|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Twisting immune responses for allogeneic stem cell therapy. World J Stem Cells. 2009 Dec 31;1(1):30-35 Authors: Li SC, Zhong JF Stem cell-derived tissues and organs have the potential to change modern clinical science. However, rejection of allogeneic grafts by the host's immune system is an issue which needs to be addressed before embryonic stem cell-derived cells or tissues can be used as medicines. Mismatches in human leukocyte class I antigens and minor histocompatibility antigens are the central factors that are responsible for various graft-versus-host diseases. Traditional strategies usually involve suppressing the whole immune systems with drugs. There are many side effects associated with these methods. Here, we discuss an emerging strategy for manipulating the central immune tolerance by naturally "introducing" donor antigens to a host so a recipient can acquire tolerance specifically to the donor cells or tissues. This strategy has two distinct stages. The first stage restores the thymic function of adult patients with sex steroid inhibitory drugs (LHRH-A), keratinocyte growth factor (KGF), interleukin 7 (IL-7) and FMS-like tyrosine kinase 3 (FLT3). The second stage introduces hematopoietic stem cells and their downstream progenitors to the restored thymus by direct injection. Hematopoietic stem cells are used to introduce donor antigens because they have priority access to the thymus. We also review several clinical cases to explain this new strategy. PMID: 20975985 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Intracoronary Autologous CD34+ Stem Cell Therapy for Intractable Angina. Cardiology. 2010 Oct 23;117(2):140-147 Authors: Wang S, Cui J, Peng W, Lu M Background/Objectives: A large number of patients with coronary artery disease experience angina that is not suitable for revascularization and is refractory to conventional medical therapy. Laboratory and preclinical studies have provided evidence for the safety and potential efficacy of autologous CD34+ stem cell therapies as treatment for angina. Clinical studies investigating intramyocardial transplantation of autologous CD34+ stem cells by catheter injection for patients with refractory angina show that this is safe and feasible. It remains unclear whether intracoronary infusion of CD34+ stem cells exerts beneficial effects in patients with angina as well. We addressed this question with a controlled clinical trial by enrolling 112 patients with refractory angina. Previous trials have investigated the safety and beneficial effects of CD34+ cells isolated from granulocyte colony-stimulating factor-mobilized peripheral blood; in our trial, we isolated CD34+ cells directly from the patient's bone marrow. Methods: One hundred and twelve patients with diffuse triple-vessel disease and Canadian Cardiovascular Society class III or IV angina were enrolled in a double-blind, randomized (1:1), placebo-controlled study. Patients received optimal medical treatment but were not candidates for mechanical revascularization (percutaneous coronary intervention or coronary artery bypass grafting). Fifty-six patients (27 women and 29 men aged 42-80 years) were enrolled in the treatment group, and 56 patients (28 women and 28 men aged 43-80 years) who received optimal medical treatment and intracoronary saline injections were enrolled in the placebo control group. Bone marrow was collected from all enrolled patients at a volume of 120-150 ml each in both groups. Selections of CD34+ cells were performed by a CE-marked device approved by the Security, Food and Drug Administration of China. Coronary angiography had been performed before enrollment in this study. Results: No myocardial infarction was observed during intracoronary infusion. The intracoronary infusion of cells or saline did not result in cardiac enzyme elevation, cardiac perforation or pericardial effusion. No arrhythmia, such as ventricular tachycardia or ventricular fibrillation, was induced by intracoronary infusion. No serious adverse events occurred in either group. The reduction in the frequency of angina episodes per week 3 and 6 months after infusion was significantly higher in the treatment group (-14.6 ± 4.8 at 3 months and -15.6 ± 4.0 at 6 months) than in the control group (-4.5 ± 0.3 and -3.0 ± 1.2, respectively; p < 0.01). Other efficacy parameters such as nitroglycerine usage, exercise time and the Canadian Cardiovascular Society class also showed an improvement in the treatment group compared to the control group. A significant improvement in myocardial perfusion was noted in the treatment group compared to the control group, as measured by single-photon emission computed tomography. Conclusions: This randomized trial investigating intracoronary infusion of autologous CD34+ cells in patients with intractable angina shows the safety and feasibility of this therapy and provides evidence for efficacy. PMID: 20975266 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation and characterization of neural crest stem cells from adult human hair follicles. Folia Biol (Praha). 