Immune Modulation by Mesenchymal Stem Cells

Bifari, Francesco; Lisi, Veronica; Mimiola, Elda; Pasini, Anna Fratta; Krampera, Mauro

doi:10.1159/000128968

Cited by 48 publications

(42 citation statements)

References 129 publications

(286 reference statements)

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“…vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)) [10]. These factors are biologically active, modify local immunological responses, affect the formation of fibrosis, and promote the differentiation and proliferation of myofibers [11,12,13,14]. In particular the IGF family has been shown to be a key factor in muscular regeneration.…”

Section: Introductionmentioning

confidence: 99%

Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

Roth

Winkler

Rechenbach

et al. 2013

Transfus Med Hemother

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SummaryBackground: Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Previous investigation could show the efficacy of a local transplantation (TX) of mesenchymal stroma cells (MSCs) for the therapy of muscle injury. Underlying mechanisms remain to be elucidated. The aim of the present work was to characterize the fiber composition changes following MSC-TX after open crush injury. Methods: 20 male SD rats received an open crush trauma of the left soleus muscle. 2.5 × 10⁶ autologous MSCs were transplanted into the crushed soleus muscle of 10 animals 7 days after trauma (group 1, n = 10). Control animals received an injection of saline solution (group 2, n = 10). Histologic analysis of fibrosis, fiber type composition, and muscle force measurements were performed 28 days after trauma. Results: MSC-TX improved muscle force significantly (fast-twitch, treated: 0.76 (0.51-1.15), untreated: 0.45 (0.32-0.73); p = 0.01). Tetanic stimulation resulted in a significant increase of force development (treated: 0.63 (0.4-1.21), untreated: 0.34 (0.16-0.48); p = 0.04). Histological analyses showed no differences in the amount of fibrotic tissue (treated vs. untreated, p = 0.42). A shift towards fastMHC-positive fibers was observed following MSC-TX (treated vs. untreated; p = 0.01 (mm²) or 0.007 (%)). Conclusion: This study demonstrated an effect of locally administered MSCs in the treatment of skeletal muscle injuries on a structural level. For the first time a fiber type shift towards fastMHC following MSC-TX after crush injury could be demonstrated and related to MSC-TX. These results might open the discussion of an alternative mode of action of MSCs in tissue regeneration.

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Section: Introductionmentioning

confidence: 99%

Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

Roth

Winkler

Rechenbach

et al. 2013

Transfus Med Hemother

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“…In contrast to an expected induction of T cell response against allogeneic MSCs, T cell alloreactivity is inhibited by MSCs in mixed lymphocyte cultures (MLC) or lymphocyte proliferation induced by mitogens, such as phytohemagglutinin (PHA) or concanavalin A [7,12]. Remarkably, MSCs in high concentrations (representing 10-40 MSCs per 100 responder lymphocytes) inhibit, while low MSC concentrations (0.1-1%) may stimulate lymphocyte proliferation in MLC [90].…”

Section: Immunomodulatory Capacities Of Mscsmentioning

confidence: 96%

“…they stand out due to their extensive expansion potential and their broad, mesodermal differentiation as well as their immunomodulatory capabilities [9][10][11][12][13]. These features have led to their clinical exploitation in numerous clinical trials (www.clinicaltrials.gov).…”

mentioning

confidence: 99%

Clinical Protocols for the Isolation and Expansion of Mesenchymal Stromal Cells

Schallmoser

Klüter²,

Strunk

2008

Transfus Med Hemother

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“…28 They secrete angiogenic factors and promote angiogenesis thus reversing hypoxia of the brain. 29 This improves blood supply and oxygenation to the brain.…”

mentioning

confidence: 99%

A Case of Autism Showing Clinical Improvements after Cellular Therapy along with PET CT Evidence

Sharma

Gokulch

Sane

et al. 2017

JSRT

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On the Indian Scale for Assessment of Autism (ISAA), his score was 98, while his Childhood Autism Rating Scale (CARS) and Functional Independence Measure (WeeFIM) scores were 28.5 (ASD) and 80, respectively. MRI of the brain and EEG were normal. PET CT scan of the brain revealed hypometabolism in the bilateral cerebellar hemispheres and hypermetabolism in frontal, parietal and temporal lobes. AbstractAutism is a complex neurodevelopmental disorder defined by a triad of deficits including impaired social interaction, communication and behaviour. With greater understanding of mechanism of action of cellular therapy it is now possible to address the pathology of autism. Here is a case of a six and a half year old boy with autism who was administered autologous bone marrow mononuclear cells (BMMNCs) intrathecally followed by an intensive rehabilitation program. On follow up at 3months and 7months post intervention, he showed significant symptomatic improvements with no major side effects. At the end of 7months, ISAA score improved from 98 to 81. The Wee FIM showed improvement 80 to 89.1. CARS score reduced from 28.5 (mild to moderate autism) to 23.5 (mild autism). PET CT scan of the brain performed pre intervention and seven months post showed a balancing effect in the metabolism of affected areas. It also showed reduction in hypermetabolism of the frontal, parietal and temporal lobe bilaterally and increase in metabolism of the previously hypometabolic bilateral cerebelli. The changes observed on the PET CT scan of the brain correlated with clinical improvements. We hypothesize that cellular therapy holds great potential as a treatment modality for autism in combination with standard rehabilitation therapy. Randomized controlled trials are warranted to study their long term effects in treating autism.

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Immune Modulation by Mesenchymal Stem Cells

Cited by 48 publications

References 129 publications

Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

Improvement of Contraction Force in Injured Skeletal Muscle after Autologous Mesenchymal Stroma Cell Transplantation Is Accompanied by Slow to Fast Fiber Type Shift

Clinical Protocols for the Isolation and Expansion of Mesenchymal Stromal Cells

A Case of Autism Showing Clinical Improvements after Cellular Therapy along with PET CT Evidence

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