversight Committee ( | | | | | | | | | | | | | | | | | | | | | | | | | A novel method for the isolation of subpopulations of rat adipose stem cells with different proliferation and osteogenic differentiation potentials. J Tissue Eng Regen Med. 2011 Jan 26; Authors: Rada T, Gomes ME, Reis RL Bone marrow has been the elected cell source of studies published so far concerning bone and cartilage tissue-engineering approaches. Recent studies indicate that adipose tissue presents significant advantages over bone marrow as a cell source for tissue engineering. Most of these studies report the use of adipose stem cells (ASCs) isolated by a method based on the enzymatic digestion of the adipose tissue and on the ability of stem cells to adhere to a cell culture plastic surface. Using this method, a heterogeneous population was obtained containing different cell types that have been shown to compromise the proliferation and differentiation potential of the stem cells. This paper reports the development and optimization of a new isolation method that enables purified cell populations to be obtained that exhibit higher osteogenic differentiation and/or proliferation potential. This method is based on the use of immunomagnetic beads coated with specific antibodies and it is compared with other methods described in the literature for the selection of stem cell populations, e.g. methods based on a gradient solution and enzymatic digestion. The results showed that the isolation method based on immunomagnetic beads allows distinct subpopulations of rat ASCs to be isolated, showing different stem cells marker expressions and different osteogenic differentiation potentials. Therefore, this method can be used to study niches in ASC populations and/or also allow adipose tissue to be used as a stem cell source in a more efficient manner, increasing the potential of this cell source in future clinical applications. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21268288 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hydrostatic pressure independently increases elastin and collagen co-expression in small-diameter engineered arterial constructs. J Biomed Mater Res A. 2011 Jan 25; Authors: Crapo PM, Wang Y Prior studies have demonstrated that smooth muscle cell (SMC) proliferation, migration, and extracellular matrix production increase with hydrostatic pressure in vitro. We have engineered highly compliant small-diameter arterial constructs by culturing primary adult baboon arterial SMCs under pulsatile perfusion on tubular, porous, elastomeric scaffolds composed of poly(glycerol sebacate) (PGS). This study investigates the effect of hydrostatic pressure on the biological and mechanical properties of PGS-based engineered arterial constructs. Pressure was raised using a downstream needle valve during perfusion while preserving flow rate and pulsatility, and constructs were evaluated by pressure-diameter testing and biochemical assays for collagen and elastin. Pressurized constructs contained half as much insoluble elastin as baboon common carotid arteries but were significantly less compliant, while constructs cultured at low hydrostatic pressure contained one-third as much insoluble elastin as baboon carotids and were similar in compliance. Hydrostatic pressure significantly increased construct burst pressure, collagen and insoluble elastin content, and soluble elastin concentration in culture medium. All arteries and constructs exhibited elastic recovery during pressure cycling. Hydrostatic pressure did not appear to affect radial distribution of SMCs, collagens I and III, and elastin. These results provide insights into the control of engineered smooth muscle tissue properties using hydrostatic pressure. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21268239 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem and progenitor cells for neurological repair: Minor issues, major hurdles, and exciting opportunities for paracrine-based therapeutics. J Cell Biochem. 2011 Feb;112(2):374-380 Authors: Shimada IS, Spees JL The transplantation of cultured stem and progenitor cells is a key element in the rapidly growing field of regenerative medicine. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have already entered into clinical trials. However, despite several decades of intense research, the goal to apply culture-expanded stem/progenitor cells in a manner that can effectively replace cells after injury has yet to be realized. Many sources of potentially useful cells are available, but something is clearly missing. In addition, recent studies suggest that paracrine effects of secreted or released factors are responsible for most of the benefits observed after cell transplantation, rather than direct cell replacement. These data call into question the need for cell transplantation for many types of therapy, in particular for acute injuries such as myocardial infarction and stroke. In this review, we examine current progress in the area of cell transplantation and minor issues and major hurdles regarding the clinical application of different cell types. We discuss the "paracrine hypothesis" for the action of transplanted stem/progenitor cells as an opportunity to identify defined combinations of biomolecules to rescue and/or repair tissues after injury. Although many of the concepts in this review will apply to multiple injury/repair systems, we will focus primarily on stem/progenitor cell-based treatments for neurological disorders and stroke. J. Cell. Biochem. 