2010;56(4):149-57 Authors: Krejčí E, Grim M Neural crest (NC) is a transient embryonic tissue, whose cells are motile and multipotent until they reach their destination and differentiate according to microenvironmental cues into a variety of cell types. However, a subpopulation of these cells remains multipotent. They were found, among other locations, in a bulge of adult murine whisker follicle and were designated epidermal neural crest stem cells (EPI-NCSCs). The aim of this work is to ascertain whether the EPI-NCSCs could be isolated from human hair follicles as well. Due to their exceptional properties, they could represent potential candidates for stem cell therapy. The presented work focuses on the isolation and characterization of EPI-NCSCs from human skin. We obtained a population of cells that expressed markers of NC, NC progeny and general stem cell markers. After prolonged cultivation, the subpopulation of cells spontaneously differentiated into some of NC derivatives, i.e. neurons, smooth muscle cells and Schwann cell progenitors. Targeted differentiation with neuregulin 1 highly increased the number of Schwann cells in the culture. Human EPI-NCSCs could also grow under non-adherent conditions and form 3-dimensional spheres. Microarray analysis was performed and gene profile of human EPI-NCSCs was compared with the list of key genes of murine EPI-NCSCs and the list of genes up-regulated in newly induced NC cells. This revealed 94% and 88% similarity, respectively. All presented results strongly support the NCSC identity and multipotency of isolated human cells. These cells could thus be used in regenerative medicine, especially because of the easy accessibility of donor tissue. PMID: 20974047 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Lentiviral vector-mediated knockdown of the neuroglycan 2 proteoglycan or expression of neurotrophin-3 promotes neurite outgrowth in a cell culture model of the glial scar. J Gene Med. 2010 Oct 26; Authors: Donnelly EM, Strappe PM, McGinley LM, Madigan NN, Geurts E, Rooney GE, Windebank AJ, Fraher J, Dockery P, O'Brien T, McMahon SS BACKGROUND: Following spinal cord injury, a highly inhibitory environment for axonal regeneration develops. One of the main sources of this inhibition is the glial scar that is formed after injury by reactive astrocytes. The inhibitory environment is mainly a result of chondroitin sulphate proteoglycans (CSPGs). Neuroglycan 2 (NG2), one of the main inhibitory CSPGs, is up-regulated following spinal cord injury. METHODS: Small interfering RNA (siRNA) was designed to target NG2 and this short hairpin RNA (shRNA) was cloned into a lentiviral vector (LV). The neurotrophic factor neurotrophin-3 (NT-3) promotes the growth and survival of developing neurites and has also been shown to aid regeneration. NT-3 was also cloned into a LV. In vitro assessment of these vectors using a coculture system of dorsal root ganglia (DRG) neurones and Neu7 astrocytes was carried out. The Neu7 cell line is a rat astrocyte cell line that overexpresses NG2, thereby mimicking the inhibitory environment following spinal cord injury. RESULTS AND DISCUSSION: These experiments show that both the knockdown of NG2 via shRNA and over-expression of NT-3 can significantly increase neurite growth, although a combination of both vectors did not confer any additional benefit over the vectors used individually. These LVs show promising potential for growth and survival of neurites in injured central nervous system tissue (CNS). Copyright © 2010 John Wiley & Sons, Ltd. PMID: 20976834 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Primary cellular meningeal defects cause neocortical dysplasia and dyslamination. Ann Neurol. 2010 Oct;68(4):454-64 Authors: Hecht JH, Siegenthaler JA, Patterson KP, Pleasure SJ OBJECTIVE: Cortical malformations are important causes of neurological morbidity, but in many cases their etiology is poorly understood. Mice with Foxc1 mutations have cellular defects in meningeal development. We use hypomorphic and null alleles of Foxc1 to study the effect of meningeal defects on neocortical organization. METHODS: Embryos with loss of Foxc1 activity were generated using the hypomorphic Foxc1(hith) allele and the null Foxc1(lacZ) allele. Immunohistologic analysis was used to assess cerebral basement membrane integrity, marginal zone heterotopia formation, neuronal overmigration, meningeal defects, and changes in basement membrane composition. Dysplasia severity was quantified using 2 measures. RESULTS: Cortical dysplasia resembling cobblestone cortex, with basement membrane breakdown and lamination defects, is seen in Foxc1 mutants. As Foxc1 activity was reduced, abnormalities in basement membrane integrity, heterotopia formation, neuronal overmigration, and meningeal development appeared earlier in gestation and were more