Stem Cell Research & Therapy - Latest Articles

CD70-CD27 ligation between neural stem cells and CD4+ T cells induces Fas-FasL mediated T cell death

Eun Lee — 2013-05-21T00:00:00Z

IntroductionNeural stem cells (NSCs) are among the most promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. One of the remaining obstacles for NSCs therapy is to overcome the alloimmune response on NSCs by the host. Methods: To investigate the mechanisms of immune modulatory function derived from the interaction of human NSCs with allogeneic T cells, we examined the immune regulatory effects of human NSCs on allogeneic T cells in vitro. Results: Significantly, NSCs induced apoptosis of allogeneic T cells, in particular CD4+ T cells. Interaction of CD70 on NSCs and CD27 on CD4+ T cells mediated apoptosis of T cells. Thus, blocking CD70-CD27 interaction prevented NSCs-mediated death of CD4+ T cells. Conclusions: Here we present a rational explanation of NSCs-induced immune escape in two consecutive stages. First, CD70 constitutively expressed on NSCs engaged CD27 on CD4+ T cells, which induced FasL expression on CD4+ T cells. Second, CD4+ T cell apoptosis was followed by Fas-FasL interaction in the CD4+ T cells.

Human amniotic fluid- and dental pulp-derived stem cells seeded into collagen scaffold repair critical size bone defects promoting vascularization

Tullia Maraldi — 2013-05-21T00:00:00Z

IntroductionThe main aim of this study is to evaluate potential human stem cells, such as dental pulp stem cells (DPSC) and amniotic fluid stem cells (AFSC), combined with collagen scaffold, to reconstruct critical size cranial bone defects in animal model. Methods: We performed two symmetric full-thickness cranial defects on each parietal region of rats and we replenished them with collagen scaffolds with or without stem cells already seeded into and addressed towards osteogenic lineage in vitro. After 4 and 8 weeks cranial tissue samples were taken for histological and immunofluorescence analysis. Results: We observed a new bone formation in all the samples but the most relevant difference in defect correction were shown by stem cell-collagen samples at 4 weeks after implant, suggesting a faster regeneration ability of the combined constructs. The presence of human cells in the newly-formed bone was confirmed by confocal analysis with an antibody directed to a human mitochondrial protein. Furthermore, human cells were found to be an essential part of new vessel formation in the scaffold. Conclusions: All these data confirmed the strong potential of bioengineered constructs of stem cell-collagen scaffold for correcting large cranial defects in animal model and highlighting the role of stem cells in neo vascularization during skeletal defect reconstruction.

Endothelial microvascular networks affect gene expression profiles and osteogenic potential of tissue-engineered constructs

Torbjorn Pedersen — 2013-05-17T00:00:00Z

IntroductionA major determinant of the potential size of cell/scaffold constructs in tissue engineering is vascularization. The aims of this study were twofold: firstly to determine the in vitro angiogenic and osteogenic gene expression profiles of endothelial cells (EC) and mesenchymal stem cells (MSC) co-cultured in a dynamic 3D environment; and secondly, to assess differentiation and the potential for osteogenesis after in vivo implantation. Methods: MSC and EC were grown in dynamic culture in poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) copolymer scaffolds for 1 week, to generate three-dimensional endothelial microvascular networks. The constructs were then implanted in vivo, in a murine model for ectopic bone formation. Expression of selected genes for angiogenesis and osteogenesis were studied after 1 week's culture in vitro. Human cell proliferation was assessed as expression of ki67, whereas alpha-smooth muscle actin was used to determine the perivascular differentiation of MSC. Osteogenesis was evaluated in vivo through detection of selected markers, using real-time RT-PCR, alkaline phosphatase (ALP), Alizarin Red, HE and Masson's trichrome staining. Results: The results show that endothelial microvascular networks could be generated in a poly(LLA-co-DXO) scaffold in vitro, and sustained after in vivo implantation. The addition of EC to MSC influenced both angiogenic and osteogenic gene expression profiles. Furthermore, human ki67 was up-regulated before and after implantation. MSC could support functional blood vessels as perivascular cells independent of implanted EC. In addition, the expression of ALP was up-regulated in the presence of endothelial microvascular networks. Conclusions: This study demonstrates that copolymer poly(LLA-co-DXO) scaffolds can be prevascularized with EC and MSC. Although a local osteoinductive environment is required to achieve ectopic bone formation, seeding of MSC with or without EC increase the osteogenic potential of tissue-engineered constructs.

Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging

Faizal Asumda — 2013-05-14T00:00:00Z

Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient’s own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging.

