CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity

Tan, Kezhe; Zhu, Hongtao; Zhang, Jianfang; Ouyang, Weili; Tang, Jianfeng; Zhang, Youming; Qiu, Lugui; Liu, Xueqing; Ding, Zhaoping; Deng, Xiaoming

doi:10.1155/2019/8717694

Cited by 50 publications

(46 citation statements)

References 29 publications

(45 reference statements)

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“…Interestingly, flow cytometry analysis of the 2D cultures revealed an increase in CD73 mean fluorescence intensity, in both inflamed BMMSCs and CPSCs. Tan et al observed that the presence of a subpopulation of MSCs with increased CD73 expression was associated with better cardiac repair, as a result of involvement in the regulation of local immune response through purinergic signaling 49 . In addition, they demonstrated that this high CD73-expressing MSC population was able to recruit CD11b+/CCR2+ macrophages with an anti-inflammatory profile.…”

Section: Discussionmentioning

confidence: 99%

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

Bauza

Pastò

McCulloch

et al. 2020

Sci Rep

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Cartilage repair in osteoarthritic patients remains a challenge. Identifying resident or donor stem/progenitor cell populations is crucial for augmenting the low intrinsic repair potential of hyaline cartilage. Furthermore, mediating the interaction between these cells and the local immunogenic environment is thought to be critical for long term repair and regeneration. In this study we propose articular cartilage progenitor/stem cells (CPSC) as a valid alternative to bone marrow-derived mesenchymal stem cells (BMMSC) for cartilage repair strategies after trauma. Similar to BMMSC, CPSC isolated from osteoarthritic patients express stem cell markers and have chondrogenic, osteogenic, and adipogenic differentiation ability. In an in vitro 2D setting, CPSC show higher expression of SPP1 and LEP, markers of osteogenic and adipogenic differentiation, respectively. CPSC also display a higher commitment toward chondrogenesis as demonstrated by a higher expression of ACAN. BMMSC and CPSC were cultured in vitro using a previously established collagen-chondroitin sulfate 3D scaffold. The scaffold mimics the cartilage niche, allowing both cell populations to maintain their stem cell features and improve their immunosuppressive potential, demonstrated by the inhibition of activated PBMC proliferation in a co-culture setting. As a result, this study suggests articular cartilage derived-CPSC can be used as a novel tool for cellular and acellular regenerative medicine approaches for osteoarthritis (OA). In addition, the benefit of utilizing a biomimetic acellular scaffold as an advanced 3D culture system to more accurately mimic the physiological environment is demonstrated.

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Section: Discussionmentioning

confidence: 99%

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

Bauza

Pastò

McCulloch

et al. 2020

Sci Rep

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“…The heterogeneity in CD73 expression and its catalytic products may have distinct modulatory effects on the local immune response. This statement may explain the differences observed during tissue regenerative cell-based therapy (Tan et al, 2019).…”

Section: Regulation Of Metabolic Pathwaysmentioning

confidence: 81%

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

Najar

Martel‐Pelletier

Pelletier

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stem cell (MSC) therapy represents a promising approach for the treatment of osteoarthritis (OA). MSCs can be readily isolated from multiple sources and expanded ex vivo for possible clinical application. They possess a unique immunological profile and regulatory machinery that underline their therapeutic effects. They also have the capacity to sense the changes within the tissue environment to display the adequate response. Indeed, there is a close interaction between MSCs and the host cells. Accordingly, MSCs demonstrate encouraging results for a variety of diseases including OA. However, their effectiveness needs to be improved. In this review, we selected to discuss the importance of the immunological features of MSCs, including the type of transplantation and the immune and blood compatibility. It is important to consider MSC immune evasive rather than immune privileged. We also highlighted some of the actions/mechanisms that are displayed during tissue healing including the response of MSCs to injury signals, their interaction with the immune system, and the impact of their lifespan. Finally, we briefly summarized the results of clinical studies reporting on the application of MSCs for the treatment of OA. The research field of MSCs is inspiring and innovative but requires more knowledge about the immunobiological properties of these cells. A better understanding of these features will be key for developing a safe and efficient medicinal product for clinical use in OA.