112: 374-380, 2011. © 2010 Wiley-Liss, Inc. PMID: 21268056 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells. Nat Commun. 2011 Jan;2:167 Authors: Tsutsui H, Valamehr B, Hindoyan A, Qiao R, Ding X, Guo S, Witte ON, Liu X, Ho CM, Wu H A major challenge in stem cell-mediated regenerative medicine is the development of defined culture systems for the maintenance of clinical-grade human embryonic stem (hES) cells. Here, we identify, using a feedback system control scheme, a unique combination of three small molecule inhibitors that enables the maintenance of hES cells on a fibronectin-coated surface through single cell passaging. After 20 passages, the undifferentiated state of the hES cells was confirmed by OCT4, SSEA4 and NANOG expressions, whereas their pluripotent potential and genetic integrity were demonstrated by teratoma formation and normal karyotype, respectively. Our study attests to the power of the feedback system control scheme to quickly pinpoint optimal conditions for desired biological activities, and provides a chemically defined, scalable and single cell passaging culture system for hES cells. PMID: 21266967 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Native human adipose stromal cells: localization, morphology and phenotype. Int J Obes (Lond). 2011 Jan 25; Authors: Maumus M, Peyrafitte JA, D'Angelo R, Fournier-Wirth C, Bouloumié A, Casteilla L, Sengenès C, Bourin P Objectives:Beside having roles in energy homeostasis and endocrine modulation, adipose tissue (AT) is now considered a promising source of mesenchymal stromal cells (adipose-derived stromal cells or ASCs) for regenerative medicine. Despite numerous studies on cultured ASCs, native human ASCs are rarely investigated. Indeed, the phenotype of ASCs in their native state, their localization within AT and comparison with bone marrow-derived mesenchymal stromal cells (BM-MSCs) has been poorly investigated.Design:To address these issues, the stroma vascular fraction (SVF) of human AT was extracted and native cell subtypes were isolated by immunoselection to study their clonogenic potential in culture. Immunohistology on samples of human AT in combination with reconstruction of confocal sections were performed in order to localize ASCs.Results:Compared with BM-MNCs, all native ASCs were found in the CD34(+) cell fraction of the AT-SVF. Native ASCs expressed classical mesenchymal markers described for BM-MSCs. Interestingly, CD34 expression decreased during ASC cell culture and was negatively correlated with cell proliferation rate. Immunohistological analysis revealed that native ASCs exhibited specific morphological features with protrusions. They were found scattered in AT stroma and did not express in vivo pericytic markers such as NG2, CD140b or alpha-smooth muscle actin, which appeared during the culture process. Finally, ASCs spontaneous commitment to adipocytic lineage was enhanced in AT from obese humans.Conclusions:The use of complementary methodological approaches to study native human ASCs revealed their immunophenotype, their specific morphology, their location within AT and their stemness. Furthermore, our data strongly suggest that human ASCs participate in adipogenesis during AT development.International Journal of Obesity advance online publication, 25 January 2011; doi:10.1038/ijo.2010.269. PMID: 21266947 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | Some CIRM grant reviewers have filed a minority report on a tools-and-technology grant rejected by the agency's grant reviewers. The application was submitted by a business. The biotech industry has complained about the paucity of CIRM grants to business. The review summary said,
"Three elements were cited by the minority group in support of moving the application up to Tier 1: 1) the | | | | | | | | | | | | | | | | | | | | | | | | A fifth scientist has filed an appeal of a negative decision by CIRM's scientific reviewers on his application for $1.2 million in the $40 million tools and technology round.
The researcher is Alexander Urban of Stanford University, the third scientist from that institution whose application was rejected. Here is the summary of the reviewers findings. | | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell opened their meeting this morning in Burlingame at 11:17 a.m. PST with introduction of two new members of the 29-member board and a new alternate for a regular member. The first order of business is the $40 million tools and technology round of grants. The board has a quorum but Chairman Klein warned that some directors will have to leave early -- not an | | | | | | | | | | | | | | | | | | | | | | | | | The California Stem Cell Report will be providing live coverage of today's meeting of the board of the California stem cell agency from our location in El Salvador. The meeting has not yet begun but it is likely to get underway soon. We will file reports as warranted throughout the day based on the Internet broadcast of the proceedings. | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency today released a glowing report on its economic impact that was produced by a firm that was charged by CIRM with executing "a vibrant and aggressive strategy to support the goals and initiatives of CIRM."
