Placenta-Derived Mesenchymal Stem Cells Have an Immunomodulatory Effect That Can Control Acute Graft-Versus-Host Disease in Mice

Jang, Moon Ju; Kim, Hye‐Sun; Lee, Hye-Gyn; Kim, Gi Jin; Jeon, Hwang Gyun; Shin, Hyun‐Soo; Chang, Sung Woon; Hur, Gin-Hyung; Chong, So Young; Oh, Doyeun; Hong, Ki-Sung

doi:10.1159/000345267

Cited by 52 publications

(36 citation statements)

References 62 publications

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“…We isolated PD-MSCs and characterized them (Supplementary Figure 2) as previously described. 60 Briefly, the chorioamniotic membrane was peeled and separated from the placenta. Subsequently, the amnion and innermost membrane from the chorion and decidua were removed.…”

Section: Methodsmentioning

confidence: 99%

Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1–42-infused mouse model of Alzheimer’s disease

Kim

et al. 2013

Cell Death Dis

118

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Mesenchymal stem cells (MSCs) promote functional recoveries in pathological experimental models of central nervous system (CNS) and are currently being tested in clinical trials for neurological disorders, but preventive mechanisms of placenta-derived MSCs (PD-MSCs) for Alzheimer's disease are poorly understood. Herein, we investigated the inhibitory effect of PD-MSCs on neuronal cell death and memory impairment in Aβ1–42-infused mice. After intracerebroventrical (ICV) infusion of Aβ1–42 for 14 days, the cognitive function was assessed by the Morris water maze test and passive avoidance test. Our results showed that the transplantation of PD-MSCs into Aβ1–42-infused mice significantly improved cognitive impairment, and behavioral changes attenuated the expression of APP, BACE1, and Aβ, as well as the activity of β-secretase and γ-secretase. In addition, the activation of glia cells and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by the transplantation of PD-MSCs. Furthermore, we also found that PD-MSCs downregulated the release of inflammatory cytokines as well as prevented neuronal cell death and promoted neuronal cell differentiation from neuronal progenitor cells in Aβ1–42-infused mice. These data indicate that PD-MSC mediates neuroprotection by regulating neuronal death, neurogenesis, glia cell activation in hippocampus, and altering cytokine expression, suggesting a close link between the therapeutic effects of MSCs and the damaged CNS in Alzheimer's disease.

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Section: Methodsmentioning

confidence: 99%

Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1–42-infused mouse model of Alzheimer’s disease

Kim

et al. 2013

Cell Death Dis

118

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“…MSCs have therapeutic applications in multiple clinical disorders, including myocardial infarction, diabetes, sepsis, graft-versus-host disease, and hepatic and acute renal failure (1,7,14,26,31,33,39,53). Given the complex architecture of the lung, different cell therapy approaches have been implemented, including the use of 3D bioengineered and decellularized scaffolds populated with progenitor cells.…”

Section: Role Of Mscs In Lung Diseasementioning

confidence: 99%

MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

Sdrimas

Kourembanas

2014

Antioxidants & Redox Signaling

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Significance: Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of infancy, is a major complication of preterm birth that, despite improvements in neonatal respiratory support and perinatal care, remains an important cause of morbidity and mortality, often with severe adverse neurodevelopmental sequelae. Even with major advances in our understanding of the pathogenesis of this disease, BPD remains essentially without adequate treatment. Recent Advances: Cell-based therapies arose as a promising treatment for acute and chronic lung injury in many experimental models of disease. Currently, more than 3000 human clinical trials employing cell therapy for the treatment of diverse diseases, including cardiac, neurologic, immune, and respiratory conditions, are ongoing or completed. Among the treatments, mesenchymal stem cells (MSCs) are the most studied and have been extensively tested in experimental models of BPD, pulmonary hypertension, pulmonary fibrosis, and acute lung injury. Critical Issues: Despite the promising potential, MSC therapy for human lung disease still remains at an experimental stage and optimal transplantation conditions need to be determined. Although the mechanism of MSC action can be manifold, accumulating evidence suggests a predominant paracrine, immunomodulatory, and cytoprotective effect. Future Directions: The current review summarizes the effect of MSC treatment in models of lung injury, including BPD, and focuses on the MSC secretome and, specifically, MSC-derived microvesicles as potential key mediators of therapeutic action that can be the focus of future therapies. Antioxid. Redox Signal. 21, 1905Signal. 21, -1915