severe. Surprisingly, the basement membrane appeared intact at early stages of development in the face of severe deficits in meningeal development. Prominent defects in basement membrane integrity appeared as development proceeded. Molecular analysis of basement membrane laminin subunits demonstrated that loss of the meninges led to changes in basement membrane composition. INTERPRETATION: Cortical dysplasia can be caused by cellular defects in the meninges. The meninges are not required for basement membrane establishment but are needed for remodeling as the brain expands. Specific changes in basement membrane composition may contribute to subsequent breakdown. Our study raises the possibility that primary meningeal defects may cortical dysplasia in some cases. Ann Neurol 2010;68:454-464. PMID: 20976766 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A whole-mechanical method to establish human embryonic stem cell line HN4 from discarded embryos. Cytotechnology. 2010 Oct 26; Authors: Li B, Xu L, Lu WY, Xu W, Wang MH, Yang K, Dong J, Ding XY, Huang YH Since the first human embryonic stem cell (hESC) line was generated by Thomson et al. (in Science 282:1145-1147, 1998), hundreds of hESC lines have been reported by different labs, providing resources for basic research and regenerative medicine as well. However it has been widely recognized that hESC lines varied on their properties, in terms of gene expression profile, epigenetic modify profile, and differentiation tendency. Generation of more hESC lines will largely enhance our knowledge of hESCs innate character. In this current work, we reported the generation of HN4, a hESC line derived from grade III IVF human embryo by using a mixture of human foreskin fibroblast (HFF) and mouse embryonic fibroblast (MEF) as feeder layers, and a whole-mechanical method in inner cell mass (ICM) isolation. HN4 satisfied the criteria of hESCs pluripotency, with high expression of hESC surface markers (SSEA-3, SSEA-4, TRA-1-60, TRA-1-81), transcription factors (OCT-4, NANOG, REX-1), and alkaline phosphatase. It is able to differentiate to three germ layer derivatives when cultured in vitro, or in teratoma formation. Moreover, it displayed promising potential in neural differentiation under a proper culture condition, suggesting the advantage of HN4 in further investigation. Additionally, the whole-mechanical protocol for ICM isolation facilitates hESC line generation for its ease to handle. PMID: 20976554 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow. Cell Mol Life Sci. 2010 Oct 26; Authors: Glejzer A, Laudet E, Leprince P, Hennuy B, Poulet C, Shakhova O, Sommer L, Rogister B, Wislet-Gendebien S Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. PMID: 20976520 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Clones of ectopic stem cells in the regeneration of muscle defects in vivo. PLoS One. 2010;5(10):e13547 Authors: Yang R, Chen M, Lee CH, Yoon R, Lal S, Mao JJ Little is known about whether clones of ectopic, non-muscle stem cells contribute to muscle regeneration. Stem/progenitor cells that are isolated for experimental research or therapeutics are typically heterogeneous. Non-myogenic lineages in a heterogeneous population conceptually may compromise tissue repair. In this study, we discovered that clones of mononucleated stem cells of human tooth pulp fused into multinucleated myotubes that robustly expressed myosin heavy chain in vitro with or without co-culture with mouse skeletal myoblasts (C2C12 cells). Cloned cells were sustainably Oct4+, Nanog+ and Stro1+. The fusion indices of myogenic clones were approximately 16-17 folds greater than their parent, heterogeneous stem cells. Upon infusion into cardio-toxin induced tibialis anterior muscle defects, undifferentiated clonal progenies not only engrafted and colonized host muscle, but also expressed human dystrophin and myosin heavy chain more efficaciously than their parent heterogeneous stem cell populations. Strikingly, clonal progenies yielded ∼9 times more human myosin heavy chain mRNA in regenerating muscles than those infused with their parent, heterogeneous stem cells. The number of human dystrophin positive cells in regenerating muscles infused with clonal progenies was more than ∼3 times greater than muscles infused with heterogeneous stem cells from which clonal progenies were derived. These findings suggest the therapeutic potential of ectopic myogenic clones in muscle regeneration. PMID: 20975999 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | New insights into and novel applications of release technology for periodontal reconstructive therapies. J Control Release. 