Journal Detail Information

1

Cite

Share

Direct Differentiation of Adult Ocular Progenitors into Striatal Dopaminergic Neurons.

Iqbal AHMAD ; Xing ZHAO ; Sowmya PARAMESWARAN ; Christopher J DESTACHE ; Jorge RODRIGUEZ-SIERRA ; Wallace B THORESON ; Hiba AHMAD ; John SORRENTINO ; Sudha BALASUBRAMANIAN

International Journal of Stem Cells.2015;8(1):106-114. doi:10.15283/ijsc.2015.8.1.106

Parkinson's disease, characterized by motor dysfunction due to the loss of nigrostriatal dopaminergic neurons, is one of the most prevalent age-related neurodegenerative disorders. Given there is no current cure, the stem cell approach has emerged as a viable therapeutic option to replace the dopaminergic neurons that are progressively lost to the disease. The success of the approach is likely to depend upon accessible, renewable, immune compatible, and non-tumorigenic sources of neural progenitors from which stable dopaminergic neurons can be generated efficaciously. Here, we demonstrate that neural progenitors derived from limbus, a regenerative and accessible ocular tissue, represent a safe source of dopaminergic neurons. When the limbus-derived neural progenitors were subjected to a well-established protocol of directed differentiation under the influence of Shh and FGF8, they acquired the biochemical and functional phenotype of dopaminergic neurons that included the ability to synthesize dopamine. Their intrastriatal transplantation in the rat model of hemi-Parkinsonism was associated with a reduction in the amphetamine-induced rotation. No tumor formation was observed 6 weeks post-transplantation. Together, these observations posit limbus-derived neural progenitors as an accessible and safe source of dopaminergic neurons for a potential autologous ex-vivo stem cell approach to Parkinson's disease.
Adult* ; Dopamine ; Dopaminergic Neurons* ; Humans ; Models, Animal ; Neurodegenerative Diseases ; Parkinson Disease ; Phenotype ; Stem Cells

2

Cite

Share

Combination Cell Therapy with Mesenchymal Stem Cells and Neural Stem Cells for Brain Stroke in Rats.

Seyed Mojtaba HOSSEINI ; Mohammad FARAHMANDNIA ; Zahra RAZI ; Somayeh DELAVARI ; Benafsheh SHAKIBAJAHROMI ; Fatemeh Sabet SARVESTANI ; Sepehr KAZEMI ; Maryam SEMSAR

International Journal of Stem Cells.2015;8(1):99-105. doi:10.15283/ijsc.2015.8.1.99

OBJECTIVES: Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. METHOD AND MATERIALS: The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. RESULT: The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. CONCLUSIONS: The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.
Adult ; Animals ; Bone Marrow ; Brain* ; Caspase 3 ; Cell- and Tissue-Based Therapy* ; Central Nervous System ; Embryonic Structures ; Ganglion Cysts ; Humans ; Infarction, Middle Cerebral Artery ; Mesenchymal Stromal Cells* ; Neural Stem Cells* ; Neurologic Examination ; Rats* ; Stroke*

3

Cite

Share

Attachment and Differentiation of Human Umbilical Cord Stem Cells on to the Tooth Root Surface with and without the Use of Fibroblast Growth Factor-An In Vitro Study.

Joann Pauline GEORGE ; Pornika CHAKRAVARTY ; Kamedh Yashawant CHOWDHARY ; H PURUSHOTHAMA ; Jyothsna A RAO

International Journal of Stem Cells.2015;8(1):90-98. doi:10.15283/ijsc.2015.8.1.90

BACKGROUND AND OBJECTIVES: The purpose of this first of its kind study was to analyse the growth, development and attachment of cultured human umbilical cord stem cells alone or supplemented with basic Fibroblast Growth Factor (bFGF) on both healthy and periodontally diseased tooth surfaces in vitro. METHODS: Four groups of 12 root surface scaffolds each were classified as Group I- healthy root surfaces; Group II- periodontally diseased; Group III- Healthy with bFGF and Group IV- periodontally diseased root with bFGF. bFGF was applied in the concentration of 8 ng/ml on to the surface followed by incubation of cultured human umbilical cord stem cells (hUCMSCs) on the scaffolds. Scanning electron microscopy observations were made on 14th and 21st days to assess the proliferation and morphology of cells attached on the tooth surface. RESULTS: Cultured hUCMSCs demonstrated adhesion to tooth root scaffold. All the groups showed a significant increase in the number of cell attachment from 14th day to 21st day. The groups with bFGF showed a significant increase in attachment of cells when compared to the groups without bFGF. The cells showed an increase in number of flat cells from 14th day to 21st day in all the groups indicating an increased maturity of cells. Periodontally diseased groups had less maturity of cells than healthy groups. The groups supplemented with bFGF, had more mature cells than the groups without bFGF. CONCLUSIONS: hUCMSCs have the propensity to differentiate into cells that have the capacity to bind to root surfaces. hUCMSCs incubated with bFGF showed better proliferation and attachment to tooth root surfaces. The role of hUCMSCs can be further explored for periodontal regeneration.
Fibroblast Growth Factor 2 ; Fibroblasts* ; Humans ; Intercellular Signaling Peptides and Proteins ; Mesenchymal Stromal Cells ; Microscopy, Electron, Scanning ; Regeneration ; Stem Cells* ; Tooth ; Tooth Root* ; Umbilical Cord*

4

Cite

Share

Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury.