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“…In utero intervention allows clinicians to treat disease quickly after its onset and prevent debilitating symptoms before they ever occur [3,4] . Mesenchymal stromal cell (MSC) therapy can augment existing in utero surgical techniques, and treatment with MSCs has been shown to promote wound healing [5,6] , protect damaged tissues [7][8][9][10][11] , and modulate the immune system [12][13][14][15] . Cells obtained via methods such as chorionic villus sampling (CVS) allow for the potential development of cell therapies that are autologous (derived from the patient's cells) to the fetus [16][17][18] .…”

Section: Introductionmentioning

confidence: 99%

Early gestation chorionic villi-derived stromal cells for fetal tissue engineering

Lankford¹

2015

WJSC

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AIM:To investigate the potential for early gestation placenta-derived mesenchymal stromal cells (PMSCs) for fetal tissue engineering. METHODS:PMSCs were isolated from early gestation chorionic villus tissue by explant culture. Chorionic villus sampling (CVS)-size tissue samples (mean = 35.93 mg) were used to test the feasibility of obtaining large cell numbers from CVS within a clinically relevant timeframe. We characterized PMSCs isolated from 6 donor placentas by flow cytometry immunophenotyping, multipotency assays, and through immunofluorescent staining. Protein secretion from PMSCs was examined using two cytokine array assays capable of probing for over 70 factors in total. Delivery vehicle compatibility of PMSCs was determined using three common scaffold systems: fibrin glue, collagen hydrogel, and biodegradable nanofibrous scaffolds made from a combination of polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA). Viral transduction of PMSCs was performed using a Luciferase-GFPcontaining lentiviral vector and efficiency of transduction was tested by fluorescent microscopy and flow cytometry analysis. RESULTS:We determined that an average of 2.09 × 10 6 (SD ± 8.59 × 10 5 ) PMSCs could be obtained from CVS-size tissue samples within 30 d (mean = 27 d, SD ± 2.28), indicating that therapeutic numbers of cells can be rapidly expanded from very limited masses of tissue. Immunophenotyping by flow cytometry demonstrated that PMSCs were positive for MSC markers CD105, CD90, CD73, CD44, and CD29, and were negative for hematopoietic and endothelial markers CD45, CD34, and CD31. PMSCs displayed trilineage differentiation capability, and were found to express developmental transcription factors Sox10 and Sox17 as well as neuralrelated structural proteins NFM, Nestin, and S100β. Cytokine arrays revealed a robust and extensive profile of PMSC-secreted cytokines and growth factors, and detected 34 factors with spot density values exceeding 10 3 . Detected factors had widely diverse functions that include modulation of angiogenesis and immune response, cell chemotaxis, cell proliferation, blood vessel maturation and homeostasis, modulation of insulin-like growth factor activity, neuroprotection, extracellular matrix degradation and even blood coagulation. Importantly, PMSCs were also determined to be compatible with both Core tip: In this study we characterize mesenchymal stromal cells derived from early gestation human placenta chorionic villi (PMSCs) for the purpose of fetal tissue engineering. We examine cell expansion in early passages from chorionic villus sampling-size tissue samples, as well as PMSC surface marker expression, multipotency, intracellular protein expression, protein secretion, and compatibility with delivery vehicles and tracking methods often used for in vivo experimentation. We show that early gestation PMSCs are excellent candidates for future tissue engineering studies, particularly as it applies to in utero therapy for congenital anomalies.

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Placenta-Derived Mesenchymal Stem Cells Have an Immunomodulatory Effect That Can Control Acute Graft-Versus-Host Disease in Mice

Cited by 52 publications

References 62 publications

Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1–42-infused mouse model of Alzheimer’s disease

Placenta-derived mesenchymal stem cells improve memory dysfunction in an Aβ1–42-infused mouse model of Alzheimer’s disease

MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

Early gestation chorionic villi-derived stromal cells for fetal tissue engineering

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