Mesenchymal stem cells as anti-inflammatories: Implications for treatment of Duchenne muscular dystrophy

Ichim, Thomas E.; Alexandrescu, Doru T; Solano, Fabio; Lara, Fabian; Campion, Rosalia De Necochea; Paris, Eugenia; Woods, Erik J.; Murphy, Michael P.; Dasanu, Constantin A; Patel, Amit N.; Marleau, Annette M.; Leal, Alejandro; Riordan, Neil H

doi:10.1016/j.cellimm.2009.10.006

Cited by 152 publications

(131 citation statements)

References 142 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…In Duchenne muscular dystrophy, it has been hypothesized that MSC treatment may facilitate muscle cell repair via anti-inflammatory effects and production of soluble factors to stimulate production of endogenous stem cells in muscles. [36][37][38] Although several research groups have proposed various mechanisms for exertion of therapeutic effects of human MSC on some skeletal muscle diseases, any specific molecular mechanisms of human MSC protein secretion is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

Kwon

Park

et al. 2016

Molecular Therapy

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

Kwon

Park

et al. 2016

Molecular Therapy

View full text Add to dashboard Cite

“…The optical density [25] at 450 nm was read by a plate reader (DTX 880, Multimode detector, Beckman-Coulter). The raw data were normalized to a standard curve and used for calculation of total human IgG.…”

Section: Igg Quantification By Elisamentioning

confidence: 99%

Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro

et al. 2010

View full text Add to dashboard Cite

The capacity of mesenchymal stem cells (MSCs) to differentiate into intervertebral disc (IVD)-like cells has been well described, but their ability to modulate the inflammatory processes in the IVD remains unclear. We found that tissue obtained by discectomy of degenerated and post-traumatic IVD contains significant amounts of IgG antibodies, a sign of lymphocyte infiltration. Further we investigated whether MSCs in vitro, which were characterized for their multilineage differentiation potential and may have immunomodulatory effects on IVD fragments. IVD fragments were co-cultured in contact with peripheral blood lymphocytes (PBLs) and MSCs, and as functional controls we used contact co-cultures of PBLs stimulated with pokeweed mitogen (2.5 lg/mL) and MSCs. The time course of lymphocyte proliferation (Alamar Blue), IgG (ELISA) and gene expression (RT-PCR) of anti-inflammatory cytokines (TGF-b1, IL-10) by MSCs and proinflammatory molecules (IL-1a, IL-1b and TNF-a) by the IVD fragments were analyzed. Depending on the response to the presence of MSCs, the IVD fragments (n = 13) were divided in two groups: responders (n = 9), where inflammation was inhibited by MSCs and non-responders (n = 4), where MSCs did not decrease inflammation. At 1 week in co-culture, MSCs reduced significantly the IgG production in the IVD responders group to 69% and PBLs proliferation to 57% of the control. MSCs expression of the anti-inflammatory TGF-b1 increased with time, while IL-10 was expressed only at day 1. IVD gene expression of TNF-a decreased constantly, whereas IL-1a and IL-1b expression increased. In conclusion, these data suggest that MSCs may modulate disc-specific inflammatory and pain status and aid regeneration of the host tissue.

show abstract

“…Prednisone and deflazacort delay the loss of muscle strength and functionality, the loss of ambulation, the onset of scoliosis, and respiratory and cardiac failure. However, besides their positive role in inhibiting inflammatory pathways that cause muscle necrosis and fibrosis, corticosteroids have shown limited activity and cause several adverse effects such as gain of weight, reduction of bone mineral density, increased risk of bones fractures gastrointestinal irritation, skin fragility, adrenal suppression, susceptibility to infections, metabolic disorders, hypertension, behavioural changes, and cushingoid appearance [12][13][14][15]. Moreover, definitive evidence is lacking about the role of corticosteroids on muscle regeneration [16], and glucocorticoids exert anti-myogenic effects on myoblasts by inducing the expression of glucocorticoid-induced leucine zipper (GILZ) and its newly identified isoform, long GILZ (L-GILZ) [17].…”

Section: Corticosteroidsmentioning

confidence: 99%

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Chiappalupi

Salvadori

Luca

et al. 2017

JFMK

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is a lethal X-linked pathology due to lack of dystrophin and characterized by progressive muscle degeneration, impaired locomotion and premature death. The chronic presence of inflammatory cells, fibrosis and fat deposition are hallmarks of DMD muscle tissue. Many different therapeutic approaches to DMD have been tested, including cell-based and gene-based approaches, exon skipping, induction of expression of the dystrophin paralogue, utrophin, and, most recently the application of the CASPR/Cas9 genome editing system. However, corticosteroid treatment remains the gold standard therapy, even if corticosteroids have shown multiple undesirable side effects. Sertoli cells (SeC) have long been known for their ability to produce immunomodulatory and trophic factors, and have been used in a plethora of experimental models of disease. Recently, microencapsulated porcine SeC (MC-SeC) injected intraperitoneally in dystrophic mice produced morphological and functional benefits in muscles thanks to their release into the circulation of anti-inflammatory factors and heregulin β1, a known inducer of utrophin expression, thus opening a new avenue in the treatment of DMD. In order to stress the potentiality of the use of MC-SeC in the treatment of DMD, here, we examine the principal therapeutic approaches to DMD, and the properties of SeC (either nude or encapsulated into alginate-based microcapsules) and their preclinical and clinical use. Finally, we discuss the potential and future development of this latter approach.Keywords: Duchenne muscular dystrophy; therapeutic approaches; Sertoli cell; muscle inflammation; myopathies; encapsulation; biomaterials Duchenne Muscular Dystrophy (DMD)Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. Muscular dystrophies are a group of inherited muscle diseases characterized by mutations in specific genes and resulting in muscle degeneration, impaired locomotion and premature death [1,2]. DMD is an X-linked recessive pathology caused by mutations in the dystrophin gene (DMD) usually resulting in the complete absence of this protein. Dystrophin is an essential component of the dystrophin-associated protein complex (DAPC) at the sarcolemma, a complex that ensures the structural and functional integrity of the myofibers during contraction representing a mechanical link between the intracellular cytoskeleton and the extracellular matrix. Absence of dystrophin or other components of the DAPC compromises the integrity of the DAPC itself leading to a susceptibility of myofibers to degeneration

show abstract

Mesenchymal stem cells as anti-inflammatories: Implications for treatment of Duchenne muscular dystrophy

Cited by 152 publications

References 142 publications

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Contact Info

Product

Resources

About