Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis

Seebach, Elisabeth; Holschbach, J.; Buchta, Nicole; Bitsch, Rudi G.; Kleinschmidt, Kerstin; Richter, Wiltrud

doi:10.1016/j.actbio.2015.03.019

Cited by 37 publications

(24 citation statements)

References 59 publications

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“…Masquelet or induced-membrane technique) could for example be considered. In case of a Masquelet procedure, the surgeon should be sure that there is no remaining infection, as a recent experimental study by Seebach et al showed this can be worsened by the introduction of mesenchymal stromal stem cells [129]. Of course, definitive treatment with external fixation (i.e.…”

Section: Non-union Lacking Clinical Signs Of Infectionmentioning

confidence: 99%

Infection after fracture fixation: Current surgical and microbiological concepts

Metsemakers

Kuehl

Moriarty

et al. 2018

Injury

409

368

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One of the most challenging complications in trauma surgery is infection after fracture fixation (IAFF). IAFF may result in permanent functional loss or even amputation of the affected limb in patients who may otherwise be expected to achieve complete, uneventful healing. Over the past decades, the problem of implant related bone infections has garnered increasing attention both in the clinical as well as preclinical arenas; however this has primarily been focused upon prosthetic joint infection (PJI), rather than on IAFF. Although IAFF shares many similarities with PJI, there are numerous critical differences in many facets including prevention, diagnosis and treatment. Admittedly, extrapolating data from PJI research to IAFF has been of value to the trauma surgeon, but we should also be aware of the unique challenges posed by IAFF that may not be accounted for in the PJI literature. This review summarizes the clinical approaches towards the diagnosis and treatment of IAFF with an emphasis on the unique aspects of fracture care that distinguish IAFF from PJI. Finally, recent developments in anti-infective technologies that may be particularly suitable or applicable for trauma patients in the future will be briefly discussed.

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Section: Non-union Lacking Clinical Signs Of Infectionmentioning

confidence: 99%

Infection after fracture fixation: Current surgical and microbiological concepts

Metsemakers

Kuehl

Moriarty

et al. 2018

Injury

409

368

View full text Add to dashboard Cite

show abstract

“…Aside from their ECM-modifying properties, the immunomodulatory properties of MSCs are intriguing from a therapeutic standpoint but must be used carefully, because MSC treatment, concurrent with a Staphylococcus aureus infection, was shown to increase the severity of bone loss, despite increased MSC proinflammatory cytokine expression, in an osteomyelitis model [140]. Conversely, encouraging results were recently published from a small idiopathic osteonecrosis trial in Japan, where BM-MSCs were isolated, cultured for 2 weeks, and returned to osteonecrotic patients along with tricalcium phosphate chips (Osferion) and tricortical iliac crest bone [141]; after a 12-week rehabilitation program, all patients reported reduced pain and increased physical function with no serious adverse events reported in the study [142].…”

Section: Muscles and Miscellanymentioning

confidence: 99%

Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies

2016

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Adult mesenchymal stem cells (MSCs) represent a subject of intense experimental and biomedical interest. Recently, trophic activities of MSCs have become the topic of a number of revealing studies that span both basic and clinical fields. In this review, we focus on recent investigations that have elucidated trophic mechanisms and shed light on MSC clinical efficacy relevant to musculoskeletal applications. Innate differences due to MSC sourcing may play a role in the clinical utility of isolated MSCs. Pain management, osteochondral, nerve, or blood vessel support by MSCs derived from both autologous and allogeneic sources have been examined. Recent mechanistic insights into the trophic activities of these cells point to ultimate regulation by nitric oxide, nuclear factor-kB, and indoleamine, among other signaling pathways. Classic growth factors and cytokines—such as VEGF, CNTF, GDNF, TGF-β, interleukins (IL-1β, IL-6, and IL-8), and C-C ligands (CCL-2, CCL-5, and CCL-23)—serve as paracrine control molecules secreted or packaged into extracellular vesicles, or exosomes, by MSCs. Recent studies have also implicated signaling by microRNAs contained in MSC-derived exosomes. The response of target cells is further regulated by their microenvironment, involving the extracellular matrix, which may be modified by MSC-produced matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs. Trophic activities of MSCs, either resident or introduced exogenously, are thus intricately controlled, and may be further fine-tuned via implant material modifications. MSCs are actively being investigated for the repair and regeneration of both osteochondral and other musculoskeletal tissues, such as tendon/ligament and meniscus. Future rational and effective MSC-based musculoskeletal therapies will benefit from better mechanistic understanding of MSC trophic activities, for example using analytical “-omics” profiling approaches.

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“…These include the use of growth factors, such as bone morphogenic proteins, or application of pre‐differentiated mesenchymal stem cells (MSCs), stromal cells which have the ability to differentiate into osteoblasts and chondrocytes . However, these treatments require further experimentation, as data on the efficacy of utilizing MSCs are mixed, with one study reporting a detrimental effect on osteomyelitis following implantation in a rat model …”

Section: Current Burden and Treatment Of Extremity Traumamentioning

confidence: 99%

Inhibition of fracture healing in the presence of contamination byStaphylococcus aureus: Effects of growth state and immune response

et al. 2017

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Extremity injuries comprise a significant portion of trauma, affecting quality of life, financial burden, and return to duty. Bacterial contamination is commonly associated with failure to heal, despite antibiotic treatment, suggesting that additional therapies must be developed to combat these complications. Treatment failure is likely due to the presence of resistant microbial communities known as biofilms. Biofilm bacteria are able to elicit a direct inhibition of healing through a multitude of known factors. However, they likely also inhibit healing through alteration of the inflammatory response. As inflammation is a critical step in fracture healing, how the presence of biofilm bacteria shifts this response to one that is suboptimal for healing is an important consideration that is currently understudied. The profile of inflammatory factors in response to biofilm bacteria is unique and distinct from those induced during normal healing or by planktonic bacteria alone. This review will examine the presence of inflammatory factors during normal healing and those induced by contaminating bacteria, and will discuss how these differences may ultimately lead to nonunion. Specifically, this review will focus on the Th1/Th2/Th17 type inflammatory responses and how shifts in the balance of these responses during infection can lead to both ineffective clearance and disruption of fracture healing. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1845-1854, 2017.

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Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis

Cited by 37 publications

References 59 publications

Infection after fracture fixation: Current surgical and microbiological concepts

Infection after fracture fixation: Current surgical and microbiological concepts

Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies

Inhibition of fracture healing in the presence of contamination byStaphylococcus aureus: Effects of growth state and immune response

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