2010 Oct 22; Authors: Chen FM, An Y, Zhang R, Zhang M Periodontitis, an almost ubiquitous disorder in the adult population, induces the breakdown of tooth-supporting apparatus which, unfortunately, has an extremely limited capacity for self-repair and regeneration. The recent discovery of progenitor/stem cells residing in the periodontium raises the possibility of restoring damaged periodontal tissues by recruiting their latent regenerative potential. However, stem cell fates may be influenced by a number of signaling molecules, such as growth factors (GFs), that require robust control for safe and effective regeneration of functional tissues. Numerous GFs with the ability to promote the regeneration of periodontal tissues have been identified, but their clinical use is often hindered by delivery problems. Regulation of cell activity within a complex in vivo milieu requires the incorporation of multifaceted release technologies that offer physiological levels of GFs, mimicking the natural wound healing cascade by using tools of tissue engineering and protein/gene delivery. This should not be limited to the provision of a single GF but should instead release multiple essential GFs at an optimized ratio in a specific spatiotemporal mode. This article summarizes current limitations and new opportunities related to release technology in periodontal regenerative medicine, highlighting the importance as well as challenges with respect to delivering multiple GFs in an orderly temporal and spatial sequence to mimic their natural expression patterns. Recent progress highlights the importance of releasing endogenous GFs and developing commercially available products that may facilitate clinical translation. PMID: 20974199 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cardiac origin of smooth muscle cells in the inflow tract. J Mol Cell Cardiol. 2010 Oct 22; Authors: Nakano H, Williams E, Hoshijima M, Sasaki M, Minamisawa S, Chien KR, Nakano A Multipotent Isl1(+) heart progenitors give rise to three major cardiovascular cell types; cardiac, smooth muscle, and endothelial cells, and play a pivotal role in lineage diversification during cardiogenesis. A critical question is pinpointing when this cardiac-vascular lineage decision is made, and how this plasticity serves to coordinate cardiac chamber and vessel growth. The posterior domain of the Isl1-positive second heart field contributes to the SLN-positive atrial myocardium and myocardial sleeves in the cardiac inflow tract, where myocardial and vascular smooth muscle layers form anatomical and functional continuity. Herein, using a new atrial specific SLN-Cre knockin mouse line, we report that bipotent Isl1(+)/SLN(+) transient cell population contributes to cardiac as well as smooth muscle cells at the heart-vessel junction in cardiac inflow tract. The Isl1(+)/SLN(+) cells are capable of giving rise to cardiac and smooth muscle cells until late gestational stages. These data suggest that the cardiac and smooth muscle cells in the cardiac inflow tract share a common developmental origin. PMID: 20974149 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Isolation and characterization of neural crest stem cells from adult human hair follicles. Folia Biol (Praha). 2010;56(4):149-57 Authors: Krejčí E, Grim M Neural crest (NC) is a transient embryonic tissue, whose cells are motile and multipotent until they reach their destination and differentiate according to microenvironmental cues into a variety of cell types. However, a subpopulation of these cells remains multipotent. They were found, among other locations, in a bulge of adult murine whisker follicle and were designated epidermal neural crest stem cells (EPI-NCSCs). The aim of this work is to ascertain whether the EPI-NCSCs could be isolated from human hair follicles as well. Due to their exceptional properties, they could represent potential candidates for stem cell therapy. The presented work focuses on the isolation and characterization of EPI-NCSCs from human skin. We obtained a population of cells that expressed markers of NC, NC progeny and general stem cell markers. After prolonged cultivation, the subpopulation of cells spontaneously differentiated into some of NC derivatives, i.e. neurons, smooth muscle cells and Schwann cell progenitors. Targeted differentiation with neuregulin 1 highly increased the number of Schwann cells in the culture. Human EPI-NCSCs could also grow under non-adherent conditions and form 3-dimensional spheres. Microarray analysis was performed and gene profile of human EPI-NCSCs was compared with the list of key genes of murine EPI-NCSCs and the list of genes up-regulated in newly induced NC cells. This revealed 94% and 88% similarity, respectively. All presented results strongly support the NCSC identity and multipotency of isolated human cells. These cells could thus be used in regenerative medicine, especially because of the easy accessibility of donor tissue. PMID: 20974047 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Differential gene expression pattern of diabetic rat retinas after intravitreal injection of erythropoietin. Clin Experiment Ophthalmol. 