Wednesday, March 10, 2010

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Murky Backdrop on $5.4 Million Grant to Burnham Scientist
March 10, 2010 at 9:45 PM

Directors of the California stem cell agency tomorrow will be asked to approve a $1.85 million increase in a grant to a Southern California researcher after he filed a proposal that violated CIRM's rules against spending CIRM funds out of state.

The CIRM staff made the recommendation for the 50 percent boost (for a total of $5.4 million) in the grant to Evan Snyder of the Sanford-Burnham
 

Text of Simpson Comment on Snyder Grant
March 10, 2010 at 9:45 PM

Here is the text of the statement from John M. Simpson, stem cell project director for Consumer Watchdog of Santa Monica, Ca., concerning the Evan Snyder grant.

"Either the applicant deliberately flouted the rules requiring all research
to be done in California and thought he could get away with it or he didn't
understand the rules. In either case he did not follow them.

"Assume the best and,
 

Text of Snyder Comment on his CIRM Grant
March 10, 2010 at 9:45 PM

Here is the text of Evan Snyder's response to a request for comments involving his CIRM grant.

"Actually, contrary to Mr. Simpson's assertions, this project uses the funds of California's taxpayer's -- particularly those who suffer from Parkinson's Disease and other neurodegenerative diseases -- in the most economical and frugal manner possible. The only authentic model of Parkinson's Disease
 

CIRM on Snyder Grant
March 10, 2010 at 9:44 PM

Here is additional information from Don Gibbons, chief communications officer from CIRM, on the Evan Snyder grant.

"The budget for the California researcher included a research subcontract to
a US organization outside California.  CIRM followed standard practice for
this funding round, performing a detailed budget review of each proposal
approved by the Board.  When it became clear that this
 

Seaweed extract may hold promise for non-Hodgkin's lymphoma treatment
March 10, 2010 at 9:42 PM

 

Stem Cell Therapeutics Corp. Announces Publication of Phase IIa Stroke Data
March 10, 2010 at 3:59 PM

 

Correction and More Details on Snyder Grant
March 10, 2010 at 3:32 PM

The California stem cell agency says the out-of-state work planned by Evan Snyder of the Sanford/Burnham Institute in his $3.6 million grant was scheduled for another party elsewhere in the United States – not Australia.

We reported incorrectly yesterday that the matter involved work in Victoria. CIRM posted documents about the matter for its board of directors meeting tomorrow, but did not name
 

Novel stroke treatment passes safety stage of UCI-led clinical trial
March 10, 2010 at 1:58 PM

 

Molecule tells key brain cells to grow up, get to work, Stanford study shows
March 10, 2010 at 1:58 PM

 

ImmunoCellular Therapeutics' Dendritic Cell-Based Vaccine Demonstrates Statistically Significant Increase in Survival in an Animal Model of Glioblastoma
March 10, 2010 at 8:57 AM

 

Entest BioMedical Strengthens Its Research Capabilities by Adding Clinical Trials Expert Dr. Vladimir Bogin to Its Scientific Advisory Board
March 10, 2010 at 8:57 AM

 

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction.
March 10, 2010 at 8:07 AM

Related Articles

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction.

Am J Cardiol. 2010 Mar 15;105(6):804-812

Authors: Wöhrle J, Merkle N, Mailänder V, Nusser T, Schauwecker P, von Scheidt F, Schwarz K, Bommer M, Wiesneth M, Schrezenmeier H, Hombach V

To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42! patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 x 10(6) mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 +/- 6.4% versus -0.9 +/- 5.5% at 1 month, 3.1 +/- 6.0% versus 1.9 +/- 4.3% at 3 months, and 5.7 +/- 8.4% versus 1.8 +/- 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.

PMID: 20211323 [PubMed - as supplied by publisher]

 

In vitro human bone marrow analog: clinical potential.
March 10, 2010 at 8:07 AM

Related Articles

In vitro human bone marrow analog: clinical potential.

