Iron nanoparticle-labeled murine mesenchymal stromal cells in an osteoarthritic model persists and suggests anti-inflammatory mechanism of action

Hamilton, Amanda M.; Cheung, Wing-Yee; Gómez‐Aristizábal, Alejandro; Sharma, Anjali; Nakamura, Sayaka; Chaboureau, A.; Bhatt, S.; Rabani, R.; Kapoor, Mohit; Foster, Paula J.; Viswanathan, Sowmya

doi:10.1371/journal.pone.0214107

Cited by 24 publications

(23 citation statements)

References 38 publications

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“…Hamilton et al demonstrated a decrease in proportion of iNOS and reduction of pro-inflammatory macrophages after MSCs injection in a murine OA model (78). It was reported that MSCs decreased synovial inflammation and fibrosis (78).…”

Section: Macrophages and Mesenchymal Stem Cellsmentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

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Section: Macrophages and Mesenchymal Stem Cellsmentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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“…Finally, M2 macrophages promote the repair of damaged tissues. In the mouse OA model, Hamilton et al show that MSC treatment (intra-articular injection) down-regulates the level of iNOS in macrophages, and finally decreases the formation of M1 macrophages [ 51 ]. Collectively, the above findings suggest that MSCs suppress inflammation by converting macrophages into the M2 phenotype, which would make them a promising therapeutic reagent for OA.…”

Section: Macrophages Are An Emerging Target For Oa Treatmentmentioning

confidence: 99%

“… [ 16 ] Rapamycin Primary human monocytes Patients with osteoarthritis mTOR Enhance the function of M1 macrophages and inhibit the activity of M2 macrophages Preclinical stage/NA DXMS promotes the conversion of macrophages into M2 macrophages to relieve OA symptoms. [ 16 , 47 ] Biological molecules Cell Mesenchymal stem cell (MSC) Synovial macrophages of OA patients In vitro co-culture OA model consisting of patient-matched cartilage and macrophages NA Inhibit the activity of M1 macrophages and induce polarization of M2 macrophages Preclinical stage/NA MSCs promote the formation of M2 macrophages, thereby relieving OA symptoms [ 46 , 51 ] TissueGene-C Human joint macrophages Patients with osteoarthritis NA Promote the formation of M2 macrophages Phase III of a clinical trial/NA TissueGene-C induces the formation of M2 macrophages, thereby relieving pain in patients with OA. [ 52 , 53 ] Protein R-spondin-2 NA NA Wnt/β-catenin NA Preclinical stage/NA The formatio...…”

Section: Table A1mentioning

confidence: 99%

An Emerging Target in the Battle against Osteoarthritis: Macrophage Polarization

Sun

Zuo

Kuang

2020

IJMS

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Osteoarthritis (OA) is one of the most prevalent chronic joint diseases worldwide, which causes a series of problems, such as joint pain, muscle atrophy, and joint deformities. Benefiting from some advances in the clinical treatment of OA, the quality of life of OA patients has been improved. However, the clinical need for more effective treatments for OA is still very urgent. Increasing findings show that macrophages are a critical breakthrough in OA therapy. Stimulated by different factors, macrophages are differentiated into two phenotypes: the pro-inflammatory M1 type and anti-inflammatory M2 type. In this study, various therapeutic reagents for macrophage-dependent OA treatment are summarized, including physical stimuli, chemical compounds, and biological molecules. Subsequently, the mechanisms of action of various approaches to modulating macrophages are discussed, and the signaling pathways underlying these treatments are interpreted. The NF-κB signaling pathway plays a vital role in the occurrence and development of macrophage-mediated OA, as NF-κB signaling pathway agonists promote the occurrence of OA, whereas NF-κB inhibitors ameliorate OA. Besides, several signaling pathways are also involved in the process of OA, including the JNK, Akt, MAPK, STAT6, Wnt/β-catenin, and mTOR pathways. In summary, macrophage polarization is a critical node in regulating the inflammatory response of OA. Reagents targeting the polarization of macrophages can effectively inhibit inflammation in the joints, which finally relieves OA symptoms. Our work lays the foundation for the development of macrophage-targeted therapeutic molecules and helps to elucidate the role of macrophages in OA.

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“…MSCs have been widely studied as a therapeutic tool for OA due to their chondrogenic potential and immunomodulatory capacities [ 117 ]. MSCs can not only suppress the activation of M1 macrophages and reprogram them to polarize into M2 macrophages, but can also ameliorate synovial inflammation in a mouse OA model [ 117 , 118 ]. However, M1 macrophages have been shown to impede the chondrogenic differentiation of MSCs, indicating that although MSCs can improve the inflammatory environment and induce M2 polarization, exacerbated inflammation can in turn inhibit their functions [ 41 ].…”

Section: Application Of Immunomodulatory Biomaterials In Musculoskeletal Soft Tissue Regenerationmentioning

confidence: 99%

Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization

Xie

Wang

et al. 2021

Bioactive Materials

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Musculoskeletal disorders are common in clinical practice. Repairing critical-sized defects in musculoskeletal systems remains a challenge for researchers and surgeons, requiring the application of tissue engineering biomaterials. Successful application depends on the response of the host tissue to the biomaterial and specific healing process of each anatomical structure. The commonly-held view is that biomaterials should be biocompatible to minimize local host immune response. However, a growing number of studies have shown that active modulation of the immune cells, particularly macrophages, via biomaterials is an effective way to control immune response and promote tissue regeneration as well as biomaterial integration. Therefore, we critically review the role of macrophages in the repair of injured musculoskeletal system soft tissues, which have relatively poor regenerative capacities, as well as discuss further enhancement of target tissue regeneration via modulation of macrophage polarization by biomaterial-mediated immunomodulation (biomaterial properties and delivery systems). This active regulation approach rather than passive-evade strategy maximizes the potential of biomaterials to promote musculoskeletal system soft tissue regeneration and provides alternative therapeutic options for repairing critical-sized defects.

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Iron nanoparticle-labeled murine mesenchymal stromal cells in an osteoarthritic model persists and suggests anti-inflammatory mechanism of action

Cited by 24 publications

References 38 publications

Macrophage: A Potential Target on Cartilage Regeneration

Macrophage: A Potential Target on Cartilage Regeneration

An Emerging Target in the Battle against Osteoarthritis: Macrophage Polarization

Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization

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