Jieun JUNG ; Ji Wook MOON ; Jong Ho CHOI ; Yong Woo LEE ; Sun Hwa PARK ; Gi Jin KIM

International Journal of Stem Cells.2015;8(1):79-89. doi:10.15283/ijsc.2015.8.1.79

BACKGROUND: Human chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from the placenta have been reported to demonstrate therapeutic effects in animal models of liver injury; however, the underlying epigenetic mechanism of this effect has not been elucidated. Thus, we investigated whether CP-MSCs influence epigenetic processes during regeneration of the injured liver. METHODS: CP-MSCs were engrafted into a carbon tetrachloride (CCl4)-injured rat model through direct transplantation into the liver (DTX), intrasplenic transplantation (STX), and intravenous transplantation via the tail vein (TTX). Non-transplanted (NTX) rats were maintained as sham controls. Liver tissues were analyzed after transplantation using immunohistochemistry, western blot analysis, and quantitative methylation-specific polymerase chain reaction. Proliferation and human interleukin-6 (hIL-6) enzyme-linked immunosorbent assays were performed using CCl4-treated hepatic cells that were co-cultured with CP-MSCs. RESULTS: The Ki67 labeling index, cell cyclins, albumin, IL-6, and gp130 levels were elevated in the CP-MSC transplantation groups. The concentration of hIL-6 in supernatants and the proliferation of CCl4-treated rat hepatic cells were enhanced by co-culturing with CP-MSCs (p<0.05), while the methylation of IL-6/IL-6R and STAT3 by CP-MSC transplantation decreased. CONCLUSION: These results suggest that administration of CP-MSCs promotes IL-6/STAT3 signaling by decreasing the methylation of the IL-6/SATA3 promoters and thus inducing the proliferation of hepatic cells in a CCl4-injured liver rat model. These data advance our understanding of the therapeutic mechanisms in injured livers, and can facilitate the development of cell-based therapies using placenta-derived stem cells.
Animals ; Blotting, Western ; Carbon Tetrachloride ; Chorion ; Cyclins ; DNA Methylation ; Enzyme-Linked Immunosorbent Assay ; Epigenesis, Genetic ; Epigenomics* ; Hepatocytes ; Humans ; Immunohistochemistry ; Interleukin-6 ; Liver Regeneration ; Liver* ; Mesenchymal Stromal Cells ; Methylation ; Models, Animal* ; Placenta ; Polymerase Chain Reaction ; Rats ; Regeneration* ; Stem Cells* ; Veins

5

Cite

Share

Bone Marrow Mesenchymal Stem Cell Transplantation in a Rabbit Corneal Alkali Burn Model (A Histological and Immune Histo-chemical Study).

Soheir Kamal AHMED ; Amel Ali SOLIMAN ; Sahar M M OMAR ; Wafaa Rabee MOHAMMED

International Journal of Stem Cells.2015;8(1):69-78. doi:10.15283/ijsc.2015.8.1.69

BACKGROUND: Alkali-burned corneas can seldom heal properly to restore corneal transparency. Treatment of this severe disorder of the ocular surface remains a challenge. AIM OF THE WORK: was to investigate whether systemically transplanted bone marrow mesenchymal stem cells (BM-MSCs) can promote corneal wound healing after alkali burn. MATERIAL AND METHODS: Thirty five male New Zealand rabbits were used in this study. The animals were divided into three groups. Group I; the control group was sham operated. Group II; corneal alkali burn was created. Group III; underwent corneal alkali burn then treated with BM-MSCs. All corneas were collected after fourteen and twenty eight days. Evaluation using H&E, PAS & alkaline phosphatase reaction was carried out. Immune histo-chemical staining for CD44 and vimentin was performed as well. RESULTS: the corneal epithelium of (Group II) showed marked alterations. Vascularization, cellular infiltration and irregularity of the collagen fibers were also seen in the substantia propria. Increase in the thickness of the Descemet's membrane was noticed as well. On the other hand, at the time of 28 days, Group III rabbits showed best histological results with nearly healed corneas compared to other groups. Meanwhile, vimentin was more strongly expressed in Group III assessing the differentiating ability of BM-MSCs. CONCLUSION: BM-MSCs could effectively promote corneal alkali burn healing.
Alkalies* ; Alkaline Phosphatase ; Animals ; Bone Marrow* ; Burns* ; Collagen ; Cornea ; Descemet Membrane ; Epithelium, Corneal ; Hand ; Humans ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells ; Rabbits ; Vimentin ; Wound Healing

6

Cite

Share

New Strategies for Overcoming Limitations of Mesenchymal Stem Cell-Based Immune Modulation.

