| Mesenchymal stem cells for bone repair and metabolic bone diseases.
October 3, 2009 at 8:52 am
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| | Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin Proc. 2009 Oct;84(10):893-902 Authors: Undale AH, Westendorf JJ, Yaszemski MJ, Khosla S Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases. PMID: 19797778 [PubMed - in process] |
| Cardiac cell repair therapy: a clinical perspective.
October 3, 2009 at 8:52 am
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| | Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc. 2009 Oct;84(10):876-92 Authors: Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A From bone marrow transplants 5 decades ago to the most recent stem cell-derived organ transplants, regenerative medicine is increasingly recognized as an emerging core component of modern practice. In cardiovascular medicine, innovation in stem cell biology has created curative solutions for the treatment of both ischemic and nonischemic cardiomyopathy. Multiple cell-based platforms have been developed, harnessing the regenerative potential of various natural and bioengineered sources. Clinical experience from the first 1000 patients (approximately) who have received stem cell therapy worldwide indicates a favorable safety profile with modest improvement in cardiac function and structural remodeling in the setting of acute myocardial infarction or chronic heart failure. Further investigation is required before early adoption and is ongoing. Broader application in practice will require continuous scientific advances to match each patient with the most effective reparative phenotype, while ensuring optimal cell delivery, dosing, and timing of intervention. An interdisciplinary effort across the scientific and clinical community within academia, biotechnology, and government will drive the successful realization of this next generation of therapeutic agents for the "broken" heart. PMID: 19797777 [PubMed - in process] |
| Stem cell therapy and regenerative medicine.
October 3, 2009 at 8:52 am
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| | Stem cell therapy and regenerative medicine. Mayo Clin Proc. 2009 Oct;84(10):859-61 Authors: O'Brien T, Barry FP PMID: 19797773 [PubMed - in process] |
| Oxysterols drive dopaminergic neurogenesis from stem cells.
October 3, 2009 at 8:52 am
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| | Oxysterols drive dopaminergic neurogenesis from stem cells. Cell Stem Cell. 2009 Oct 2;5(4):343-4 Authors: Ma DK, Ming GL, Song H Stem cell therapy for Parkinson's disease requires effective production of dopaminergic neurons. In this issue of Cell Stem Cell, Sacchetti et al. (2009) report an unexpected role of liver X receptors and their ligand, oxysterols, in regulating dopaminergic neurogenesis. PMID: 19796609 [PubMed - in process] |
| Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates.
October 3, 2009 at 7:38 am
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| | Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann Neurol. 2009 May 11;66(3):343-354 Authors: Pluchino S, Gritti A, Blezer E, Amadio S, Brambilla E, Borsellino G, Cossetti C, Del Carro U, Comi G, 't Hart B, Vescovi A, Martino G OBJECTIVE: Transplanted neural stem/precursor cells (NPCs) display peculiar therapeutic plasticity in vivo. Although the replacement of cells was first expected as the prime therapeutic mechanism of stem cells in regenerative medicine, it is now clear that transplanted NPCs simultaneously instruct several therapeutic mechanisms, among which replacement of cells might not necessarily prevail. A comprehensive understanding of the mechanism(s) by which NPCs exert their therapeutic plasticity is lacking. This study was designed as a preclinical approach to test the feasibility of human NPC transplantation in an outbreed nonhuman primate experimental autoimmune encephalomyelitis (EAE) model approximating the clinical and complex neuropathological situation of human multiple sclerosis (MS) more closely than EAE in the standard laboratory rodent. METHODS: We examined the safety and efficacy of the intravenous (IV) and intrathecal (IT) administration of human NPCs in common marmosets affected by human myelin oligodendrocyte glycoprotein 1-125-induced EAE. Treatment commenced upon the occurrence of detectable brain lesions on a 4.7T spectrometer. RESULTS: EAE marmosets injected IV or IT with NPCs accumulated lower disability and displayed increased survival, as compared with sham-treated controls. Transplanted NPCs persisted within the host central nervous system (CNS), but were also found in draining lymph nodes, for up to 3 months after transplantation and exhibited remarkable immune regulatory capacity in vitro. INTERPRETATION: Herein, we provide the first evidence that human CNS stem cells ameliorate EAE in nonhuman primates without overt side effects. Immune regulation (rather than neural differentiation) is suggested as the major putative mechanism by which NPCs ameliorate EAE in vivo. Our findings represent a critical step toward the clinical use of human NPCs in MS. Ann Neurol 2009;66:343-354. PMID: 19798728 [PubMed - as supplied by publisher] |
| In vivo dynamics of human cord blood-derived CD34(-) SCID-repopulating cells using intra-bone marrow injection.
