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Enactment of a Law for Governmental Support of the Use of Cord Blood, and Ethical Issues.

International Journal of Stem Cells.2012;5(1):84-87.

In Korea, cord blood banking projects have been developed since 1996, and the 1st successful cord blood transplant was performed in 1998. Recently, "Cord Blood Management and Research Act" was legislated in 2010, and has been come into effect on July 1st, 2011. This review focuses the backgrounds, aims, and legislation process as well as principal articles in this act.
Fetal Blood ; Jurisprudence ; Korea ; Transplants

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In vivo Tracking of Human Neural Stem Cells Following Transplantation into a Rodent Model of Ischemic Stroke.

Da Jeong CHANG ; Hyeyoung MOON ; Yong Hyun LEE ; Nayeon LEE ; Hong J LEE ; Iksoo JEON ; Hyunseung LEE ; Tae Sun HWANG ; Seung Hun OH ; Dong Ah SHIN ; Seung U KIM ; Kwan Soo HONG ; Jihwan SONG

International Journal of Stem Cells.2012;5(1):79-83.

BACKGROUND AND OBJECTIVES: Ischemic stroke caused by middle cerebral artery occlusion (MCAo) is the major type of stroke, but there are currently very limited options for cure. It has been shown that neural stem cells (NSCs) or neural precursor cells (NPCs) can survive and improve neurological deficits when they are engrafted in animal models of various neurological diseases. However, how the transplanted NSCs or NPCs are act in vivo in the injured or diseased brain is largely unknown. In this study, we utilized magnetic resonance imaging (MRI) techniques in order to understand the fates of human NSCs (HB1.F3) following transplantation into a rodent model of MCAo. METHODS AND RESULTS: HB1.F3 human NSCs were pre-labeled with ferumoxides (Feridex(R))-protamine sulfate complexes, which were visualized and examined by MRI up to 9 weeks after transplantation. Migration of the transplanted cells to the infarct area was further confirmed by histological methods. CONCLUSIONS: Based on these observations, we speculate that the transplanted NSCs have the extensive migratory ability to the injured site, which will in turn contribute to functional recovery in stroke.
Brain ; Dextrans ; Humans ; Infarction, Middle Cerebral Artery ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Models, Animal ; Neural Stem Cells ; Rodentia ; Stroke ; Track and Field ; Transplants

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Clinical Response of 277 Patients with Spinal Cord Injury to Stem Cell Therapy in Iraq.

Abdulmajeed Alwan HAMMADI ; Andolina MARINO ; Saad FARHAN

International Journal of Stem Cells.2012;5(1):76-78.

BACKGROUND AND OBJECTIVES: Spinal cord injury is a common neurological problem secondary to car accidents, war injuries and other causes, it may lead to varying degrees of neurological disablement, and apart from physiotherapy there is no available treatment to regain neurological function loss. Our aim is to find a new method using autologous hematopoietic stem cells to gain some of the neurologic functions lost after spinal cord injury. METHODS AND RESULTS: 277 patients suffering from spinal cord injury were submitted to an intrathecally treatment with peripheral stem cells. The cells were harvested from the peripheral blood after a treatment with G-CSF and then concentrated to 4~6 ml. 43% of the patients improved; ASIA score shifted from A to B in 88 and from A to C in 32. The best results were achieved in patients treated within one year from the injury. CONCLUSIONS: Since mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than mesenchymal cell cultivation prior to injection. It seems reasonable treatment for spinal cord injury.
Asia ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cells ; Humans ; Iraq ; Spinal Cord ; Spinal Cord Injuries ; Stem Cells ; Stress, Psychological

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Treatment of Spinal Muscolar Atrophy with Intrathecal Mesenchymal Cells.

Marino ANDOLINA

International Journal of Stem Cells.2012;5(1):73-75.