The agency's press release on the $300,000, 25-page study said that CIRM's spending will generate 25,000 "job years" and $200 million in new tax revenue by the | | | | | | | | | | | | | | | | | | | | | | | | | A novel method for the isolation of subpopulations of rat adipose stem cells with different proliferation and osteogenic differentiation potentials. J Tissue Eng Regen Med. 2011 Jan 26; Authors: Rada T, Gomes ME, Reis RL Bone marrow has been the elected cell source of studies published so far concerning bone and cartilage tissue-engineering approaches. Recent studies indicate that adipose tissue presents significant advantages over bone marrow as a cell source for tissue engineering. Most of these studies report the use of adipose stem cells (ASCs) isolated by a method based on the enzymatic digestion of the adipose tissue and on the ability of stem cells to adhere to a cell culture plastic surface. Using this method, a heterogeneous population was obtained containing different cell types that have been shown to compromise the proliferation and differentiation potential of the stem cells. This paper reports the development and optimization of a new isolation method that enables purified cell populations to be obtained that exhibit higher osteogenic differentiation and/or proliferation potential. This method is based on the use of immunomagnetic beads coated with specific antibodies and it is compared with other methods described in the literature for the selection of stem cell populations, e.g. methods based on a gradient solution and enzymatic digestion. The results showed that the isolation method based on immunomagnetic beads allows distinct subpopulations of rat ASCs to be isolated, showing different stem cells marker expressions and different osteogenic differentiation potentials. Therefore, this method can be used to study niches in ASC populations and/or also allow adipose tissue to be used as a stem cell source in a more efficient manner, increasing the potential of this cell source in future clinical applications. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21268288 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Temporal progression of the host response to implanted poly(ethylene glycol)-based hydrogels. J Biomed Mater Res A. 2011 Jan 25; Authors: Lynn AD, Blakney AK, Kyriakides TR, Bryant SJ Poly(ethylene glycol) (PEG) hydrogels hold great promise as in vivo cell carriers for tissue engineering. To ensure appropriate performance of these materials when implanted, the host response must be well understood. The objectives for this study were to characterize the temporal evolution of the foreign body reaction (FBR) to acellular PEG-based hydrogels prepared from PEG diacrylate precursors when implanted subcutaneously in immunocompentent c57bl/6 mice by (immuno)histochemical analysis and gene expression. Compared with a normal FBR elicited by silicone (SIL), PEG hydrogels without or with a cell adhesion ligand RGD elicited a strong early inflammatory response evidenced by a thick band of macrophages as early as day 2, persisting through two weeks, and by increased interleukin-1β expression. PEG-only hydrogels showed a slower, but more sustained progression of inflammation over PEG-RGD. Temporal changes in gene expression were observed in response to PEG-based materials and in general exhibited, elevated expression of inflammatory and wound healing genes in the tissues surrounding the implants, while the expression patterns were more stable in response to SIL. While a stabilized FBR was achieved with SIL and to a lesser degree with PEG-RGD, the PEG-only hydrogels had not yet stabilized after 4 weeks. In summary, PEG-only hydrogels elicit a strong early inflammatory reaction, which persists throughout the course of the implantation even as a collagenous capsule begins to form. However, the incorporation of RGD tethers partially attenuates this response within 2 weeks leading to an improved FBR to PEG-based hydrogels. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. PMID: 21268236 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of three-dimensional culture and incubator gas concentration on phenotype and differentiation capability of human mesenchymal stem cells. J Cell Biochem. 2011 Feb;112(2):684-693 Authors: Karlsen TA, Mirtaheri P, Shahdadfar A, Fløisand Y, Brinchmann JE To obtain sufficient numbers of cells for tissue engineering applications, human bone marrow-derived mesenchymal stem cells (hBM-MSC) are commonly cultured as monolayers in incubators containing room air. In this study, we investigated whether three-dimensional (3D) culture conditions and incubator gas concentrations more similar to those observed in vivo impacted on cell expansion, differentiation capability, or phenotype of hBM-MSC. We found that 3D culture alone increased the expression of some molecules involved in osteogenic and adipogenic differentiation. In contrast, 3D culture did not induce chondrogenic differentiation, but enhanced the response to the chondrogenic differentiation medium. Changing the oxygen concentration to 6% and the carbon dioxide concentration to 7.5% did not impact on the results of any of our assays, showing that the hyperoxia of room air is not detrimental to hBM-MSC proliferation, differentiation, or phenotype. J. Cell. Biochem. 112: 684-693, 2011. © 2010 Wiley-Liss, Inc. PMID: 21268090 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency last night belatedly gave the public its first glimpse at a $200,000 plan to subsidize attendance at an international stem cell conference in Toronto in June.
A one-sentence version of the proposal has been on the agenda of the directors of the California stem cell agenda for 10 days. However, the cost, number of persons involved and other details were not | | | | | | | | | | | | | | | | | | | | | | | | | A novel method for the isolation of subpopulations of rat adipose stem cells with different proliferation and osteogenic differentiation potentials. J Tissue Eng Regen Med. 2011 Jan 26; Authors: Rada T, Gomes ME, Reis RL Bone marrow has been the elected cell source of studies published so far concerning bone and cartilage tissue-engineering approaches. Recent studies indicate that adipose tissue presents significant advantages over bone marrow as a cell source for tissue engineering. Most of these studies report the use of adipose stem cells (ASCs) isolated by a method based on the enzymatic digestion of the adipose tissue and on the ability of stem cells to adhere to a cell culture plastic surface. Using this method, a heterogeneous population was obtained containing different cell types that have been shown to compromise the proliferation and differentiation potential of the stem cells. This paper reports the development and optimization of a new isolation method that enables purified cell populations to be obtained that exhibit higher osteogenic differentiation and/or proliferation potential. This method is based on the use of immunomagnetic beads coated with specific antibodies and it is compared with other methods described in the literature for the selection of stem cell populations, e.g. methods based on a gradient solution and enzymatic digestion. The results showed that the isolation method based on immunomagnetic beads allows distinct subpopulations of rat ASCs to be isolated, showing different stem cells marker expressions and different osteogenic differentiation potentials. Therefore, this method can be used to study niches in ASC populations and/or also allow adipose tissue to be used as a stem cell source in a more efficient manner, increasing the potential of this cell source in future clinical applications. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21268288 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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