Nayoun KIM ; Seok Goo CHO

International Journal of Stem Cells.2015;8(1):54-68. doi:10.15283/ijsc.2015.8.1.54

Mesenchymal stem cells (MSCs) have rapidly been applied in a broad field of immune-mediated disorders since the first successful clinical use of MSCs for treatment of graft-versus-host disease. Despite the lack of supporting data, expectations that MSCs could potentially treat most inflammatory conditions led to rushed application and development of commercialized products. Today, both pre-clinical and clinical studies present mixed results for MSC therapy and the discrepancy between expected and actual efficacy of MSCs in various diseases has evoked a sense of discouragement. Therefore, we believe that MSC therapy may now be at a critical milestone for re-evaluation and re-consideration. In this review, we summarize the current status of MSC-based clinical trials and focus on the discrepancy between expected and actual outcome of MSC therapy from bench to bedside. Importantly, we discuss the underlying limitations of MSCs and suggest a new guideline for MSC therapy in hopes of improving their therapeutic efficacy.
Graft vs Host Disease ; Hope ; Mesenchymal Stromal Cells

7

Cite

Share

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration.

Rodrigo MARDONES ; Claudio M JOFRE ; Jose J MINGUELL

International Journal of Stem Cells.2015;8(1):48-53. doi:10.15283/ijsc.2015.8.1.48

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an \'in situ' cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed.
Cartilage* ; Cartilage, Articular ; Cell- and Tissue-Based Therapy* ; Chondrocytes ; Cytokines ; Diffusion ; Extracellular Matrix ; Intercellular Signaling Peptides and Proteins ; Joints ; Mesenchymal Stromal Cells ; Osteoarthritis ; Phenotype ; Regeneration* ; Synovial Fluid ; Tissue Engineering*

8

Cite

Share

Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation.

Soo Young LEE ; Han Joon KIM ; Dongho CHOI

International Journal of Stem Cells.2015;8(1):36-47. doi:10.15283/ijsc.2015.8.1.36

The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells.
Adult ; Bioprinting ; Extracellular Matrix ; Hepatocytes ; Humans ; Incidence ; Liver Diseases ; Liver Transplantation* ; Liver* ; Liver, Artificial ; Regenerative Medicine ; Stem Cell Research ; Stem Cells ; Tissue Donors ; Tissue Engineering*

9

Cite

Share

Regulation of Stem Cell Fate by ROS-mediated Alteration of Metabolism.

Jung Min RYU ; Hyun Jik LEE ; Young Hyun JUNG ; Ki Hoon LEE ; Dah Ihm KIM ; Jeong Yeon KIM ; So Hee KO ; Gee Euhn CHOI ; Ing Ing CHAI ; Eun Ju SONG ; Ji Young OH ; Sei Jung LEE ; Ho Jae HAN

International Journal of Stem Cells.2015;8(1):24-35. doi:10.15283/ijsc.2015.8.1.24

Stem cells have attracted much attention due to their distinct features that support infinite self-renewal and differentiation into the cellular derivatives of three lineages. Recent studies have suggested that many stem cells both embryonic and adult stem cells reside in a specialized niche defined by hypoxic condition. In this respect, distinguishing functional differences arising from the oxygen concentration is important in understanding the nature of stem cells and in controlling stem cell fate for therapeutic purposes. ROS act as cellular signaling molecules involved in the propagation of signaling and the translation of environmental cues into cellular responses to maintain cellular homeostasis, which is mediated by the coordination of various cellular processes, and to adapt cellular activity to available bioenergetic sources. Thus, in this review, we describe the physiological role of ROS in stem cell fate and its effect on the metabolic regulation of stem cells.
Adult Stem Cells ; Cues ; Energy Metabolism ; Glucose ; Homeostasis ; Metabolism* ; Oxygen ; Reactive Oxygen Species ; Stem Cells*

10

Cite

Share

Hormonal Regulation of Hematopoietic Stem Cells and Their Niche: A Focus on Estrogen.

Hye Ryeon HEO ; Li CHEN ; Borim AN ; Kye Seong KIM ; Junfeng JI ; Seok Ho HONG

International Journal of Stem Cells.2015;8(1):18-23. doi:10.15283/ijsc.2015.8.1.18

Self-renewal and differentiation are hallmarks of stem cells and controlled by various intrinsic and extrinsic factors. Increasing evidence indicates that estrogen (E2), the primary female sex hormone, is involved in regulating the proliferation and lineage commitment of adult and pluripotent stem cells as well as modulating the stem cell niche. Thus, a detailed understanding of the role of E2 in behavior of stem cells may help to improve their therapeutic potential. Recently, it has been reported that E2 promotes cell cycle activity of hematopoietic stem and progenitor cells and induces them to megakaryocyte-erythroid progenitors during pregnancy. This study paves the way towards a previously unexplored endocrine mechanism that controls stem cell behavior. In this review, we will focus on the scientific findings regarding the regulatory effects of E2 on the hematopoietic system including its microenvironment.
Adult ; Cell Cycle ; Estrogens* ; Female ; Hematopoiesis ; Hematopoietic Stem Cells* ; Hematopoietic System ; Humans ; Megakaryocyte-Erythroid Progenitor Cells ; Pluripotent Stem Cells ; Pregnancy ; Stem Cell Niche ; Stem Cells

DISPLAY OPTIONS

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share