October 3, 2009 at 7:38 am
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| | In vivo dynamics of human cord blood-derived CD34(-) SCID-repopulating cells using intra-bone marrow injection. Leukemia. 2009 Oct 1; Authors: Kimura T, Matsuoka Y, Murakami M, Kimura T, Takahashi M, Nakamoto T, Yasuda K, Matsui K, Kobayashi K, Imai S, Asano H, Nakatsuka R, Uemura Y, Sasaki Y, Sonoda Y The identification of human CD34-negative (CD34(-)) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. This study investigated the long-term repopulating capacity and redistribution kinetics of human cord blood-derived CD34(-) severe combined immunodeficiency (SCID)-repopulating cells (SRCs) and compared them with those of CD34(+)CD38(+) and CD34(+)CD38(-) SRCs using the intra-bone marrow injection (IBMI) to clarify the characteristics of CD34(-) SRCs. On the basis of the limiting dilution analyses data, estimated numbers of CD34(+)CD38(+), CD34(+)CD38(-), and CD34(-) SRCs were transplanted to NOD/SCID mice by IBMI. The human cell repopulation at the site of injection and the other bones were serially investigated. Interestingly, CD34(+)CD38(+), CD34(+)CD38(-), and CD34(-) SRCs began to migrate to other bones 2 and 5 weeks after the transplantation, respectively. Accordingly, the initiation of migration seemed to differ between the CD34(+) and CD34(-) SRCs. In addition, CD34(+)CD38(+) SRCs only sustained a short-term repopulation. However, both CD34(+)CD38(-) and CD34(-) SRCs had longer-term repopulation capacity. Taken together, these findings showed that CD34(-) SRCs show different in vivo kinetics, thus suggesting that the identified CD34(-) SRCs are a distinct class of primitive HSCs in comparison to the CD34(+)CD38(+) and CD34(+)CD38(-) SRCs.Leukemia advance online publication, 1 October 2009; doi:10.1038/leu.2009.206. PMID: 19798093 [PubMed - as supplied by publisher] |
| Mesenchymal stem cells for bone repair and metabolic bone diseases.
October 3, 2009 at 7:38 am
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| | Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin Proc. 2009 Oct;84(10):893-902 Authors: Undale AH, Westendorf JJ, Yaszemski MJ, Khosla S Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases. PMID: 19797778 [PubMed - in process] |
| Cardiac cell repair therapy: a clinical perspective.
October 3, 2009 at 7:38 am
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| | Cardiac cell repair therapy: a clinical perspective. Mayo Clin Proc. 2009 Oct;84(10):876-92 Authors: Gersh BJ, Simari RD, Behfar A, Terzic CM, Terzic A From bone marrow transplants 5 decades ago to the most recent stem cell-derived organ transplants, regenerative medicine is increasingly recognized as an emerging core component of modern practice. In cardiovascular medicine, innovation in stem cell biology has created curative solutions for the treatment of both ischemic and nonischemic cardiomyopathy. Multiple cell-based platforms have been developed, harnessing the regenerative potential of various natural and bioengineered sources. Clinical experience from the first 1000 patients (approximately) who have received stem cell therapy worldwide indicates a favorable safety profile with modest improvement in cardiac function and structural remodeling in the setting of acute myocardial infarction or chronic heart failure. Further investigation is required before early adoption and is ongoing. Broader application in practice will require continuous scientific advances to match each patient with the most effective reparative phenotype, while ensuring optimal cell delivery, dosing, and timing of intervention. An interdisciplinary effort across the scientific and clinical community within academia, biotechnology, and government will drive the successful realization of this next generation of therapeutic agents for the "broken" heart. PMID: 19797777 [PubMed - in process] |
| Stem cell therapy and regenerative medicine.
October 3, 2009 at 7:38 am
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| | Stem cell therapy and regenerative medicine. Mayo Clin Proc. 2009 Oct;84(10):859-61 Authors: O'Brien T, Barry FP PMID: 19797773 [PubMed - in process] |
| Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells.
