Delayed release of chemokine CCL25 with bioresorbable microparticles for mobilization of human mesenchymal stem cells

Fröhlich, Kristin; Hartzke, David; Schmidt, Franziska; Eucker, Jan; Gurlo, Aleksander; Sittinger, Michael; Ringe, Jochen

doi:10.1016/j.actbio.2018.01.036

Cited by 8 publications

(9 citation statements)

References 50 publications

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“…To avoid the long and costly culture period, we proposed a one‐step in situ repair approach using a potential trigger for recruitment of endogenous MSC into the OA side and thereby enhance regeneration. The results of this and other studies suggest that the chemokine CCL25 affects the migration of MSC. We were able to detect an average of 85 pg/ml (0.007 nM) CCL25 in the SF of 11‐month‐old guinea pigs.…”

Section: Discussionsupporting

confidence: 69%

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CCL25‐Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis

Ringe

Hemmati‐Sadeghi

Fröhlich

et al. 2019

Journal Orthopaedic Research

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There is evidence that the application of mesenchymal stromal cells (MSCs) counteracts osteoarthritis (OA) progression. However, the prospect of extracting and expanding these cells might be limited. The aim of this study was to investigate whether hyaluronic acid (HA) supplemented with MSC-recruiting chemokine C-C motif ligand 25 (CCL25) can influence the natural course of spontaneous OA in the guinea pig. CCL25 concentration in synovial fluid (SF) was quantified with enzyme-linked immunosorbent assay. Boyden chamber cell migration assay was used to test CCL25-mediated migration of guinea pig MSC. Forty-nine 11-month-old male guinea pigs were divided into seven groups. The main treatments consisted of five intra-articular injections of HA in pure form and in combination with three doses of CCL25 (63, 693, and 6,993 pg) given at a weekly interval. The severity of cartilage damage was assessed by using a modified Mankin score. The measured average physiological concentration of CCL25 in SF of animals is 85 ± 39 pg/ml. MSC showed a 3.2-fold increase in cell migration at 1,000 nM CCL25 in vitro demonstrating the biological migratory activity of CCL25 on these cells. In vivo, treatment with HA alone did not reduce OA progression. Similarly, OA scores were not found significantly reduced after treatment with 63 pg CCL25 + HA. However, when compared to pure HA, treatment with 693 pg CCL25 + HA and 6,993 pg CCL25 + HA significantly reduced the OA score from 10.1 to 7.4 (−28%) and 8.4 (−20%), respectively. These data suggest that intra-articular injections of HA supplemented with CCL25 attenuates OA.

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Section: Discussionsupporting

confidence: 69%

“…Chemokine C‐C motif ligand 25 (CCL25), also known as thymus‐expressed chemokine (TECK), is a chemoattractant that mobilizes human MSC along positive chemokine gradients but does not induce a mobilization away from the gradient . CCL25 operates following binding to the chemokine receptor CCR9 .…”

mentioning

confidence: 99%

CCL25‐Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis

Ringe

Hemmati‐Sadeghi

Fröhlich

et al. 2019

Journal Orthopaedic Research

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“…Double emulsion technique is also operated to obtain MPs and NPs with the water-in-oil-in-water being the most used procedure and PLGA being the most commonly used polymer. A recent study aimed at tailoring PLGA MPs to obtain a controlled delayed release of the cytokine CCL25, a chemoattractant of mesenchymal stem cells (MSCs), by playing on the polymer molecular weight, chemical functionalization, emulsion type and amount of BSA excipient [15]. Another study reported the combination of lipids and PLGA to encapsulate and release lysozyme, showing a better encapsulation efficiency and reduction of burst release of this enzyme with a higher content of PLGA [16].…”

Section: Ii111 Emulsificationmentioning

confidence: 99%

“…chemokine CCL25 [15], neurotrophin-3 [76], vascular endothelial growth factor (VEGF) [100,108], transforming growth factor-β (TGF-β) [20,113], basic fibroblast growth factor (bFGF) [89], β-nerve growth factor (β-NGF) [92]… It is also used for less sensitive proteins such as insulin [93,94], lysozyme [67] and OVA [92].…”

Section: Iii131 Elisamentioning

confidence: 99%

Design and applications of protein delivery systems in nanomedicine and tissue engineering

Bizeau

Mertz

2021

Advances in Colloid and Interface Science

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“…In a recent study, thymus-expressed chemokine (CCL25) was pointed out to be a candidate for in situ tissue engineering [14]. Its chemotactic effect on human bone marrow MSC was shown in Boyden chamber assays, and expression profiling of CCL25 stimulated MSC revealed the induction of genes coding for factors that are involved in the migration and homing of bone marrow cells [15].…”

Section: Introductionmentioning

confidence: 99%

Dose-Dependent Effect of Mesenchymal Stromal Cell Recruiting Chemokine CCL25 on Porcine Tissue-Engineered Healthy and Osteoarthritic Cartilage

Lüderitz

Dehne

Sittinger

et al. 2018

IJMS

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Thymus-expressed chemokine (CCL25) is a potent cell attractant for mesenchymal stromal cells, and therefore it is a candidate for in situ cartilage repair approaches focusing on the recruitment of endogenous repair cells. However, the influence of CCL25 on cartilage is unknown. Accordingly, in this study, we investigated the effect of CCL25 on tissue-engineered healthy and osteoarthritic cartilage. Porcine chondrocytes were cultured in a three-dimensional (3D) micromass model that has been proven to mimic key-aspects of human cartilage and osteoarthritic alterations upon stimulation with tumor necrosis factor-α (TNF-α). Micromass cultures were stimulated with CCL25 (0, 0.05, 0.5, 5, 50, 500 nmol/L) alone or in combination with 0.6 nmol/L TNF-α for seven days. Effects were evaluated by life/dead staining, safranin O staining, histomorphometrical analysis of glycosaminoglycans (GAGs), collagen type II (COL2A1) real-time RT-PCR and Porcine Genome Array analysis. 500 nmol/L CCL25 led to a significant reduction of GAGs and COL2A1 expression and induced the expression of matrix metallopeptidases (MMP) 1, MMP3, early growth response protein 1 (EGR1), and superoxide dismutase 2 (SOD2). In concentrations lower than 500 nmol/L, CCL25 seems to be a candidate for in situ cartilage repair therapy approaches.

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Delayed release of chemokine CCL25 with bioresorbable microparticles for mobilization of human mesenchymal stem cells

Cited by 8 publications

References 50 publications

CCL25‐Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis

CCL25‐Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis

Design and applications of protein delivery systems in nanomedicine and tissue engineering

Dose-Dependent Effect of Mesenchymal Stromal Cell Recruiting Chemokine CCL25 on Porcine Tissue-Engineered Healthy and Osteoarthritic Cartilage

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