BACKGROUND AND OBJECTIVES: SMA1 is a genetic disease that leads to a progressive apoptosis of the second motoneuron and then to a complete paralysis. There are reports of efficacy of mesenchymal cells in the treatment of other neurological diseases; therefore we decided to treat some children with these cells. METHODS AND RESULTS: Four children suffering from SMA1 were treated by means of intrathecal injections of mesenchymal cells. All patients improved their motility after three weeks. The effect was relevant at the distal muscles, while the proximal ones were less affected. The treatment was repeated once a month for 3~8 months as the effect of the treatment lasted not more than 30 days. One patient who withdrew the treatment died after 45 days. Another patient resulted completely paralysed after two months after quitting the cell therapy but he regained the skills after a new injection. Two patients are stable after the first improvement. CONCLUSIONS: Intrathecal injections of mesenchymal cells improve the motility of children suffering from SMA1. We argue that an early treatment, before the onset of irreversible neurological damages, could result in the cure of this disease.
Apoptosis ; Atrophy ; Child ; Humans ; Injections, Spinal ; Muscles ; Paralysis ; Stem Cells ; Stress, Psychological ; Tissue Therapy

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The Role of PEC Progenitors in ADPKD Progression.

Daniele LODI ; Giulia LIGABUE ; Valentina LUPO ; Fabrizio CAVAZZINI

International Journal of Stem Cells.2012;5(1):65-72.

BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease is a pathology mainly characterized by the progressive development and enlargement of cysts in each kidneys. Such as many adult epithelial tissue, renal tubule replaces damaged or death cells through the presence of stem/progenitor cells CD133+CD24+ Obviously, in ADPKD the repair of damages is insufficient to block the disease, but renal stem cells could have a role in the pathology. In this study we investigate the localization and the involvement of cells CD133+CD24+ in ADPKD progression. METHODS AND RESULTS: Two normal kidneys and two ADPKD kidneys were examined. CD133 and CD24 expression was investigated by confocal microscopy and immunoblotting. Renal tissue and cells were analyzed. CD133 and CD24 have the same localization in ADPKD tissues and in normal kidneys: a subset of epithelial cells (PEC) of Bowman's capsule and luminal side of tubules. It is interesting that CD133+CD24+ cells are statistically more represented in ADPKD tubules (p<0.001) and in healthy glomeruli (p=0.0016). Cysts express CD133 and CD24. CONCLUSIONS: Renal epithelial progenitors demonstrate to be involved in ADPKD pathogenesis but their role will have to be clarified and possibly managed to obtain improvement, or at least stabilization, of disease.
Adult ; Bowman Capsule ; Epithelial Cells ; Humans ; Immunoblotting ; Kidney ; Microscopy, Confocal ; Phenobarbital ; Polycystic Kidney, Autosomal Dominant ; Stem Cells

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Effect of Stem Cell Therapy on Induced Diabetic Keratopathy in Albino Rat.

Maha Baligh ZICKRI ; Nagwa Abdel Wahab AHMAD ; Zeinab Mohamad EL MAADAWI ; Yasmin Kamal MOHAMADY ; Hala Gabr METWALLY

