Combined therapy of mesenchymal stem cells with a GLP-1 receptor agonist, liraglutide, on an inflammatory-mediated diabetic non-human primate model

Rheumatoid arthritis (RA) is a disorder triggered by autoimmune reactions and related with chronic inflammation and severe disability. Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) have shown a hopeful immunomodulatory effect towards repairing cartilage and restoring joint function. Additionally, indomethacin (IMC), a nonsteroidal compound, has been considered as a potent therapeutic agent that exhibits significant antipyretic properties and analgesic effects. The target of the current research is to assess the antiarthritic efficacy of BM-MSCs (106 cells/rat at 1, 6, 12 and 18 days) and IMC (2 mg/kg body weight/day for 3 weeks) either alone or concurrently administered against complete Freund’s adjuvant-induced arthritic rats. Changes in paw volume, body weight, gross lesions, and antioxidant defense system, as well as oxidative stress, were assessed. The Th1 cytokine (IL-1β) serum level and Th2 cytokine (IL-4) and Nrf-2 ankle joint expression were detected. In comparison to normal rats, it was found that the CFA-induced arthritic rats exhibited significant leukocytosis and increase in paw volume, LPO level, RF, and IL-1β serum levels. In parallel, arthritic rats that received BM-MSCs and/or IMC efficiently exhibited decrease in paw edema, leukocytosis, and enhancement in the antioxidant enzymatic levels of SOD, GPx, GST, and GSH in serum besides upregulation of Nrf-2 and anti-inflammatory IL-4 expression levels in the ankle articular joint. Likewise, these analyses were more evidenced by the histopathological sections and histological score. The data also revealed that the combined administration of BM-MSC and IMC was more potent in suppressing inflammation and enhancing the anti-inflammatory pathway than each agent alone. Thus, it can be concluded that the combined therapy with BM-MSC and IMC may be used as a promising therapeutic choice after assessing their efficacy and safety in human beings with RA, and the antiarthritic effects may be mediated via modulatory effects on Th1/Th2 cytokines, ozidative stress, and Nrf-2.

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Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto

Journal of Biomedical Science ◽

10.1186/1423-0127-16-75 ◽

2009 ◽

Vol 16 (1) ◽

pp. 75 ◽

Cited By ~ 32

Author(s):

Hung-Chuan Pan ◽

Dar-Yu Yang ◽

Shu-Peng Ho ◽

Meei-Ling Sheu ◽

Chung-Jung Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Sciatic Nerve ◽

Amniotic Fluid ◽

Combined Therapy ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Human Amniotic Fluid ◽

Nerve Crush ◽

Nerve Crush Injury

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1982 Influence of mobilized stem cells on myocardial infarct repair in a non-human primate model of acute myocardial infarction

European Heart Journal ◽

10.1016/s0195-668x(03)95007-x ◽

2003 ◽

Vol 24 (5) ◽

pp. 366 ◽

Cited By ~ 1

Author(s):

F NOROL

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stem Cells ◽

Myocardial Infarct ◽

Primate Model ◽

Human Primate

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Hedgehog Signaling and Hematopoiesis Regulation: Preliminary Study in Myelosuppressed Adult Non Human Primate model.

Blood ◽

10.1182/blood.v114.22.4603.4603 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4603-4603

Author(s):

Michel Drouet ◽

Philippe Garrigou ◽

Nancy Grenier ◽

Christophe Delaunay ◽

Jean-François Mayol ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hedgehog Signaling ◽

Conflicts Of Interest ◽

Short Term ◽

Primate Model ◽

Hematopoietic Stem ◽

Cell Counts ◽

Therapy Strategy ◽

Human Primate

Abstract Abstract 4603 The precise role of hedgehog signaling (Shh) in adult hematopoiesis is still debated. One one hand its implication in differentiation and proliferation of hematopoietic stem cells has been reported by different teams. Thus Bhatia et al showed using an immunocompromized mouse model that Shh allows in vitro amplification of CD34+/38- pool. Shh may be especially invoved in megakaryocytopoiesis. In addition transgenic mice (ptc1/-) exhibiting an increased Shh activity has been shown to recover more rapidly than controls following myelosuppression and prolonged Shh stimulation appeared to deplete the stem cell pool due to cell cycle acceleration. On the other hand, recent studies also suggest that hedgehog signaling could be dispensable for adult hematopoieisis (Hoffmann-Zhang, Blood 2008 abstr 1391. The goal of this study was to set up an adult non human primate model to clarify some of these points. We chose a gene therapy strategy based on short term expression of Shh in bone marrow of highly irradiated monkeys (efficient stimulation and reduction of side effects). We first demonstrated the feasibility of transducing multipotent fibroblastic stem cells as vector cells using a piRES-2-Shh-eGFP plasmid and Nucleofector technology (Amaxa). As bone marrow nonhuman primate mesenchymal stem cells are known to be frequently contaminated by retroviruses, we used adipocyte derived stem cells as vector cells. In this model, Shh protein was detected during 5 days in the transduced cells and was secreted during 3 days in accordance with our short term secretion model. Then Shh-ASC were injected to rhesus monkeys the day after a global and frontal irradiation at the dose of 8Gy 60Co gamma. At this dose, monkeys exhibited a severe and prolonged neutropenia and thrombocytopenia allowing us to evaluate the therapeutic benefit of the grafts. In a first grafted monkey (9kg), 2×106 Shh-ASC (about 43% GFP positive cells) were injected in the femur. Blood cell counts did not significantly differ from irradiated control animals (n=4). Further experiments will contribute to determine whether Hedgehog signaling is involved in adult primate recovery following myelosuppression. Disclosures: No relevant conflicts of interest to declare.

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