2010 Oct 25; Authors: Chu Q, Zhang J, Wu Y, Zhang Y, Xu G, Li W, Xu GT Background: To profile the pattern of gene expression in diabetic rat retinas with or without intravitreal injection of erythropoietin. Design: By using streptozotocin-induced diabetic rats, after intravitreal injection of erythropoietin, neurosensory retinas were collected to determine the effect of erythropoietin on gene expression. Participants: Three groups of Sprague-Dawley rats were studied: normal control (15), diabetic rats with saline injection (15) and diabetes with intravitreal erythropoietin treatment (15). Methods: Diabetes was induced by intra-peritoneal injection of streptozotocin. Intravitreal injection of erythropoietin was performed at the following time points: 0, 30 and 120 days after diabetes onset. Four days after each injection at above time points, the retinas were harvested for microarray assay. The real-time PCR was used to evaluate the microarray data. Results: Genes encoding inflammatory factors, such as IL-2 and IL-11, which were up-regulated in the diabetic retinas, were restored after erythropoietin treatment. Genes encoding pro-apoptotic effectors, like Tnfrsf5, Bid3 and Bcl2l1, were also up-regulated in diabetic rats and attenuated in erythropoietin-treated group. In addition, real-time PCR were employed to confirm the changes of the genes Trex2, G1P2, DHX58, RGD1311906 and LOC689064, which have not been reported in diabetic retinopathy. Conclusions: Intravitreal erythropoietin treatment is able to normalize the gene expression responsible for pro-apoptotic and inflammatory responses noted in diabetic retinas. PMID: 20973890 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Experimental treatments for hypoxic ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):369-77 Authors: Kelen D, Robertson NJ Hypoxic ischaemic encephalopathy continues to be a significant cause of death and disability worldwide. In the last 1-2 years, therapeutic hypothermia has entered clinical practice in industrialized countries and neuroprotection of the newborn has become a reality. The benefits and safety of cooling under intensive care settings have been shown consistently in trials; therapeutic hypothermia reduces death and neurological impairment at 18 months with a number needed to treat of approximately nine. Unfortunately, around half the infants who receive therapeutic hypothermia still have abnormal outcomes. Recent experimental data suggest that the addition of another agent to cooling may enhance overall protection either additively or synergistically. This review discusses agents such as inhaled xenon, N-acetylcysteine, melatonin, erythropoietin and anticonvulsants. The role of biomarkers to speed up clinical translation is discussed, in particular, the use of the cerebral magnetic resonance spectroscopy lactate/N-acetyl aspartate peak area ratios to provide early prognostic information. Finally, potential future therapies such as regeneration/repair and postconditioning are discussed. PMID: 20570449 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Fat grafting to the breast and adipose-derived stem cells: recent scientific consensus and controversy. Aesthet Surg J. 2010 May;30(3):381-7 Authors: Mizuno H, Hyakusoku H Recent technical advances in fat grafting and the development of surgical devices such as liposuction cannulae have made fat grafting a relatively safe and effective procedure. However, new guidelines issued by the American Society of Plastic Surgeons in 2009 announced that fat grafting to the breast is not a strongly recommended procedure, as there are limited scientific data on the safety and efficacy of this particular type of fat transfer. Recent progress by several groups has revealed that multipotent adult stem cells are present in human adipose tissue. This cell population, termed adipose-derived stem cells (ADSC), represents a promising approach to future cell-based therapies, such as tissue engineering and regeneration. In fact, several reports have shown that ADSC play a pivotal role in graft survival through both adipogenesis and angiogenesis. Although tissue augmentation by fat grafting does have several advantages in that it is a noninvasive procedure and results in minimal scarring, it is essential that such a procedure be supported by evidence-based medicine and that further basic scientific and clinical research is conducted to ensure that fat grafting is a safe and effective procedure. PMID: 20601560 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Clones of ectopic stem cells in the regeneration of muscle defects in vivo. PLoS One. 2010;5(10):e13547 Authors: Yang R, Chen M, Lee CH, Yoon R, Lal S, Mao JJ Little is known about whether clones of ectopic, non-muscle stem cells contribute to muscle regeneration. Stem/progenitor cells that are isolated for experimental research or therapeutics are typically heterogeneous. Non-myogenic lineages in a heterogeneous population conceptually may compromise tissue repair. In this study, we discovered that clones of mononucleated stem cells of human tooth pulp fused into multinucleated myotubes that