International Journal of Stem Cells.2012;5(1):57-64.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (DM) is a prevalent disorder. Diabetic keratopathy is a well-known ocular complication secondary to type 2 DM. Topical insulin application did not affect apoptosis and necrosis levels in corneal epithelium. Autologous cell transplantation is not a viable option for diabetic patients with bilateral limbal stem cell deficiency. The present study aimed at assessing the possible effect of hemopoeitic stem cell (HSC) therapy on induced diabetic keratopathy in albino rat. METHODS AND RESULTS: Fifteen male albino rats were divided into control group of 2 rats, diabetic group of 8 rats receiving single intraperitoneal (IP) injection of 50 mg/kg streptozotocin (STZ). 3 animals were sacrificed 6 weeks following confirmation of diabetes to confirm keratopathy and 5 rats were sacrificed 4 weeks following confirmation of keratopathy. SC therapy group included 5 rats injected with HSCs 6 weeks following confirmation of diabetes and sacrificed 4 weeks following SC therapy. Cord blood collection, stem cells isolation and labeling were performed. Eye specimens were subjected to histological, histochemical, immunohistochemical, morphometric and statistical studies. In diabetic group, the central cornea showed multiple cells with vacuolated cytoplasm and dark nuclei, focal epithelial discontinuity, reduced corneal thickness and less number of layers of corneal and conjunctival epithelia. In stem cell therapy group, few cells with vacuolated cytoplasm and dark nuclei were found in the corneal and conjunctival epithelia with more number of epithelial layers. CONCLUSIONS: A definite ameliorating effect of HSC therapy was detected on diabetic keratopathy. The therapeutic cells were effective in limiting corneal epithelial changes.
Animals ; Apoptosis ; Cell Transplantation ; Cornea ; Cytoplasm ; Diabetes Mellitus, Type 2 ; Epithelium, Corneal ; Eye ; Fetal Blood ; Humans ; Insulin ; Male ; Necrosis ; Rats ; Statistics as Topic ; Stem Cells ; Streptozocin ; Transplants

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Evolution of Energy Metabolism, Stem Cells and Cancer Stem Cells: How the Warburg and Barker Hypotheses Might Be Linked.

James E TROSKO ; Kyung Sun KANG

International Journal of Stem Cells.2012;5(1):39-56.

The evolutionary transition from single cells to the metazoan forced the appearance of adult stem cells and a hypoxic niche, when oxygenation of the environment forced the appearance of oxidative phosphorylation from that of glycolysis. The prevailing paradigm in the cancer field is that cancers start from the "immortalization" or "re-programming" of a normal, differentiated cell with many mitochondria, that metabolize via oxidative phosphorylation. This paradigm has been challenged with one that assumes that the target cell for carcinogenesis is the normal, immortal adult stem cell, with few mitochondria. This adult organ-specific stem cell is blocked from "mortalizing" or from "programming" to be terminally differentiated. Two hypotheses have been offered to explain cancers, namely, the "stem cell theory" and the "de-differentiation" or "re-programming" theory. This Commentary postulates that the paleochemistry of the oceans, which, initially, provided conditions for life's energy to arise via glycolysis, changed to oxidative phosphorylation for life's processes. In doing so, stem cells evolved, within hypoxic niches, to protect the species germinal and somatic genomes. This Commentary provides support for the "stem cell theory", in that cancer cells, which, unlike differentiated cells, have few mitochondria and metabolize via glycolysis. The major argument against the "de-differentiation theory" is that, if re-programming of a differentiated cell to an "induced pluri-potent stem cell" happened in an adult, teratomas, rather than carcinomas, should be the result.
Adult ; Adult Stem Cells ; Energy Metabolism ; Genome ; Glycolysis ; Humans ; Mitochondria ; Oceans and Seas ; Oxidative Phosphorylation ; Oxygen ; Stem Cells ; Teratoma

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The Levels of Pro-Inflammatory Factors Are Significantly Decreased in Cerebral Palsy Patients Following an Allogeneic Umbilical Cord Blood Cell Transplant.

Sang Hun BAE ; Hyun Seob LEE ; Myung Seo KANG ; Barbara J STRUPP ; Michael CHOPP ; Jisook MOON

International Journal of Stem Cells.2012;5(1):31-38.