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“…into distinct subsets of tissue macrophages (M1/M2) and function synergistically, but at times counteractively, with other cellular components in a reparative process, orchestrated mainly by the local milieu and cytokine profile (7,8).…”

Section: Ctrp3 Induces An Intermediate Switch Of Cd14 ++ Cd16 + Monocmentioning

confidence: 99%

“…RT-qPCR was performed to determine the mRNA expression levels of IL-6 and TNF-α following the pharmacological treatments. Total RNA of monocytes was isolated using the RNeasy Micro Kit (Qiagen) and complementary DNA was synthesized using the QuantiTect Reverse Transcription Kit (Qiagen) according to the manufacturer's protocol and as previously described (8). The thermocycling conditions were as follows: Initial denaturation for 2 min at 50˚C, and 40 cycles of 10 min at 95˚C and 1.5 min at 60˚C.…”

Section: Assessment Of Phagocytic and Migratory Activitymentioning

confidence: 99%

“…Amplification efficiencies were calculated from the linear part of the quantification curve. Gene expression was normalized to GAPDH and calculated using the 2 -∆∆Cq method (8). Pre-designed Taqman commercial primers (IL-6: Hs00174131_m1; TNF-α, Hs02621508_s1; GAPDH: Hs02786624_g1) were purchased from Thermo Fisher Scientific, Inc. and their efficiency was confirmed in all amplification plots.…”

Section: Assessment Of Phagocytic and Migratory Activitymentioning

confidence: 99%

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CTRP3 induces an intermediate switch of CD14++CD16+ monocyte subset with anti‑inflammatory phenotype

et al. 2020

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Acute myocardial infarction (AMI) evokes a temporally coordinated immune response, in which monocytes are critically involved in the clearance of cell debris; however, excessive inflammation induced by the classical sub-population of monocytes frequently limits the endogenous reparative process. In the present study, the potential of the anti-inflammatory adipokine complement C1q tumor necrosis factor (TNF)-related protein-3 (CTRP3) to induce intermediate switch of monocytes to an anti-inflammatory phenotype was explored. Circulating monocytes were isolated from patients with AMI at various time-points (3-5 h, 3 days and 7 days) and categorized by flow cytometry/immunostaining into three subdivisions based on the expression of CD14 and CD16 epitopes: Classical (CD14 ++ /CD16-), non-classical (CD14 + /CD16 ++) and intermediate populations (CD14 ++ /CD16 +). The phagocytic activity was evaluated by the ingestion of FITC-Zymosan and 19 F-nanoemulsion and the migratory activity using Thin Cert™ Transwell assay. Monocytes were cultured using autologous serum in the presence of CTRP3 (1 µg/ml) for 24 h and the expression of interleukin 6 (IL-6) and TNF-α was quantified by reverse-transcription quantitative PCR. In addition, SB203580, a p38 mitogen-activated protein kinase (MAPK)/ERK inhibitor, was used to examine the downstream pathways of CTRP3. AMI evoked a transient increase in monocyte counts of the classical subset after onset of the ischemic insult, while the non-classical and intermediate subsets persistently expanded (P<0.01). The monocytes from patients at 3 days after AMI displayed enhanced phagocytic and migratory activities in comparison with those from healthy volunteers (P<0.01). Of note, addition of CTRP3 induced an intermediate switch of monocyte subsets and antagonized the enhanced expression of cytokines, particularly IL-6, in monocytes stressed by lipopolysaccharides, likely by blunting the ERK1/2 and P38 MAPK signaling pathway. In conclusion, the present study demonstrated a dynamic fluctuation of monocyte subsets and enhanced phagocytic and migratory activities in patients with AMI. Furthermore, the 'proof-of-concept' evidence pinpoints CTRP3 as an alternative candidate to modulate the 'uncontrolled' inflammatory response and thus to augment cardiac reparative processes in patients with AMI.

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CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity

Cited by 50 publications

References 29 publications

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

Improving the immunosuppressive potential of articular chondroprogenitors in a three-dimensional culture setting

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

CTRP3 induces an intermediate switch of CD14++CD16+ monocyte subset with anti‑inflammatory phenotype

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