Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells

Ravanidis, Stylianos; Bogie, Jeroen F. J.; Donders, Raf; Deans, Robert; Hendriks, Jerome J. A.; Stinissen, Piet; Pinxteren, Jef; Mays, Robert W.; Hellings, Niels

doi:10.1155/2017/2353240

Cited by 5 publications

(4 citation statements)

References 71 publications

(111 reference statements)

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“…In line with these studies, we previously demonstrated that muramyl dipeptide (MDP), a constituent of the bacterial cell wall, plays a crucial role in promoting the immunomodulatory mechanism of hUCB-MSCs, and preconditioning with MDP significantly augmented the therapeutic efficacy of hUCB-MSCs against experimental colitis 25. The crosstalk between the risk factors of a particular disease, including dysregulated activation of immune cells, and MSCs can be employed to identify its mode of action and develop disease-specific stem cell therapy 26. In the present study, we have suggested priming with MC granules as a possible approach to enhancing stem cell-based therapy aimed at reducing skin inflammation and tissue degeneration in AD.…”

Section: Discussionmentioning

confidence: 99%

Disease-specific primed human adult stem cells effectively ameliorate experimental atopic dermatitis in mice

Lee¹,

Kim²,

Lee³

et al. 2019

Theranostics

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Although human mesenchymal stem cells (hMSCs) hold considerable promise as an alternative therapeutic reagent for allergic disorders including atopic dermatitis (AD), the strategy for enhancing hMSC-based therapy remains challenging. We sought to investigate whether preconditioning with mast cell (MC) granules could enhance the therapeutic efficiency of human umbilical cord blood-derived MSCs (hUCB-MSCs) against AD. Methods: AD was experimentally induced in NC/Nga mice by repeated applications of 4% sodium dodecyl sulfate (SDS) and dermatophagoides farinae (Df) extract, and preconditioned hUCB-MSCs were subcutaneously injected. The therapeutic effect was determined by gross examination and additional ex vivo experiments performed using blood and skin samples to determine the resolution of allergic inflammation. To explore the underlying mechanisms, several co-culture assays with primary isolated immune cells and wound closure assays were conducted. Results: Pretreatment of MC granules enhanced the therapeutic effects of hUCB-MSCs by attenuating the symptoms of AD in an experimental animal model. MC granule-primed cells suppressed the activation of major disease-inducing cells, MCs and B lymphocytes more efficiently than naïve cells both in vitro and in vivo . Histamine-mediated upregulation of the COX-2 signaling pathway was shown to play a crucial role in suppression of the allergic immune response by MC-pretreated hUCB-MSCs. Moreover, MC pretreatment improved the wound healing ability of hUCB-MSCs. Conclusions: Our findings indicate that pre-exposure to MC granules improved the therapeutic effect of hUCB-MSCs on experimental AD by resolving the allergic immune reaction and accelerating the tissue regeneration process more efficiently than naïve cells, suggesting a potential enhancement strategy for stem cell-based therapy.

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Section: Discussionmentioning

confidence: 99%

Disease-specific primed human adult stem cells effectively ameliorate experimental atopic dermatitis in mice

Lee¹,

Kim²,

Lee³

et al. 2019

Theranostics

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“…Researchers demonstrated that MSCs skew monocytes towards an anti-inflammatory phenotype, thereby facilitating Treg differentiation 78 . MAPC cells have also been demonstrated to induce a comparable anti-inflammatory phenotype on myeloid cells in vitro 55 and in vivo 18 , however, the effect of MAPC cells on CD14 + monocytes responsible for their involvement in MAPC-mediated induction of Tregs remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms

Valentin-Torres

Day

Taggart

et al. 2021

Sci Rep

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Dysregulation of the immune system can initiate chronic inflammatory responses that exacerbate disease pathology. Multipotent adult progenitor cells (MAPC cells), an adult adherent bone-marrow derived stromal cell, have been observed to promote the resolution of uncontrolled inflammatory responses in a variety of clinical conditions including acute ischemic stroke, acute myocardial infarction (AMI), graft vs host disease (GvHD), and acute respiratory distress syndrome (ARDS). One of the proposed mechanisms by which MAPC cells modulate immune responses is via the induction of regulatory T cells (Tregs), however, the mechanism(s) involved remains to be fully elucidated. Herein, we demonstrate that, in an in vitro setting, MAPC cells increase Treg frequencies by promoting Treg proliferation and CD4+ T cell differentiation into Tregs. Moreover, MAPC cell-induced Tregs (miTregs) have a more suppressive phenotype characterized by increased expression of CTLA-4, HLA-DR, and PD-L1 and T cell suppression capacity. MAPC cells also promoted Treg activation by inducing CD45RA+ CD45RO+ transitional Tregs. Additionally, we identify transforming growth factor beta (TGFβ) as an essential factor for Treg induction secreted by MAPC cells. Furthermore, inhibition of indoleamine 2, 3-dioxygenase (IDO) resulted in decreased Treg induction by MAPC cells demonstrating IDO involvement. Our studies also show that CD14+ monocytes play a critical role in Treg induction by MAPC cells. Our study describes MAPC cell dependent Treg phenotypic changes and provides evidence of potential mechanisms by which MAPC cells promote Treg differentiation.

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“…Extensive research has shown that the behavior of MSCs has immunoregulatory potential following activation by macrophages [76,77] efficaciously deliver CCL2 secreted by human MSCs, which acts a part in not only recruiting macrophages but also driving their transformation to an M2 neuroprotective phenotype, to preserve motor neurons and myelin in the lesion [92].…”

Section: Communication Between Macrophages and Mscsmentioning

confidence: 99%

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

Wang

yang

2020

Preprint

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The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord [1]. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord [2]. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs. Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry and function must be overcame[3]. Notably, the pro -inflammatory and anti-inflammatory effect s of cell-cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit[4]. Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSCs transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering [5]. MSCs transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influences implant integration by improving the healing process[6]. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses. Here, we review the advances in combinatorial biomaterial scaffolds and MSCs transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSCs transplantation and its future direction for neuronal regeneration will be presented.

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Crosstalk with Inflammatory Macrophages Shapes the Regulatory Properties of Multipotent Adult Progenitor Cells

Cited by 5 publications

References 71 publications

Disease-specific primed human adult stem cells effectively ameliorate experimental atopic dermatitis in mice

Disease-specific primed human adult stem cells effectively ameliorate experimental atopic dermatitis in mice

Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms

Biomaterial-supported MSCs transplantation enhances cell-cell communication for spinal cord injury

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