Regen Med. 2010 Mar;5(2):289-98

Authors: Nichols JE, Niles J, Walls S, Cortiella J

Bone marrow is the primary site of hematopoiesis in adult humans. Bone marrow can be cultured in vitro but few simple culture systems fully support hematopoiesis beyond a few months. Human bone marrow analogs are long-term in vitro cultures of marrow stromal and hematopoietic stem cells that can be used to produce cells and products normally harvested from human donors. Bone marrow analog systems should exhibit confluence of the stromal cell populations, persistence of hematopoietic progenitor cells, presence of active regions of hematopoiesis and capacity to produce mature cell types for extended periods of time. Although we are still years away from realizing clinical application of products formed by artificial bone marrow analogs, the process of transitioning this research tool from bench to bedside should be fairly straightforward. The most obvious application of artificial marrow would be for production of autologous hematopoietic CD34(+) stem cells as a ste! m cell therapy for individuals experiencing bone marrow failure due to disease or injury. Another logical application is for 'blood farming', a process for large-scale in vitro production of red blood cells, white blood cells or platelets, for transfusion or treatment. Other possibilities include production of nonhematopoietic stem cells such as osteogenic stromal cells, osteoblasts and rare pluripotent stem cells. Bone marrow analogs also have great potential as ex vivo human test systems and could play a critical role in drug discovery, drug development and toxicity testing in the future.

PMID: 20210588 [PubMed - in process]

 

Epidermis grafting: from adult to embryonic stem cells.
March 10, 2010 at 8:07 AM

Related Articles

Epidermis grafting: from adult to embryonic stem cells.

Regen Med. 2010 Mar;5(2):157-9

Authors: Peschanski M, Lemaitre G, Nissan X, Baldeschi C

PMID: 20210574 [PubMed - in process]

 

High Throughput Screening 2010 Study Finds HTS Laboratories Using Effective Screening Strategies and Innovative Technologies to Increase Drug Discovery Success
March 10, 2010 at 7:57 AM

 

SnapShot: Bioreactors systems in tissue engineering (TE) & regenerative medicine (RM).
March 10, 2010 at 7:11 AM

Related Articles

SnapShot: Bioreactors systems in tissue engineering (TE) & regenerative medicine (RM).

Biomaterials. 2010 Apr;31(11):3114-5

Authors: Martin I, Riboldi SA, Jakob M, Wendt D

PMID: 20213922 [PubMed - in process]

 

Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: From fabrication to preclinical validation.
March 10, 2010 at 7:11 AM

Related Articles

Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: From fabrication to preclinical validation.

J Biomed Mater Res A. 2010 Mar 8;

Authors: Mondalek FG, Ashley RA, Roth CC, Kibar Y, Shakir N, Ihnat MA, Fung KM, Grady BP, Kropp BP, Lin HK

Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane angiogenesis model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-! PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

PMID: 20213816 [PubMed - as supplied by publisher]

 

Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation.
March 10, 2010 at 7:11 AM

Related Articles

Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation.

J Biomed Mater Res A. 2010 Mar 8;

Authors: Carpenedo RL, Seaman SA, McDevitt TC

Differentiation of pluripotent embryonic stem cells (ESCs) in vitro via multicellular spheroids called embryoid bodies (EBs) is commonly performed to model aspects of early mammalian development and initiate differentiation of cells for regenerative medicine technologies. However, the three-dimensional nature of EBs poses unique challenges for directed ESC differentiation, including limited diffusion into EBs of morphogenic molecules capable of specifying cell fate. Degradable polymer microspheres incorporated within EBs can present morphogenic molecules to ESCs in a spatiotemporally controlled manner to more efficiently direct differentiation. In this study, the effect of microsphere size on incorporation into EBs and ESC differentiation in response to microsphere- mediated morphogen delivery were assessed. PLGA microspheres with mean diameters of 1, 3, or 11 mum were fabricated and mixed with ESCs during EB formation. Smaller microspheres were incorporated more ! efficiently throughout EBs than larger microspheres, and regardless of size, retained for at least 10 days of differentiation. Retinoic acid release from incorporated microspheres induced EB cavitation in a size-dependent manner, with smaller microspheres triggering accelerated and more complete cavitation than larger particles. These results demonstrate that engineering the size of microsphere delivery vehicles incorporated within stem cell environments can be used to modulate the course of differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

PMID: 20213812 [PubMed - as supplied by publisher]

 

Editorial comment.
March 10, 2010 at 7:11 AM

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Editorial comment.