robustly expressed myosin heavy chain in vitro with or without co-culture with mouse skeletal myoblasts (C2C12 cells). Cloned cells were sustainably Oct4+, Nanog+ and Stro1+. The fusion indices of myogenic clones were approximately 16-17 folds greater than their parent, heterogeneous stem cells. Upon infusion into cardio-toxin induced tibialis anterior muscle defects, undifferentiated clonal progenies not only engrafted and colonized host muscle, but also expressed human dystrophin and myosin heavy chain more efficaciously than their parent heterogeneous stem cell populations. Strikingly, clonal progenies yielded ∼9 times more human myosin heavy chain mRNA in regenerating muscles than those infused with their parent, heterogeneous stem cells. The number of human dystrophin positive cells in regenerating muscles infused with clonal progenies was more than ∼3 times greater than muscles infused with heterogeneous stem cells from which clonal progenies were derived. These findings suggest the therapeutic potential of ectopic myogenic clones in muscle regeneration. PMID: 20975999 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | New insights into and novel applications of release technology for periodontal reconstructive therapies. J Control Release. 2010 Oct 22; Authors: Chen FM, An Y, Zhang R, Zhang M Periodontitis, an almost ubiquitous disorder in the adult population, induces the breakdown of tooth-supporting apparatus which, unfortunately, has an extremely limited capacity for self-repair and regeneration. The recent discovery of progenitor/stem cells residing in the periodontium raises the possibility of restoring damaged periodontal tissues by recruiting their latent regenerative potential. However, stem cell fates may be influenced by a number of signaling molecules, such as growth factors (GFs), that require robust control for safe and effective regeneration of functional tissues. Numerous GFs with the ability to promote the regeneration of periodontal tissues have been identified, but their clinical use is often hindered by delivery problems. Regulation of cell activity within a complex in vivo milieu requires the incorporation of multifaceted release technologies that offer physiological levels of GFs, mimicking the natural wound healing cascade by using tools of tissue engineering and protein/gene delivery. This should not be limited to the provision of a single GF but should instead release multiple essential GFs at an optimized ratio in a specific spatiotemporal mode. This article summarizes current limitations and new opportunities related to release technology in periodontal regenerative medicine, highlighting the importance as well as challenges with respect to delivering multiple GFs in an orderly temporal and spatial sequence to mimic their natural expression patterns. Recent progress highlights the importance of releasing endogenous GFs and developing commercially available products that may facilitate clinical translation. PMID: 20974199 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Microscale versus Nanoscale Scaffold Architecture for Mesenchymal Stem Cell Chondrogenesis. Tissue Eng Part A. 2010 Oct 26; Authors: Shanmugasundaram S, Arinzeh T Nanofiber scaffolds, produced by the electrospinning technique, have gained widespread attention in tissue engineering due to their morphological similarities to the native extracellular matrix. For cartilage repair, studies have examined their feasibility; however these studies have been limited, excluding the influence of other scaffold design features. This study evaluated the effect of scaffold design, specifically examining a range of nano to micron-sized fibers and resulting pore size and mechanical properties, on human mesenchymal stem cells (MSCs) derived from the adult bone marrow during chondrogenesis. MSC differentiation was examined on these scaffolds with an emphasis on temporal gene expression of chondrogenic markers and the pluripotent gene, Sox2, which has yet to be explored for MSCs during chondrogenesis and in combination with tissue engineering scaffolds. Chondrogenic markers of aggrecan, chondroadherin, sox9, and collagen type II were highest for cells on micron-sized fibers (5 and 9 m) with pore sizes of 27 and 29 m, respectively, in comparison to cells on nanosized fibers (300 nm and 600 to 1400 nm) having pore sizes of 2 and 3 m, respectively. Undifferentiated MSCs expressed high levels of the Sox2 gene but displayed negligible levels on all scaffolds with or without the presence of inductive factors suggesting the physical features of the scaffold play an important role in differentiation. Micron-sized fibers with large pore structures and mechanical properties comparable to the cartilage ECM enhanced chondrogenesis, demonstrating architectural features as well as mechanical properties of electrospun fibrous scaffolds enhance differentiation. PMID: 20973751 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
No comments:
Post a Comment