Correction to: Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies

Noronha, Nádia de Cássia; Mizukami, Amanda; Caliári-Oliveira, Carolina; Cominal, Juçara Gastaldi; Rocha, José Lucas Martins; Covas, Dimas Tadeu; Swiech, Kamilla; Malmegrim, Kelen Cristina Ribeiro

doi:10.1186/s13287-019-1259-0

Cited by 41 publications

(50 citation statements)

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“…Studies have shown that IFN-γ is a key player in activating the immunomodulatory function of murine and human MSCs through the production of several factors, including HGF and IL-10, which is consistent with the results of our study [85,86]. More importantly, through in ammation enriched with pro-in ammatory cytokines such as IFN-γ, MSCs could be activated or primed, and the upregulation of major histocompatibility complex class I (MHC-I) can lead to improved survival [37].…”

Section: Discussionsupporting

confidence: 91%

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3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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Background: Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration.Methods: 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL+MSC (NGC multi-functionalized with 106 canine AdMSC embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokines IL-6 and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve.Results: The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL+MSC group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair.Conclusions: 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach, support the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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Section: Discussionsupporting

confidence: 91%

“…Paracrine and regenerative effects depend on AdMSC engraftment [31,37,73] In our study, AdMSCs embedded in HFB survived for 30 days after transplantation into the NGC and were co-localized with BDNF and GDNF. Similarly, human AdMSCs transplanted after root avulsion in rats increased neuronal survival mediated by BDNF, GDNF, and HGF.…”

Section: Discussionmentioning

confidence: 58%

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Rodríguez-Sánchez

Pinto

Cartarozzi

et al. 2020

Preprint

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“…The safety of this MSC-based therapy has also been demonstrated in early-stage clinical studies, although in relatively small patient cohorts with different MSC sources and study designs [87,111,112,114]. To date there are no established priming/preconditioning protocols designed to improve the therapeutic effect of MSCs to target viral infections [115,116]. Some approaches have been reported only to boost the antimicrobial properties of MSCs [113].…”

Section: Future Directions Of Msc-based Therapies For Covid-19 and Otmentioning

confidence: 99%

“…Notably, hypoxia priming of MSCs induces autophagy [117], increases microvesicles and growth factors release [118,119], upregulates chemokine-receptors expression, decreases cellular senescence and apoptosis, and promotes higher retention in vivo and greater therapeutic efficacy [120]. Therefore, new strategies to improve antiviral MSC properties should be developed for production of more robust MSC-based products to treat patients with viral infection diseases, including COVID-19 [116,121,122].…”

Section: Future Directions Of Msc-based Therapies For Covid-19 and Otmentioning

confidence: 99%

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Rocha

Oliveira

Noronha

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.

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“…Under certain pathological conditions, ischemic or inflammatory environments might be detrimental to the survival of MSCs. Researchers have used some proinflammatory cytokine pretreatments, such as IFN-γ, TNF-α, and IL-17, among others, to promote MSC expression of IDO and NO, which increases their immunosuppressive abilities (18,(134)(135)(136)(137)(138).…”

Section: Strategy 3: Rebuilding Autoimmune Tolerance Using Various Immentioning

confidence: 99%

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

et al. 2020

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Conditions in which abnormal or excessive immune responses exist, such as autoimmune diseases (ADs), graft-versus-host disease, transplant rejection, and hypersensitivity reactions, are serious hazards to human health and well-being. The traditional immunosuppressive drugs used to treat these conditions can lead to decreased immune function, a higher risk of infection, and increased tumor susceptibility. As an alternative therapeutic approach, cell therapy, in which generally intact and living cells are injected, grafted, or implanted into a patient, has the potential to overcome the limitations of traditional drug treatment and to alleviate the symptoms of many refractory diseases. Cell therapy could be a powerful approach to induce immune tolerance and restore immune homeostasis with a deeper understanding of immune tolerance mechanisms and the development of new techniques. The purpose of this review is to describe the current panoramic scope of cell therapy for immune-mediated disorders, discuss the advantages and disadvantages of different types of cell therapy, and explore novel directions and future prospects for these tolerogenic therapies.

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Correction to: Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies

Cited by 41 publications

References 1 publication

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

3D-printed Nerve Guidance Conduits Multi-functionalized with Canine Multipotent Mesenchymal Stromal Cells Promote Neuroregeneration after Sciatic Nerve Injury in Rats

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

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