Urology. 2010 Mar;75(3):670

Authors: Atala A

PMID: 20211376 [PubMed - in process]

 

Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells.
March 10, 2010 at 7:11 AM

Related Articles

Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells.

Exp Cell Res. 2010 Mar 5;

Authors: Terrace JD, Hay DC, Samuel K, Anderson RA, Currie IS, Parks RW, Forbes SJ, Ross JA

Future treatments for chronic liver disease are likely to involve manipulation of liver progenitor cells (LPCs). In the human, data characterising the regenerative response is limited and the origin of adult LPCs is unknown. However, these remain critical factors in the design of cell-based liver therapies. The developing human liver provides an ideal model to study cell lineage derivation from progenitors and to understand how foetal haematopoiesis and liver development might explain the nature of the adult LPC population. In 1st trimester human liver, portal venous endothelium (PVE) expressed adult LPC markers and markers of haematopoietic progenitor cells (HPCs) shared with haemogenic endothelium found in the embryonic dorsal aorta. Sorted PVE cells were able to generate hepatoblast-like cells co-expressing CK18 and CK19 in addition to Dlk/pref-1, E-cadherin, albumin and fibrinogen in vitro. Furthermore, PVE cells could initiate haematopoiesis. These data sugge! st that PVE shares phenotypical and functional similarities both with adult LPCs and embryonic haemogenic endothelium. This indicates that a temporal relationship might exist between progenitor cells in foetal liver development and adult liver regeneration, which may involve progeny of PVE.

PMID: 20211168 [PubMed - as supplied by publisher]

 

FGF but not EGF induces phosphorylation of the cAMP response element binding protein in olfactory mucosa-derived cell cultures.
March 10, 2010 at 7:11 AM

Related Articles

FGF but not EGF induces phosphorylation of the cAMP response element binding protein in olfactory mucosa-derived cell cultures.

Exp Cell Res. 2010 Mar 5;

Authors: Barraud P, He X, Zhao C, Caldwell MA, Franklin RJ

The stem/progenitor cells of the olfactory epithelium are potentially useful cells for autologous cell-based therapy because of their relative accessibility compared to other sources of neural stem cells. However, they have very limited potential to self-renew in vitro under growth factor stimulation compared to central nervous system-derived stem/progenitor cells. Using a sphere-forming assay and immunocytochemistry to identify cells that contained phosphorylated cAMP response element binding protein (pCREB) as an indicator of cell responsiveness to growth factor activation, we found that olfactory-spheres primed with FGF2 responded to FGF2 and EGF stimulation. In contrast, olfactory-spheres primed with EGF failed to respond to FGF2 or EGF stimulation despite the detection of FGFR1 and EGFR and their transcripts. These data demonstrate that FGF2 but not EGF permit the maintenance of a subset of cells responsive to FGF2 and EGF whereas EGF induces unresponsive to ! either growth factor possibly via intrinsic mechanisms of regulation.

PMID: 20211167 [PubMed - as supplied by publisher]

 

Regulation of cell shape, wing hair initiation and the actin cytoskeleton by Trc/Fry and Wts/Mats complexes.
March 10, 2010 at 7:11 AM

Related Articles

Regulation of cell shape, wing hair initiation and the actin cytoskeleton by Trc/Fry and Wts/Mats complexes.

Dev Biol. 2010 Mar 5;

Authors: Fang X, Adler PN

The two NDR kinase family genes in Drosophila are tricornered (trc) and warts (wts). Previous studies on trc have focused on its role in the morphogenesis of extensions of epidermal cells and in dendrite branching and tiling. Studies on wts have focused on its roles as a tumor suppressor, in controlling photoreceptor type and in the maintenance of dendrites. Here we examine and compare the function of these genes in wing cells prior to their terminal differentiation. Mutations in these genes lead to changes in cell shape, cellular levels of F-actin, the timing of differentiation, and the expression of multiple wing hairs and DE-Cadherin. We showed that the effects of wts on all of these processes appear to be mediated by its regulation of the Yorkie transcription factor. We also provide evidence that trc regulates the expression of DE-cadherin and mwh. In addition, we showed that the effects on cell shape and the timing of differentiation appear to not be linked t! o changes in relative growth rate of cells compared to their neighbors.

PMID: 20211163 [PubMed - as supplied by publisher]

 

Acknowledgements.
March 10, 2010 at 7:11 AM

Related Articles

Acknowledgements.