October 3, 2009 at 7:38 am
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| | Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells. Cell Stem Cell. 2009 Oct 2;5(4):409-19 Authors: Sacchetti P, Sousa KM, Hall AC, Liste I, Steffensen KR, Theofilopoulos S, Parish CL, Hazenberg C, Richter LA, Hovatta O, Gustafsson JA, Arenas E Control over progenitor proliferation and neurogenesis remains a key challenge for stem cell neurobiology and a prerequisite for successful stem cell replacement therapies for neurodegenerative diseases like Parkinson's disease (PD). Here, we examined the function of two nuclear receptors, liver X receptors (Lxralpha and beta) and their ligands, oxysterols, as regulators of cell division, ventral midbrain (VM) neurogenesis, and dopaminergic (DA) neuron development. Deletion of Lxrs reduced cell cycle progression and VM neurogenesis, resulting in decreased DA neurons at birth. Activation of Lxrs with oxysterol ligands increased the number of DA neurons in mouse embryonic stem cells (ESCs) and in wild-type but not Lxralphabeta(-/-) VM progenitor cultures. Likewise, oxysterol treatment of human ESCs (hESCs) during DA differentiation increased neurogenesis and the number of mature DA neurons, while reducing proliferating progenitors. Thus, Lxr ligands may improve current hESC replacement strategies for PD by selectively augmenting the generation of DA neurons. PMID: 19796621 [PubMed - in process] |
| ISSCR 2009 Industry Panel Session: promoting translation and commercialization.
October 3, 2009 at 7:38 am
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| | ISSCR 2009 Industry Panel Session: promoting translation and commercialization. Cell Stem Cell. 2009 Oct 2;5(4):379-84 Authors: Mason C This report presents the recommendations to the ISSCR leadership from the industry panel session at the 2009 annual conference. The seven recommendations address core issues essential for the promotion of stem cell and regenerative medicine translation and commercialization. PMID: 19796618 [PubMed - in process] |
| Regeneration next: toward heart stem cell therapeutics.
October 3, 2009 at 7:38 am
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| | Regeneration next: toward heart stem cell therapeutics. Cell Stem Cell. 2009 Oct 2;5(4):364-77 Authors: Hansson EM, Lindsay ME, Chien KR Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and their patients. However, the translational arm of stem cell science is in a relatively primitive state. Although a number of clinical studies have been initiated, the early returns point to several inherent problems. In this regard, the clinical potential of stem cells can only be fully realized by the identification of the key barriers to clinical implementation. Here, we examine experimental paradigms to address the critical steps in the transition from stem cell biology to regenerative medicine, utilizing cardiovascular disease as a case study. PMID: 19796617 [PubMed - in process] |
| Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2.
October 3, 2009 at 7:38 am
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| | Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell. 2009 Oct 2;5(4):353-7 Authors: Giorgetti A, Montserrat N, Aasen T, Gonzalez F, Rodríguez-Pizà I, Vassena R, Raya A, Boué S, Barrero MJ, Corbella BA, Torrabadella M, Veiga A, Izpisua Belmonte JC PMID: 19796614 [PubMed - in process] |
| PARylation: strengthening the connection between cancer and pluripotency.
October 3, 2009 at 7:38 am
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| | PARylation: strengthening the connection between cancer and pluripotency. Cell Stem Cell. 2009 Oct 2;5(4):349-50 Authors: Deng W Pluripotency and tumorgenicity appear fundamentally linked. Recent investigations into the role of PARylation in chromatin remodeling (Ahel et al., 2009; Gottschalk et al., 2009), combined with the demonstration that p53 serves as a barrier to pluripotency (Banito et al., 2009), further strengthen this connection. PMID: 19796612 [PubMed - in process] |
| Ten years of cord blood transplantation: from bench to bedside.
