Preclinical and Clinical Amelioration of Bone Fractures with Mesenchymal Stromal Cells: a Systematic Review and Meta-Analysis

Yi, Hanxiao; Wang, Yang; Liang, Qunying; Mao, Xia

doi:10.1177/09636897211051743

Cited by 6 publications

(2 citation statements)

References 58 publications

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“…However, no studies with patients have assessed the effect of these growth factors on fracture-healing speed. The available clinical studies on the amelioration of fracturehealing by MSCs in patients (not specifically focusing on healing acceleration) were summarized in a systematic review and metaanalysis by Yi et al (95), which revealed no decrease in healing time in the MSC group. The included studies with human patients differed largely in their patient collectives and modes of MSC application (96)(97)(98)(99).…”

Section: Growth Factorsmentioning

confidence: 99%

Methods to accelerate fracture healing – a narrative review from a clinical perspective

Ganse

2024

Front. Immunol.

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Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors. Fracture healing usually takes several weeks to months, during which patients are frequently immobilized and unable to work. As immobilization is associated with negative health and socioeconomic effects, it would be desirable if fracture healing could be accelerated and the healing time shortened. However, interventions for this purpose are not yet part of current clinical treatment guidelines, and there has never been a comprehensive review specifically on this topic. Therefore, this narrative review provides an overview of the available clinical evidence on methods that accelerate fracture healing, with a focus on clinical applicability in healthy patients without bone disease. The most promising methods identified are the application of axial micromovement, electromagnetic stimulation with electromagnetic fields and direct electric currents, as well as the administration of growth factors and parathyroid hormone. Some interventions have been shown to reduce the healing time by up to 20 to 30%, potentially equivalent to several weeks. As a combination of methods could decrease the healing time even further than one method alone, especially if their mechanisms of action differ, clinical studies in human patients are needed to assess the individual and combined effects on healing progress. Studies are also necessary to determine the ideal settings for the interventions, i.e., optimal frequencies, intensities, and exposure times throughout the separate healing phases. More clinical research is also desirable to create an evidence base for clinical guidelines. To make it easier to conduct these investigations, the development of new methods that allow better quantification of fracture-healing progress and speed in human patients is needed.

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Section: Growth Factorsmentioning

confidence: 99%

Methods to accelerate fracture healing – a narrative review from a clinical perspective

Ganse

2024

Front. Immunol.

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“…Similarly, the study of Yi et al showed encouraging results from the use of MSCs in fractures, both in animal and human studies. Although the study assesses the administration of stem cells alone, their application seems to be effective in the treatment of bone fractures [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Bone Regeneration with Mesenchymal Stem Cells in Scaffolds: Systematic Review of Human Clinical Trials

Theodosaki,

Tzemi,

Galanis

et al. 2024

Stem Cell Rev and Rep

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The aim of the study is to determine the effectiveness of stem cells in scaffolds in the treatment of bone deficits, in regard of bone regeneration, safety, rehabilitation and quality of life in humans. The systematic review was conducted in accordance with PRISMA 2020. A systematic search was conducted in three search engines and two registries lastly in 29-9-2022.for studies of the last 15 years. The risk of bias was assessed with RoB-2, ROBINS- I and NIH Quality of Before-After (Pre-Post) Studies with no Control group. The certainty of the results was assessed with the GRADE assessment tool. Due to heterogeneity, the results were reported in tables, graphs and narratively. The study protocol was published in PROSPERO with registration number CRD42022359049. Of the 10,091 studies retrieved, 14 were meeting the inclusion criteria, and were qualitatively analyzed. 138 patients were treated with mesenchymal stem cells in scaffolds, showing bone healing in all cases, and even with better results than the standard care. The adverse events were mild in most cases and in accordance with the surgery received. When assessed, there was a rehabilitation of the deficit and a gain in quality of life was detected. Although the heterogeneity between the studies and the small number of patients, the administration of mesenchymal stem cells in scaffolds seems safe and effective in the regeneration of bone defects. These results pave the way for the conduction of more clinical trials, with greater number of participants, with more standardized procedures. Graphical Abstract

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Immunomodulation Using BMP‐7 and IL‐10 to Enhance the Mineralization Capacity of Bone Progenitor Cells in a Fracture Hematoma‐Like Environment

Wiesli,

Huber,

Weisse

et al. 2024

Adv Healthcare Materials

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Following biomaterial implantation, a failure to resolve inflammation during the formation of a fracture hematoma can significantly limit the biomaterial's ability to facilitate bone regeneration. This study aimed to combine the immunomodulatory and osteogenic effects of BMP‐7 and IL‐10 with the regenerative capacity of collagen‐hydroxyapatite (CHA) scaffolds to enhance in vitro mineralization in a hematoma‐like environment. Incubation of CHA scaffolds with human whole blood led to rapid adsorption of fibrinogen, significant stiffening of the scaffold, and the formation of a hematoma‐like environment characterized by a limited capacity to support the infiltration of human bone progenitor cells, a significant upregulation of inflammatory cytokines and acute phase proteins, and significantly reduced osteoconductivity. CHA scaffolds functionalized with BMP‐7 and IL‐10 significantly downregulated the production of key inflammatory cytokines, including IL‐6, IL‐8, and leptin, creating a more permissive environment for mineralization, ultimately enhancing the biomaterial's osteoconductivity. In conclusion, targeting the onset of inflammation in the early phase of bone healing using BMP‐7 and IL‐10 functionalized CHA scaffolds is a promising approach to effectively downregulate inflammatory processes while fostering a more permissive environment for bone regeneration.This article is protected by copyright. All rights reserved

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Preclinical and Clinical Amelioration of Bone Fractures with Mesenchymal Stromal Cells: a Systematic Review and Meta-Analysis

Cited by 6 publications

References 58 publications

Methods to accelerate fracture healing – a narrative review from a clinical perspective

Methods to accelerate fracture healing – a narrative review from a clinical perspective

Bone Regeneration with Mesenchymal Stem Cells in Scaffolds: Systematic Review of Human Clinical Trials

Immunomodulation Using BMP‐7 and IL‐10 to Enhance the Mineralization Capacity of Bone Progenitor Cells in a Fracture Hematoma‐Like Environment

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