Regen Med. 2010 Mar;5(2):305

Authors:

PMID: 20210589 [PubMed - in process]

 

In vitro human bone marrow analog: clinical potential.
March 10, 2010 at 7:11 AM

Related Articles

In vitro human bone marrow analog: clinical potential.

Regen Med. 2010 Mar;5(2):289-98

Authors: Nichols JE, Niles J, Walls S, Cortiella J

Bone marrow is the primary site of hematopoiesis in adult humans. Bone marrow can be cultured in vitro but few simple culture systems fully support hematopoiesis beyond a few months. Human bone marrow analogs are long-term in vitro cultures of marrow stromal and hematopoietic stem cells that can be used to produce cells and products normally harvested from human donors. Bone marrow analog systems should exhibit confluence of the stromal cell populations, persistence of hematopoietic progenitor cells, presence of active regions of hematopoiesis and capacity to produce mature cell types for extended periods of time. Although we are still years away from realizing clinical application of products formed by artificial bone marrow analogs, the process of transitioning this research tool from bench to bedside should be fairly straightforward. The most obvious application of artificial marrow would be for production of autologous hematopoietic CD34(+) stem cells as a ste! m cell therapy for individuals experiencing bone marrow failure due to disease or injury. Another logical application is for 'blood farming', a process for large-scale in vitro production of red blood cells, white blood cells or platelets, for transfusion or treatment. Other possibilities include production of nonhematopoietic stem cells such as osteogenic stromal cells, osteoblasts and rare pluripotent stem cells. Bone marrow analogs also have great potential as ex vivo human test systems and could play a critical role in drug discovery, drug development and toxicity testing in the future.

PMID: 20210588 [PubMed - in process]

 

Autobionics: a new paradigm in regenerative medicine and surgery.
March 10, 2010 at 7:11 AM

Related Articles

Autobionics: a new paradigm in regenerative medicine and surgery.

Regen Med. 2010 Mar;5(2):279-88

Authors: Ashrafian H, Darzi A, Athanasiou T

The concept of bionics was developed 50 years ago and represented the development of engineering and technology based on natural biological systems. Traditional applications of bionics in healthcare include artificial bionic organs that apply engineering principles to replace or augment physiological functions by integrating electronic, mechanical or electromechanical components to inherent body tissues/organs (we term this as 'exobionics'). Recently, there has been a new wave of bio-inspired treatments that act through the reorganization of the existing biological organs in an individual to enhance physiology. Here, the technology does not replace biological tissue, but rather applies engineering principles to replace or augment physiological functions by the rearrangement and manipulation of inherent tissue/organs; we term this autobionics. Examples include: dynamic cardiomyoplasty (artificial heart pump using skeletal muscle), the Ross procedure (pulmonary auto! graft), dynamic graciloplasty (artificial sphincter) and metabolic gastric bypass (rearranging the gastrointestinal tract to modify gut- and pancreatic-hormone release). Autobionic therapies can be classified into dynamic, static and metabolic procedures. This results in tissue redesignation (one tissue used in place of another), tissue replacement and systems reorganization (rearranging inherent organ/tissue anatomy). In some cases autobionic procedures can enhance physiological function beyond normality and represents a new era in bio-inspired versatility.

PMID: 20210587 [PubMed - in process]

 

Stem cell-derived dopamine neurons for brain repair in Parkinson's disease.
March 10, 2010 at 7:11 AM

Related Articles

Stem cell-derived dopamine neurons for brain repair in Parkinson's disease.

Regen Med. 2010 Mar;5(2):267-78

Authors: Fricker-Gates RA, Gates MA

One of the prospects for a curative treatment for Parkinson's disease is to replace the lost dopaminergic neurons. Preclinical and clinical trials have demonstrated that dissected fetal dopaminergic neurons have the potential to markedly improve motor function in animal models and Parkinson's disease patients. However, this source of cells will never be sufficient to use as a widespread therapy. Over the last 20 years, scientists have been searching for other reliable sources of midbrain dopamine neurons, and stem cells appear to be strong candidates. This article reviews the potential of different types of stem cells, from embryonic to adult to induced pluripotent stem cells, to see how well the cells can be differentiated into fully functional dopamine neurons, which cells might be the best candidates and how much more research is required before stem cell technology might be translated to a clinical therapy for Parkinson's disease.