October 3, 2009 at 7:38 am
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| | Ten years of cord blood transplantation: from bench to bedside. Br J Haematol. 2009 Oct;147(2):192-9 Authors: Gluckman E Cord blood is an unlimited source of haematopoietic stem cells for allogeneic haematopoietic stem cell transplant. Since the first human cord blood transplant, cord blood banks have been established worldwide for collection and cryopreservation of cord blood for allogeneic haematopoietic stem cell transplant. More than 400 000 cord blood units are now available for international exchange. Results of unrelated allogeneic cord blood transplants in malignant and non-malignant diseases, in adults and children, show that, compared to human leucocyte antigen (HLA)-matched unrelated bone marrow transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of graft-versus-host disease and better long-term immune recovery resulting in a similar long term survival. Several studies have shown that the number of cells is the most important factor for engraftment while some degree of HLA mismatches is acceptable. Progress is expected to facilitate engraftment and reduce transplant-related mortality and includes reduced intensity conditioning regimen, intra bone injection of cord blood cells and double cord blood transplants. In addition to haematopoietic stem cells, cord blood and placenta contain a high number of non-haematopoietic stem cells that explains the increasing interest of using cord blood for developing regenerative medicine. PMID: 19796268 [PubMed - in process] |
| Non-haematological uses of cord blood stem cells.
October 3, 2009 at 7:38 am
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| | Non-haematological uses of cord blood stem cells. Br J Haematol. 2009 Oct;147(2):177-84 Authors: Harris DT Embryonic stem (ES) cell therapies are often promoted as the optimal stem cell source for regenerative medicine applications because of their ability to develop into any tissue in the body. Unfortunately, ES cell applications are currently limited by ethical, political, biological and regulatory hurdles. However, multipotent non-ES cells are available in large numbers in umbilical cord blood (CB). CB stem cells are capable of giving rise to hematopoietic, epithelial, endothelial and neural tissues both in vitro and in vivo. Thus, CB stem cells are amenable to treat a wide variety of diseases including cardiovascular, ophthalmic, orthopaedic, neurological and endocrine diseases. In addition, the recent use of CB in several regenerative medicine clinical studies has demonstrated its pluripotent nature. Here we review the latest developments in the use of CB in regenerative medicine. Examples of these usages include cerebral palsy and type I diabetes. The numbers of individuals affected with each of these diseases are estimated at 10 000 infants diagnosed with cerebral palsy annually and 15 000 youths diagnosed with type 1 diabetes annually. A summary of the initial results from such clinical studies using autologous cord blood stem cells will be presented. PMID: 19796266 [PubMed - in process] |
| Tumors originating from induced pluripotent stem cells and methods for their prevention.
October 3, 2009 at 7:38 am
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| | Tumors originating from induced pluripotent stem cells and methods for their prevention. Ann N Y Acad Sci. 2009 Sep;1176:197-204 Authors: Duinsbergen D, Salvatori D, Eriksson M, Mikkers H Pluripotent stem cells represent an almost unlimited source of most somatic cell types, providing them with great potential for cell-based therapies. The earliest methods used for generating human pluripotent stem cells as embryonic stem cells from human embryos suffered from ethical and technical drawbacks. These problems have been solved in part through the efficient induction of pluripotency in somatic cells using forced expression of a tetrad of factors. Here, we describe the formation of rhabdomyosarcomas originating from factor-induced pluripotent stem (iPS) cells derived from mouse neural stem cells. This underscores the commonly accepted notion that the use of retroviral delivery methods for inducing pluripotency will not be suited for clinical applications. However, the iPS cell field is developing rapidly. Safer protocols are now available for producing pluripotent stem cells. Here the current state-of-the-art in this field will be discussed. PMID: 19796248 [PubMed - in process] |
| Phenotypic characterization of distinct human bone marrow-derived MSC subsets.
