Biotherapies developed and manufactured in France in compliance with good practices
Clinical studies based on real animal treatments
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Biotherapies developed and manufactured in France in compliance with good practices
Clinical studies based on real animal treatments
Easy to use products, delivered solely by veterinarians
Précédent
Suivant

18 – Pro-Inflammatory Cytokines, IFN and TNF, Influence Immune Properties of Human Bone Marrow and Wharton Jelly Mesenchymal Stem Cells Differentially.

Prasanna SJ, Gopalakrishnan D, Shankar SR, Vasandan AB. PLOS ONE. 2010.

Background: Wharton's jelly derived stem cells (WJMSCs) are gaining attention as a possible clinical alternative to bone marrow derived mesenchymal stem cells (BMMSCs) owing to better accessibility, higher expansion potential and low immunogenicity. Usage of allogenic mesenchymal stem cells (MSC) could be permissible in vivo only if they retain their immune properties in an inflammatory setting. Thus the focus of this study is to understand and compare the immune properties of BMMSCs and WJMSCs primed with key pro-inflammatory cytokines, Interferon-gamma (IFNgamma) and Tumor Necrosis Factor-alpha (TNFalpha).

Methodology/principal findings: Initially the effect of priming on MSC mediated suppression of alloantigen and mitogen induced lymphoproliferation was evaluated in vitro. Treatment with IFNgamma or TNFalpha, did not ablate the immune-suppression caused by both the MSCs. Extent of immune-suppression was more with WJMSCs than BMMSCs in both the cases. Surprisingly, priming BMMSCs enhanced suppression of mitogen driven lymphoproliferation only; whereas IFNgamma primed WJMSCs were better suppressors of MLRs. Further, kinetic analysis of cytokine profiles in co-cultures of primed/unprimed MSCs and Phytohematoagglutinin (PHA) activated lymphocytes was evaluated. Results indicated a decrease in levels of pro-inflammatory cytokines. Interestingly, a change in kinetics and thresholds of Interleukin-2 (IL-2) secretion was observed only with BMMSCs. Analysis of activation markers on PHA-stimulated lymphocytes indicated different expression patterns in co-cultures of primed/unprimed WJMSCs and BMMSCs. Strikingly, co-culture with WJMSCs resulted in an early activation of a negative co-stimulatory molecule, CTLA4, which was not evident with BMMSCs. A screen for immune suppressive factors in primed/unprimed WJMSCs and BMMSCs indicated inherent differences in IFNgamma inducible Indoleamine 2, 3-dioxygenase (IDO) activity, Hepatocyte growth factor (HGF) and Prostaglandin E-2 (PGE2) levels which could possibly influence the mechanism of immune-modulation.

Conclusion / Significance This study demonstrates that inflammation affects the immune properties of MSCs distinctly. Importantly different tissue derived MSCs could utilize unique mechanisms of immune-modulation.

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Product Pipeline

Range Product Development & optimization Proof of Concept Pilot study Industrialisation /
Manufacturing
Pivotal study Approval Marketing Launch

CANIPREN

VBX-01
Canine osteoarthritis

CA0102
Atopic dermatitis

CA0103
Atopic dermatitis
Chronic
Inflammatory
Bowel
Disease

Range Product Development & optimization Proof of Concept Pilot study Industrialisation /
Manufacturing
Pivotal study Approval Marketing Launch

FELIPREN

FE0101
Gingivostomatitis

FE0102
Chronic kidney
failure

FE0103
Feline arthrosis

Range Product Development & optimization Proof of Concept Pilot study Industrialisation /
Manufacturing
Pivotal study Approval Marketing Launch

EQUIPREN
OMBISTEM

EQ0101
Equine arthrosis