PMID: 20210586 [PubMed - in process]

 

Efficient isolation and chondrogenic differentiation of adult mesenchymal stem cells with fibrin microbeads and micronized collagen sponges.
March 10, 2010 at 7:11 AM

Related Articles

Efficient isolation and chondrogenic differentiation of adult mesenchymal stem cells with fibrin microbeads and micronized collagen sponges.

Regen Med. 2010 Mar;5(2):255-65

Authors: Shainer R, Gaberman E, Levdansky L, Gorodetsky R

Background: Mesenchymal stem cells (MSCs) have been demonstrated to potentially undergo chondrogenic differentiation. We propose a new matrix for stem cell-based chondrogenesis using dense fibrin microbeads (FMBs) combined with grounded dehydrothermally crosslinked collagen sponges (micronized collagen). Methods: In this study, MSCs were isolated from bone marrow of transgenic green fluorescent protein C57/Bl mice by FMBs in high yield. After 48 h in slowly rotating suspension culture, micronized collagen was added. Results: The cells on the FMBs migrated to the collagen pieces and formed aggregates that developed into cartilage-like structures. Following chondrogenic differentiation, alcian blue staining and collagen type II immunohistochemistry demonstrated the presence of chondrocytes in the 3D structures. PCR for the expression of aggrecan and collagen type II genes supported these findings. The in vitro structures that formed were used for ectopic subdermal i! mplantation in wild-type C57/Bl mice. However, the chondrogenic markers faded relative to the pre-implant in vitro structures. Conclusion: We propose that FMBs with micronized collagen could serve as a simple technology for MSC isolation and chondrogenesis as a basis for implantation.

PMID: 20210585 [PubMed - in process]

 

Control of in vitro neural differentiation of mesenchymal stem cells in 3D macroporous, cellulosic hydrogels.
March 10, 2010 at 7:11 AM

Related Articles

Control of in vitro neural differentiation of mesenchymal stem cells in 3D macroporous, cellulosic hydrogels.

Regen Med. 2010 Mar;5(2):245-53

Authors: Gu H, Yue Z, Leong WS, Nugraha B, Tan LP

Background: Mesenchymal stem cells (MSCs) are multipotent cells that can be induced to differentiate into multiple cell lineages, including neural cells. They are a good cell source for neural tissue-engineering applications. Cultivation of human (h)MSCs in 3D scaffolds is an effective means for the development of novel neural tissue-engineered constructs, and may serve as a promising strategy in the treatment of nerve injury. Aim: This study presents the in vitro growth and neural differentiation of hMSCs in 3D macroporous, cellulosic hydrogels. Results: The number of hMSCs cultivated in the 3D scaffolds increased by more than 14-fold after 7 days. After 2 days induction, most of the hMSCs in the 3D scaffolds were positive for nestin, a marker of neural stem cells. After 7 days induction, most of the hMSCs in the 3D scaffolds showed glial fibrillary acidic protein, tubulin or neurofilament M-positive reaction and a few hMSCs were positive for nestin. After 14 day! s induction, hMSCs in the 3D scaffolds could completely differentiate into neurons and glial cells. The neural differentiation of hMSCs in the 3D scaffolds was further demonstrated by real-time PCR. Conclusion: These results show that the 3D macroporous cellulosic hydrogel could be an appropriate substrate for neural differentiation of hMSCs and its possible applications in neural tissue engineering are discussed.

PMID: 20210584 [PubMed - in process]

 

Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133(+) endothelial progenitor cells for cardiac repair.
March 10, 2010 at 7:11 AM

Related Articles

Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133(+) endothelial progenitor cells for cardiac repair.

