Exploring the roles of MSCs in infections: focus on bacterial diseases

Marrazzo, Pasquale; Crupi, Annunziata; Alviano, Francesco; Teodori, Laura; Bonsi, Laura

doi:10.1007/s00109-019-01752-6

Cited by 51 publications

(54 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Methicillin‐resistant Staphylococcus aureus (MRSA) in particular accounts for high mortality worldwide and is responsible for many chronic implant infections . The use of mesenchymal stem cell (MSC) to treat bacterial infections has received increasing attention in recent years, based on in vitro studies documenting direct bactericidal activity . Thus, it is possible that administration of MSC may be a means of potentiating conventional antibiotic therapy, it is therefore important to elucidate more fully the mechanisms underlying MSC antimicrobial activity, both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Chow

Johnson

Impastato

et al. 2019

Stem Cells Translational Medicine

108

View full text Add to dashboard Cite

Mesenchymal stem cells (MSC) have been shown to improve wound healing and sup-press inflammatory immune responses. Newer research also indicates that MSC exhibit antimicrobial activity, although the mechanisms underlying this activity have not been fully elucidated. Therefore, we conducted in vitro and in vivo studies to examine the ability of resting and activated MSC to kill bacteria, including multidrug resistant strains. We investigated direct bacterial killing mechanisms and the interaction of MSC with host innate immune responses to infection. In addition, the activity of MSC against chronic bacterial infections was investigated in a mouse biofilm infection model. We found that MSC exhibited high levels of spontaneous direct bactericidal activity in vitro. Moreover, soluble factors secreted by MSC inhibited Staphylococcus aureus biofilm formation in vitro and disrupted the growth of established biofilms. Secreted factors from MSC also elicited synergistic killing of drug-resistant bacteria when combined with several major classes of antibiotics. Other studies demonstrated interactions of activated MSC with host innate immune responses, including triggering of neutrophil extracellular trap formation and increased phagocytosis of bacteria. Finally, activated MSC administered systemically to mice with established S. aureus biofilm infections significantly reduced bacterial numbers at the wound site and improved wound healing when combined with antibiotic therapy. These results indicate that MSC generate multiple direct and indirect, immunologically mediated antimicrobial activities that combine to help eliminate chronic bacterial infections when the cells are administered therapeutically.

show abstract

Section: Introductionmentioning

confidence: 99%

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Chow

Johnson

Impastato

et al. 2019

Stem Cells Translational Medicine

108

View full text Add to dashboard Cite

show abstract

“…Moreover, MSCs exhibit antimicrobial activity through the secretion of antimicrobial peptides (AMPs), such as cathelicidin peptide LL-37, hepcidin, β-defensin 2, lipocalin 2, and Hepcidin [71,72].These AMPs act in destroying bacterias by either altering the integrity of the microbial membrane or by encouraging the release of proinflammatory cytokines which in turn favors the recruitment of immune cells [71]. Therefore, there is an over-stimulation of the immune cells, as the formation of neutrophil extracellular traps (NETs) by neutrophils [71].…”

Section: Paracrine Activitymentioning

confidence: 99%

“…Thus, MSCs can support the host by immunosuppressing the environment by: (i) refrying the intensification of pathological symptoms; (ii) helping to cure damaged tissue or organ; and (iii) allowing the formation of an immune tolerant environment. However, excessive immune suppression can cause the completely different effect, impeding the host from attacking the infection, and instead, favoring microbial effectors to spread [72].…”

Section: Paracrine Activitymentioning

confidence: 99%

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

Jimenez-Puerta

Marchal

López‐Ruiz

et al. 2020

JCM

View full text Add to dashboard Cite

Due to the great therapeutic interest that involves the translation of mesenchymal stromal cells (MSCs) into clinical practice, they have been widely studied as innovative drugs, in order to treat multiple pathologies. MSC-based cell therapy involves the administration of MSCs either locally or systemically into the receptor body where they can traffic and migrate towards the affected tissue and participate in the process of healing. The therapeutic effects of MSCs compromise of different mechanisms such as the functional integration of differentiated MSCs into diseased host tissue after transplantation, their paracrine support, and their impact on the regulation of both the innate and the acquired immune system. Here, we establish and provide recent advances about the principal mechanisms of action through which MSCs can perform their activity and effect as a therapeutic tool. The purpose of this review is to examine and discuss the MSCs capacity of migration, their paracrine effect, as well as MSC-mediated modifications on immune cell responses.

show abstract

“…A wide range of experimental and clinical studies have underlined the immunomodulatory, anti‐inflammatory, and wound healing capabilities of mesenchymal stem cells (MSCs), leading to their application in a range of reparative and regenerative approaches. However, these multifunctional cells also possess another less appreciated ability, with multiple in vitro studies providing evidence for the potent and direct bactericidal activity of MSCs . Given the unfortunate rise of antibiotic‐resistant bacteria and the devastating effects observed following infections in debilitated patients, many have sought to explore cotreatment with MSCs as a means to potentiate conventional antibiotic therapy .…”

mentioning

confidence: 99%

“…However, these multifunctional cells also possess another less appreciated ability, with multiple in vitro studies providing evidence for the potent and direct bactericidal activity of MSCs . Given the unfortunate rise of antibiotic‐resistant bacteria and the devastating effects observed following infections in debilitated patients, many have sought to explore cotreatment with MSCs as a means to potentiate conventional antibiotic therapy . Previous research efforts have demonstrated that MSCs directly influence the immunological properties of macrophages and neutrophils via secreted factors, while they also produce antimicrobial peptides that directly kill bacteria either by disrupting the integrity of the microbial membrane or by recruiting immune cells following the induced release of proinflammatory cytokines.…”

mentioning

confidence: 99%

A preview of selected articles

Atkinson

2020

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Exploring the roles of MSCs in infections: focus on bacterial diseases

Cited by 51 publications

References 120 publications

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

A preview of selected articles

Contact Info

Product

Resources

About