October 3, 2009 at 7:38 am
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| | Phenotypic characterization of distinct human bone marrow-derived MSC subsets. Ann N Y Acad Sci. 2009 Sep;1176:124-34 Authors: Bühring HJ, Treml S, Cerabona F, de Zwart P, Kanz L, Sobiesiak M Very recently, we identified two distinct mesenchymal stem cell (MSC) subsets in primary bone marrow (BM) that differ in their expression pattern (CD271(bright)MSCA-1(dim)CD56(+) and CD271(bright)MSCA-1(bright)CD56(-)) and morphology as well as in their clonogenic and differentiation capacity. Here we analyzed the cell surface antigen expression in these subsets in more detail and compared the profiles with the expression pattern on cultured MSCs. Most of the tested antigens, including CD13, CD15, CD73, CD140b, CD144, CD146, and CD164, are expressed at similar levels in both primary BM populations. However, a number of markers were differentially expressed. Of these, CD166 (ALCAM), CD200, and CD106 (VCAM-1) showed an almost selective expression on either CD271(bright)MSCA-1(dim)CD56(+) (increased CD166 and CD200 expression) or CD271(bright)MSCA-1(bright)CD56(-) (increased CD106 expression) MSCs, respectively. Additional markers with elevated expression on CD56(+) MSCs include F9-3C2F1, HEK-3D3, HEK5-1B3, and W1C3 antigens, whereas CD10, CD26, CD106, 7C5G1, 9A3G2, 56A1C2, 66E2D11, HEK-3D6, HEK4-1A1, HEK4-2D6, W1D6, W4A5, W7C6, and W8B2 (MSCA-1) antigens showed increased expression in the CD56(-) population. The majority of the analyzed markers found on primary MSCs were also expressed on cultured MSCs. However, in contrast to primary MSCs, HEK7-1C4, W1C3, W1D6, and W4A5 antigens were absent on the cultured counterparts. 7G5G1 and 9A3G2 antigens showed reduced, and HEK-3D6, F9-3C2, and HEK-3D3 showed increased expression on cultured cells. The extended knowledge about the phenotype of the two subsets and the identification of novel MSC markers may result in the isolation of attractive starting populations for applications in regenerative medicine. PMID: 19796240 [PubMed - in process] |
| iPS cells reprogrammed from mesenchymal-like stem/progenitor cells of dental tissue origin.
October 3, 2009 at 7:38 am
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| | iPS cells reprogrammed from mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev. 2009 Oct 1; Authors: Yan X, Qin H, Qu C, Tuan RS, Shi S, Huang GT Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. Many types of cells have been successfully reprogrammed into iPS cells in the mouse system, however, reprogramming human cells have been more difficult. To date, human dermal fibroblasts are the most accessible and feasible cell source for iPS generation. Dental tissues derived from ectomesenchyme harbor mesenchymal-like stem/progenitor cells and some of the tissues have been treated as biomedical wastes, e.g., exfoliated primary teeth and extracted third molars. We asked whether stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells. The four factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2 carried by viral vectors were used to reprogram three different dental stem/progenitor cells: stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP) and dental pulp stem cells (DPSCs). We showed that all three can be reprogrammed into iPS cells and appeared to be at a higher rate than fibroblasts. They exhibited a morphology indistinguishable from human embryonic stem (hES) cells in cultures and expressed hES cell markers SSEA-4, TRA-1-60, TRA-1-80, TRA-2-49, Nanog, Oct4 and Sox2. They formed embryoid bodies in vitro and teratomas in vivo containing tissues of all three germ layers. We conclude that cells of ectomesenchymal origin serve as an excellent alternative source for generating iPS cells. PMID: 19795982 [PubMed - as supplied by publisher] |
| A keratin biomaterial gel hemostat derived from human hair: evaluation in a rabbit model of lethal liver injury.
October 3, 2009 at 7:38 am
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| | A keratin biomaterial gel hemostat derived from human hair: evaluation in a rabbit model of lethal liver injury. J Biomed Mater Res B Appl Biomater. 2009 Jul;90(1):45-54 Authors: Aboushwareb T, Eberli D, Ward C, Broda C, Holcomb J, Atala A, Van Dyke M Effective hemostatic dressings that are compatible with tissues are needed. Keratins are a class of biomaterials that can be derived by extraction of proteins from human hair. We have recently discovered that keratin biomaterials have hemostatic characteristics and hypothesize that a keratin hydrogel having the ability to absorb fluid and bind cells may be an effective hemostat. The goal of this study was to test a keratin hydrogel and evaluate it compared to current hemostats. Thirty-two New Zealand white rabbits received a lethal liver injury. Eight animals each were assigned to negative control, QuickClot, HemCon bandage, and keratin treatment groups. Vital stats and other data were recorded during surgery and all surviving animals were sacrificed after 72 h. Histology was conducted on all surviving animals. Twenty-four-hour survival rates were 0%, 62.5%, 62.5%, and 75% for the negative control, QuickClot, HemCon, and keratin groups, respectively. Other outcomes included blood loss, mean arterial pressure, heart rate, shock index, and liver histology. All of the hemostats were statistically better than the negative control group at late operative time points. The keratin group consistently performed as well as, or better than, the commercial hemostats. Histology showed an interesting healing response at the hemostat-liver interface in the keratin group. PMID: 18988274 [PubMed - indexed for MEDLINE] | | | 
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