Regen Med. 2010 Mar;5(2):231-44

Authors: Rufaihah AJ, Haider HK, Heng BC, Ye L, Tan RS, Toh WS, Tian XF, Sim EK, Cao T

Objective: This study aim to enhance endothelial differentiation of human embryonic stem cells (hESCs) by transduction of an adenovirus (Ad) vector expressing hVEGF(165) gene (Ad-hVEGF(165) ). Purified hESC-derived CD133(+) endothelial progenitors were transplanted into a rat myocardial infarct model to assess their ability to contribute to heart regeneration. Methods: Optimal transduction efficiency with high cell viability was achieved by exposing differentiating hESCs to viral particles at a ratio of 1:500 for 4 h on three consecutive days. Results: Reverse transcription-PCR analysis showed positive upregulation of VEGF, Ang-1, Flt-1, Tie-2, CD34, CD31, CD133 and Flk-1 gene expression in Ad-hVEGF(165) -transduced cells. Additionally, flow cytometric analysis of CD133, a cell surface marker, revealed an approximately fivefold increase of CD133 marker expression in Ad-hVEGF(165) -transduced cells compared with the nontransduced control. Within a rat myocardial in! farct model, transplanted CD133(+) endothelial progenitor cells survived and participated, both actively and passively, in the regeneration of the infarcted myocardium, as seen by an approximately threefold increase in mature blood vessel density (13.62 +/- 1.56 vs 5.11 +/- 1.23; p < 0.01), as well as significantly reduced infarct size (28% +/- 8.2% vs 76% +/- 5.6%; p < 0.01) in the transplanted group compared with the culture medium-injected control. There was significant improvement in heart function 6 weeks post-transplantation, as confirmed by regional blood-flow analysis (1.72 +/- 0.612 ml/min/g vs 0.8 +/- 0.256 ml/min/g; p < 0.05), as well as echocardiography assessment of left ventricular ejection fraction (60.855% +/- 7.7% vs 38.22 +/- 8.6%; p < 0.05) and fractional shortening (38.63% +/- 9.3% vs 25.2% +/- 7.11%; p < 0.05). Conclusion: hESC-derived CD133(+) endothelial progenitor cells can be utilized to regenerate the infarcted heart.

PMID: 20210583 [PubMed - in process]

 

In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.
March 10, 2010 at 7:11 AM

Related Articles

In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.

Regen Med. 2010 Mar;5(2):221-9

Authors: Prasad Nayak B, Hong Goh JC, Toh SL, Satpathy GR

Background: Entheses are fibrocartilaginous organs that bridge ligament with bone at their interface and add significant insertional strength. To replace a severely damaged ligament, a tissue-engineered graft preinstalled with interfacial fibrocartilage, which is being regenerated from stem cells, appears to be more promising than ligament-alone graft. Such a concept can be realized by a biomimetic approach of establishing a dynamic communication of stem cells with bone cells and/or ligament fibroblasts in vitro. Aim: The current study has two objectives. The first objective is to demonstrate functional coculture of bone marrow-derived stem cells (BMSCs) with mature bone cells/ligament fibroblasts as evidenced by gap-junctional communication in vitro. The second objective is to investigate the role of BMSCs in the regeneration of fibrocartilage within the coculture. Materials & methods: Rabbit bone/ligament fibroblasts were dual-stained with DiI-Red and calcei! n (gap-junction permeable dye), and cocultured with unlabeled BMSCs at fixed ratio (1:10). The functional gap junction was demonstrated by the transfer of calcein from donor to recipient cells that was confirmed and quantified by flow cytometry. Type 2 collagen (cartilage extracellular matrix-specific protein) expressed by the mixed cell lines in the cocultures were estimated by real-time reverse transcription PCR and compared with that of the ligament-bone coculture (control). Results: Significant transfer of calcein into BMSCs was observed and flow cytometry analyses showed a gradual increase in the percentage of BMSCs acquiring calcein with time. Cocultures that included BMSCs expressed significantly more type 2 collagen compared with the control. Conclusion: The current study, for the first time, reported the expression of gap-junctional communication of BMSCs with two adherent cell lines of musculoskeletal system in vitro and also confirmed that incorporation of stem c! ells augments fibrocartilage regeneration. The results open up! a path to envisage a composite graft preinstalled with enthesial fibrocartilage using a stem cell-based coculture system.

PMID: 20210582 [PubMed - in process]

 

The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.
March 10, 2010 at 7:11 AM

Related Articles

The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.