BACKGROUND AND OBJECTIVES: The transplantation of human umbilical cord blood cells (hUCBCs) has been shown to attenuate the unregulated activation of microglia in a rat model of cerebral palsy (CP). To investigate whether hUCBCs transplantation is also anti-inflammatory in humans, we performed a clinical trial in patients with CP. METHODS AND RESULTS: Allogeneic or autologous hUCBCs and erythropoietin (EPO) were intravenously injected into human patients with CP (mean age of approximately 38 weeks), and patients were analyzed for their motor function and social behavior. Blood samples were tested for cytokine levels. The most surprising finding in the study was that the cytokine levels were dependent on the donor cell source (allogeneic or autologous). Interestingly, the allogeneic treatment group demonstrated significantly decreased levels of pro-inflammatory factors, such as IL-1alpha, IL-6, TNF-beta, and RANTES, and showed a statistically significant improvement in motor and social behavior compared to the autologous treatment group. CONCLUSIONS: Given that inflammation plays a pivotal role in CP, our results suggest that allogeneic hUCBCs therapy may be an appropriate strategy for CP treatment. In addition, prior to transplantation, a detailed analysis of the amount of proinflammatory cytokines in cord blood may be needed to avoid exacerbating inflammatory responses.
Animals ; Cerebral Palsy ; Chemokine CCL5 ; Cytokines ; Erythropoietin ; Fetal Blood ; Humans ; Inflammation ; Interleukin-6 ; Lymphotoxin-alpha ; Microglia ; Rats ; Social Behavior ; Tissue Donors ; Transplants ; Umbilical Cord

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Long-term Angiogenesis Efficacy Using a Heparin-Conjugated Fibrin (HCF) Delivery System with HBM-MSCs.

Ae Kyeong KIM ; Min Hee KIM ; Byung Soo KIM ; Dong Ik KIM

International Journal of Stem Cells.2012;5(1):23-30.

BACKGROUND AND OBJECTIVES: Heparin-conjugated fibrin (HCF) is suitable for the release and localization of bFGF. We analyzed the effects of a bFGF delivery system using HCF with human bone marrow-derived mesenchymal stem cells (HBM- MSCs) in a dog ischemic limb model. METHODS AND RESULTS: Animals were divided into HBM-MSCs, HBM-MSCs+HCF, bFGF-HCF, and HBM-MSCs+bFGF-HCF groups. A total of 1x10(7) HBM-MSCs were injected per animal, and the amount of bFGF was 1 mg per dog. Ischemic muscles were harvested at eight weeks and six months after injection of cells. The HBM-MSCs+bFGF-HCF group exhibited decreased proportions of capillaries and arterioles six months after transplantation. However, there were more cells positive for the angiogenic factors, VEGF and PDGF, in the eight-week specimens compared with those harvested six months after transplantation. CONCLUSIONS: Our results demonstrated that a single injection of HBM-MSCs did not have significant long-term angiogenic effects; however, a bFGF delivery system using HCF exerted prolonged angiogenic effects when combined with HBM-MSCs.
Angiogenesis Inducing Agents ; Animals ; Arterioles ; Capillaries ; Dogs ; Extremities ; Fibrin ; Humans ; Ischemia ; Mesenchymal Stromal Cells ; Muscles ; Transplants ; Vascular Diseases ; Vascular Endothelial Growth Factor A

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Stimulation of Chondrogenic Differentiation of Mesenchymal Stem Cells.

Da Ae YU ; Jin HAN ; Byung Soo KIM

International Journal of Stem Cells.2012;5(1):16-22.

The methods for cartilage repair have been studied so far, yet many of them seem to have limitations due to the low regenerative capacity of articular cartilage. Mesenchymal stem cell (MSC) has been suggested as an alternative solution to remedy this challenging problem. MSCs, which have extensive differentiation capacity, can be induced to differentiate into chondrocytes under specific conditions. Particularly, this review focused on the effects of growth factors, cell-to-cell interactions and biomaterials in chondrogenesis of MSCs. Appropriate stimulations through these factors are crucial in differentiation and proliferation of MSCs. However, use of MSCs for cartilage repair has some drawbacks and risks, such as expression of hypertrophy-related genes in MSCs-derived chondrocytes and consequent calcification or cell death. Nevertheless, the clinical application of MSCs is expected in the future with advanced technology.
Biocompatible Materials ; Cartilage ; Cartilage, Articular ; Cell Communication ; Cell Death ; Chondrocytes ; Chondrogenesis ; Intercellular Signaling Peptides and Proteins ; Mesenchymal Stromal Cells

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