Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture

Yin, Yuan; Wu, Ruixue; He, Xiao-Tao; Xu, Xinyue; Wang, Jia; Chen, Fa‐Ming

doi:10.1186/s13287-017-0608-0

Cited by 53 publications

(38 citation statements)

References 70 publications

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“…Immune reactions following implantation in vivo is vital to the prognosis of biomaterials in BTE and a new in-vitro assessment approach with inclusion of macrophages has gradually become the main evaluating criterion for the osteogenesis of new fabricated materials [ 2 , 8 ]. Along with advances in the understanding of the divergent effects of distinct subtypes of macrophages (M1 and M2) in tissue regeneration, more and more attention has focused on the strategies for modulating the immune microenvironment around the implants [ 32 ]. The immunomodulatory properties of MSCs on macrophages provides a new means for promoting tissue regeneration and it has been suggested that it be incorporated in design of tissue engineering materials [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, in the present study, the osteogenesis of rBMSCs in the 12.5 μg/mL Lap group was significantly higher than in the other groups. This may be attributed to the following: first, compared with the other groups, flow cytometry implicated less M1 polarization in the 12.5 μg/mL Lap group with a higher expression of anti-inflammatory factors such Arg-1 and IL-10 which are beneficial for osteogenesis [ 32 , 40 ]. Second, the production of proinflammatory factors such as IL-1β, TGF-β, and IL-6 is relatively low in the 12.5 μg/mL Lap group.…”

Section: Discussionmentioning

confidence: 99%

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Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic effects of laponite

Liu

Xiao

et al. 2018

Stem Cell Res Ther

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BackgroundWith the development of osteoimmunology and bone tissue engineering (BTE), it has been recognized that the immunomodulatory properties of bone biomaterials have considerable impact in determining their fate after implantation. In this regard, the polarization of macrophages secondary to biomaterials is postulated to play a crucial role in modulating their osteogenesis; thus, strategies that may facilitate this process engender increasing levels of attention. Whereas a variety of reports highlight the immunomodulation of bone marrow mesenchymal stem cells (BMSCs) in cell therapy or their osteogenesis in BTE, few have focused on the effect of BMSCs in promoting osteogenesis in BTE through regulating the phenotype of macrophages. Accordingly, there is an urgent need to clarify the immunomodulatory properties of agents such as laponite (Lap), which is comprised of bioactive silicate nanoplatelets with excellent osteogenesis-inducing potential, to enhance their use in BTE.MethodsIn the present study, we analyzed the osteoimmunomodulatory properties of Lap alone, as well as following the introduction of BMSCs into Lap, to determine whether BMSCs could modulate its immunomodulatory properties and promote osteogenesis.ResultsIt was found that the BMSCs reversed the polarization of murine-derived macrophage RAW 264.7 cells from M1 as induced by pure Lap to M2 and promoted osteogenesis. In vivo study confirmed that BMSCs combined with Lap initiated a less severe immune response and had an improved effect on bone regeneration compared with Lap alone, which corresponded with the in vitro evaluation.ConclusionThese results suggest that BMSCs could ameliorate the inflammation induced by Lap and enhance its bone formation. The immunomodulatory characteristics of BMSCs suggest that these might be tailored as a new strategy to promote the osteogenic capacity of biomaterials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic effects of laponite

Liu

Xiao

et al. 2018

Stem Cell Res Ther

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“…It should be noted that stimulating factors were completely removed before the supernatants of polarized Mφs were collected for CM production . In addition, the application of CM in investigations can prevent changes in Mφ polarization when directly co‐cultured with BMMSCs, as there is evidence that MSCs exert significant effects on macrophages during in vitro culture . Given that cell sheets generated by stem cell cultures are widely used as cellular materials in regenerative design, we also investigated the influence of various Mφs on matrix production and stem cell sheet formation.…”

Section: Introductionmentioning

confidence: 99%

The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells

Yin

et al. 2017

J Cellular Molecular Medi

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Macrophages (Mφs) are involved in a variety of physiological and pathological events including wound healing and tissue regeneration, in which they play both positive and negative roles depending on their polarization state. In this study, we investigated the cellular behaviours of bone marrow mesenchymal stem cells (BMMSCs) after incubation in different conditioned media (CMs) generated by unpolarized Mφs (M0) or polarized Mφs (M1 and M2). Mφ polarization was induced by stimulation with various cytokines, and CMs were obtained from in vitro Mφ cultures termed CM0, CM1 and CM2 based on each Mφ phenotype. We found that CM1 supported the proliferation and adipogenic differentiation of BMMSCs, whereas CM0 had a remarkable effect on cell osteogenic differentiation. To a certain degree, CM2 also facilitated BMMSC osteogenesis; in particular, cells incubated with CM2 exhibited an enhanced capacity to form robust stem cell sheets. Although incubation with CM1 also increased production of extracellular matrix components, such as fibronectin, COL-1 and integrin b1during sheet induction, the sheets generated by CM2-incubated cells were thicker than those generated by CM1-incubated cells (P < 0.001). Our data suggest that each Mφ phenotype has a unique effect on BMMSCs. Fine-tuning Mφ polarization following transplantation may serve as an effective method to modulate the therapeutic potential of BMMSCs.

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“…Previous studies have shown that the immunosuppressive potential of MSCs derived from bone marrow, adipose, and other sources is negatively in uenced by aging (14,15). In our previous studies, we showed that PDLSCs not only have the ability to reconstruct the periodontal tissue and bone defects (16,17), but also have low immunogenicity and strong immune regulation ability (18).…”

Section: Introductionmentioning

confidence: 91%

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Zhang

Wang

et al. 2020

Preprint

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Abstract Background: Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. Methods: In this study, we compared PDLSCs isolated from young and adult individuals. PDLSCs proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSCs osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining and related quantitative analysis. PDLSCs immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Results: Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of CCND3 and RC3H2, and a downregulation of Runx2, ALP, COL1A1, PPARγ2, CXCL12, FKBP1A, FKBP1B, NCSTN, P2RX7, PPP3CB, RIPK2, SLC11A1, and TP53 in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, COL1A1, and PPARγ2 in the adult group was decreased, whereas that of CCND3 increased. Conclusions: Taken together, aging influences biological and immunological characteristics of PDLSCs, and thus it is more appropriate to utilized PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.

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Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture

Cited by 53 publications

References 70 publications

Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic effects of laponite

Impact of bone marrow mesenchymal stem cell immunomodulation on the osteogenic effects of laponite

The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

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