Regen Med. 2010 Mar;5(2):201-20

Authors: Wang G, Badylak SF, Heber-Katz E, Braunhut SJ, Gudas LJ

Method: We injected two drugs that modify the epigenome, the DNA methyltransferase inhibitor 5-aza-2 -deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA), alone or in combination, into C57Bl/6 mice subjected to amputation through the mid-second phalanx of the third digit. Wound-site tissue was collected. Results: We observed increased staining of the stem cell markers Rex1 (Zfp42) and stem cell antigen-1 at digit amputation sites from drug-treated mice. Samples from 5-aza-dC plus TSA and TSA treated mice also showed increased proliferating cell nuclear antigen staining, a measure of cell proliferation. Drug treatments increased Msx1, but not Cyp26a1 or ALDH1a2 (RALDH2) mRNA. Conclusion: 5-aza-dC and TSA treatments stimulated cell proliferation at the amputation site, possibly via increased expression of genes involved in digit development and regeneration.

PMID: 20210581 [PubMed - in process]

 

Conference Scene: Emerging themes in the stem cells space.
March 10, 2010 at 7:11 AM

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Conference Scene: Emerging themes in the stem cells space.

Regen Med. 2010 Mar;5(2):197-200

Authors: Razvi ES

The focus of this article is to present and highlight some selected topics and emerging trends from this excellent annual conference hosted by Select Biosciences Ltd. at the Embassy Suites San Francisco Airport Hotel, CA, USA. This conference attracted a worldwide audience of more than 100 delegates representing a number of different areas - basic researchers involved with stem cells, representatives from pharmaceutical, biotechnology and vendor companies, a diverse array of industry participants from the stem cell therapeutics space, as well as stem cell clinics from around the world. The scope of industry coverage presented at this conference included stem cells in cellular therapy and regenerative medicine, pluripotency/induced pluripotent stem cells, and stem cells for drug discovery and development. These categories represented the major themes into which the bulk of the presentations at this conference were organized. The major thrust of this conference was ! on the application of stem cells for cellular therapy - in this regard, it is important to note that mesenchymal stem cells are the most promising types of adult stem cells for regenerative medicine and cellular therapy. Many presentations at this conference were focused around mesenchymal stem cells for cellular therapy in a number of different disease areas.

PMID: 20210580 [PubMed - in process]

 

Company Profile: Biocompatibles International plc: local drug delivery for targeted therapies.
March 10, 2010 at 7:11 AM

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Company Profile: Biocompatibles International plc: local drug delivery for targeted therapies.

Regen Med. 2010 Mar;5(2):189-95

Authors: Coppen D

Biocompatibles International plc is focused on the development of targeted therapies for a range of indications, including oncology, neurology and cardiology. By delivering the therapy directly to the site of a localized disease numerous benefits can be achieved, including the targeting of a very high therapeutic dose to the required location and reduced systemic toxicity. As part of this strategy the company is now a leader in the field of using locally placed stem cells to make and deliver therapeutically active peptide drugs. The encapsulated cells (CellBeads((R))), modified to produce a potent anti-apoptotic peptide, CM1, are currently being evaluated in a Phase I/IIa study for the treatment of stroke and in preclinical models of acute myocardial infarction.

PMID: 20210579 [PubMed - in process]

 

Company Profile: Tissue regeneration for diabetes and neurological diseases at Living Cell Technologies.
March 10, 2010 at 7:11 AM

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Company Profile: Tissue regeneration for diabetes and neurological diseases at Living Cell Technologies.

Regen Med. 2010 Mar;5(2):181-7

Authors: Tan PLj

Living Cell Technologies' (LCT's) cell-based therapeutic for Type 1 diabetes, DIABECELL((R)), comprises encapsulated porcine insulin-producing cells. DIABECELL is presently in a Phase II clinical trial in New Zealand following positive early results. The cells are implanted into the abdomen to replace the patient's pancreatic beta-islet cells that have been lost as a result of autoimmune disease. LCT is also developing brain choroid plexus cells for the treatment of neurologic diseases. The aim is to enhance the brain's natural repair mechanism by implanting cells releasing neurotrophins. Choroid plexus cell implants alleviate disease in animal models of Parkinson's disease, Huntington's disease and stroke. LCT encapsulates all cells in alginate, permitting implantation without using immunosuppressive drugs.

PMID: 20210578 [PubMed - in process]

 

Research highlights.
March 10, 2010 at 7:11 AM

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Research highlights.

Regen Med. 2010 Mar;5(2):175-9

Authors: Kerstetter AE, Miller RH

PMID: 20210577 [PubMed - in process]

 

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