Monitoring neurodegeneration in diabetes using adult neural stem cells derived from the olfactory bulb

Ryo Hidaka — 2013-05-14T00:00:00Z

IntroductionNeurons have the intrinsic capacity to produce insulin, similar to pancreatic cells. Adult neural stem cells (NSCs), which give rise to functional neurons, can be established and cultured not only by intracerebral collection, which requires difficult surgery, but also by collection from the olfactory bulb (OB), which is relatively easy. Adult neurogenesis in the hippocampus (HPC) is significantly decreased in diabetic patients. As a result, learning and memory functions, which the HPC is responsible for, decrease. Methods: In the present study, we compared the effect of diabetes on neurogenesis and insulin expression in adult NSCs. Adult NSCs were derived from the HPC or OB of streptozotocin-induced diabetic rats. Comparative gene expression analyses were carried out using extracted tissues and established adult NSC cultures from the HPC or OB in diabetic rats. Results: Diabetes progression influenced important genes that were required for insulin expression in both OB- and HPC-derived cells. Additionally, we found that the expression levels of several genes, such as voltage-gated sodium channels, glutamate transporters, and glutamate receptors, were significantly different in OB and HPC cells collected from diabetic rats. Conclusions: By using identified diabetes-response genes, OB NSCs from diabetes patients can be used to monitor processes during diabetes progression that cause neurodegeneration in the central nervous system (CNS). Since hippocampal NSCs and OB NSCs exhibited similar gene expression profiles during diabetes progression, OB NSCs, which are more easily collected and established than HPC NSCs, may potentially be used for screening of effective drugs for neurodegenerative disorders that cause malignant damage to CNS functions.

Vasculogenesis of decidua side population cells of first-trimester pregnancy

Qiushi Wang — 2013-05-07T00:00:00Z

IntroductionSufficient uterine blood supply is essential for the fetus to develop normally in the uterus. Several mechanisms are involved in the process of vessel development in deciduas and villus. We focus on whether first-trimester decidua side population cells contain cells capable of differentiating into endothelial cells. Methods: Eight decidua samples were collected from healthy women aged 22 to 30 years undergoing elective terminations of early pregnancy (6 to 8 gestational weeks). The cell suspensions from human deciduas were stained by Hoechst 33342 and sorted by flow cytometry, further cultured under differentiation conditions and analyzed for specific markers. These cells were implanted into ischemic limbs of nude mice to test the capacity of angiogenesis in vivo by DiI tracers and immunohistochemistry. Results: Decidua CD31-CD146- side population (SP) cells of first-trimester human pregnancy can differentiate into endothelial cells, express the corresponding specific markers of endothelial cells, such as CD31 and CD146, and form tube-like structures on Matrigel and part of newly formed vessels in the ischemic limb of nude mice. Vascular endothelial growth factor (VEGF) was more effective in promoting proliferation of CD31-CD146-SP cells compared with other growth factors, and estrogen and progesterone at the final concentration of 10mumol/L and 30mumol/L promoted the migration of CD31-CD146-SP cells in a dose-dependent manner. Conclusions: CD31-CD146- SP cells may be involved in formation of new vessels in the maternal aspect of placenta in the first trimester.

Therapeutic implications of mesenchymal stem cells in acute lung injury/acute respiratory distress syndrome

Yan Yang Wang — 2013-05-02T00:00:00Z

Acute lung injury (ALI), and its more severe form, acute respiratory distress syndrome (ARDS), are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. Current treatment of ALI/ARDS is primarily supportive, with lung protective ventilation and fluid conserving strategies. Despite improvement in these strategies, recent data indicate that the mortality of ALI/ARDS is still as high as 30 to 50%. Thus, there is a need for innovative therapies to further improve clinical outcomes of ALI/ARDS. Recent studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI/ARDS have shown promising results. This review focuses on existing studies that have tested the use of MSCs in models of ALI/ARDS, and the potential mechanisms underlying their therapeutic effects.

Three years of Stem Cell Research & Therapy

Philippa Locke — 2013-05-01T00:00:00Z

No description available

The characteristic expression pattern of BMI-1 and SALL4 genes in placenta tissue and cord blood

Shaohua Chen — 2013-04-30T00:00:00Z

IntroductionSALL4 and BMI-1 are important factors in hematopoiesis. Placental tissue (PT) and umbilical cord blood (CB) are rich in hematopoietic stem/progenitor cells (HSCs/HPCs), but their SALL4 and BMI-1 expression levels remain unknown. Methods: Real-time PCR was used to determine the expression level of these genes in PT and CB from ten cases, and ten healthy donors were used as controls. Results: A significantly higher BMI-1 and SALL4 gene expression level was found in PT (median: 17.548 and 34.362, respectively) than in cord blood mononuclear cells (CBMCs) (median: 2.071 and 11.300, respectively) (P = 0.0001 and P = 0.007) and healthy peripheral blood mononuclear cells (PBMCs) (median: 0.259 and 0.384, respectively) (P = 0.001 and P <0.0001), and their expression level was lower in PBMCs than in CBMCs (P = 0.029 and P = 0.002). A positive correlation between the BMI-1 and SALL4 genes was found in the PT and CB groups, while there was no significant correlation between these genes in the healthy group. There was also no significant correlation between the expression level of each gene in PT and CB. Conclusions: These results describe the characteristic features of the BMI-1 and SALL4 gene expression pattern in placental tissue and cord blood. Placental tissue with higher expression level of both genes may be considered as a potential resource for SALL4-related HPC expansion.

Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

Jessica Quimby — 2013-04-30T00:00:00Z

IntroductionAdministration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD. Methods: Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 106 cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 106 cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 106 aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction. Results: Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3. Conclusions: Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters.