Dataset Information

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation^.

ABSTRACT: Chemokine stromal cell-derived factor-1 (SDF-1) is a powerful chemoattractant for the localization of CXCR4-positive bone marrow mesenchymal stem cells (BMSCs) into the bone marrow. We studied the effects of SDF-1 on the cartilage defect repair by recruiting BMSCs and promoting its chondrogenic differentiation in vitro and in vivo. Chemotaxis analysis with Transwell plate showed that SDF-1 could recruit BMSCs through SDF-1/CXCR4 axis. Real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and Western blot results suggested that the levels of type II collagen and GAG were increased after incubating BMSCs with SDF-1 compared with the without SDF-1 group. More positive BrdU-labeled BMSCs were detected at the cartilage defect region in the SDF-1 + poly [lactide-co-glycolide] (PLGA) scaffold group (SP) in which those animals showed a smooth and transparent cartilage tissue with a strong staining of toluidine blue and type II collagen compared with the no-SDF-1 groups. ICRS score suggested that the repair effect in the SDF-1 + PLGA-treated animals was improved compared with PLGA scaffold group alone at 4 and 8 weeks after surgery; the repair effect from the SDF + PLGA-treated animals was significantly improved compared with the PLGA alone at 12 weeks after surgery. Our in vitro and in vivo results indicated the following: (1) SDF-1 could recruit the BMSCs into cartilage defect area. (2) SDF-1 induces BMSCs expressing type II collagen and GAG, which may accelerate the BMSCs transforming into chondrocytes under the cartilage microenvironment in vivo. (3) PLGA scaffold attached with SDF-1 remarkably promoted the cartilage defect repairing. The defected cartilage was filled with transparent cartilage 12 weeks after the surgery, which shared a similar structure with the adjacent normal cartilage. Taken together, this research provides a new strategy for cartilage defect repairing.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6037190 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation<sup/>.

Wang Yuze Y Sun Xiaojuan X Lv Jia J Zeng Lingyuan L Wei Xiaochun X Wei Lei L

Tissue engineering. Part A 20170926 19-20

Chemokine stromal cell-derived factor-1 (SDF-1) is a powerful chemoattractant for the localization of CXCR4-positive bone marrow mesenchymal stem cells (BMSCs) into the bone marrow. We studied the effects of SDF-1 on the cartilage defect repair by recruiting BMSCs and promoting its chondrogenic differentiation in vitro and in vivo. Chemotaxis analysis with Transwell plate showed that SDF-1 could recruit BMSCs through SDF-1/CXCR4 axis. Real-time polymerase chain reaction, enzyme-linked immunosorb ...[more]

PMID: 28478702

Similar Datasets

Project description:Background:Mesenchymal stem cells (MSCs) can be easily expanded without losing the ability of multilineage differentiation, including oesteogenic, chondrogenic and adipogenic differentiation. These characters make MSCs a promising cell resource for cartilage defect repair. MSCs could be recruited by inflammatory stimulation, then home to the injury tissues. However, its capacity of homing is extremely limited. Thus, it has become extremely necessary to develop an agent or a method, which can be used to enhance the efficiency of MSCs homing. This study investigates the effect of stearic acid methyl ester (SAME) on MSCs mobilisation and cartilage regeneration. Methods:MSCs were isolated from femurs of Sprague-Dawley (SD) rats. MTT assay was used to detect effect of SAME on viability of MSCs. Transwell assay and wound healing assay were used to detect effect of SAME on migration of MSCs. RNA-seq, quantitative real-time PCR and western blot were performed to analyze the expression of RNAs and proteins. Colony forming assay and flow cytometry were used to evaluate the effect of SAME on MSCs mobilisation in vivo. A rat cartilage defect model was created to evaluate the effect of SAME on cartilage regeneration. Results:We found that SAME could promote the migration of MSCs. Interestingly, we found SAME significantly increased the expression levels of Vav1 in MSCs. On the other hand, the enhanced migration ability of MSCs induced by SAME was retarded by Vav1 small interfering RNA (siRNA) and Rho-associated protein kinase 2 (ROCK2) inhibitor. In addition, we also checked the effect of SAME on mobilisation of MSCs in vivo. The results showed that SAME increased the number of MSCs in peripheral blood and enhanced the capacity of colony formation. Finally, using a cartilage defect model in rats, we found SAME could improve cartilage repair. Conclusion:Our study demonstrates that SAME can enhance MSCs migration ability mainly through the Vav1/ROCK2 signaling pathway, which could contribute to the accelerated cartilage regeneration. The translational potential of this article:These findings provide evidence that SAME could be used as a therapeutic reagent for MSCs mobilisation and cartilage regeneration.

Project description:Cartilage has little intrinsic capacity for repair, so transplantation of exogenous cartilage cells is considered a realistic option for cartilage regeneration. We explored whether human-induced pluripotent stem cells (hiPSCs) could represent such unlimited cell sources for neo-cartilage comparable to human primary articular chondrocytes (hPACs) or human bone marrow-derived mesenchymal stromal cells (hBMSCs). For this, chondroprogenitor cells (hiCPCs) and hiPSC-derived mesenchymal stromal cells (hiMSCs) were generated from two independent hiPSC lines and characterized by morphology, flow cytometry, and differentiation potential. Chondrogenesis was compared to hBMSCs and hPACs by histology, immunohistochemistry, and RT-qPCR, while similarities were estimated based on Pearson correlations using a panel of 20 relevant genes. Our data show successful differentiations of hiPSC into hiMSCs and hiCPCs. Characteristic hBMSC markers were shared between hBMSCs and hiMSCs, with the exception of CD146 and CD45. However, neo-cartilage generated from hiMSCs showed low resemblances when compared to hBMSCs (53%) and hPACs (39%) characterized by lower collagen type 2 and higher collagen type 1 expression. Contrarily, hiCPC neo-cartilage generated neo-cartilage more similar to hPACs (65%), with stronger expression of matrix deposition markers. Our study shows that taking a stepwise approach to generate neo-cartilage from hiPSCs via chondroprogenitor cells results in strong similarities to neo-cartilage of hPACs within 3 weeks following chondrogenesis, making them a potential candidate for regenerative therapies. Contrarily, neo-cartilage deposited by hiMSCs seems more prone to hypertrophic characteristics compared to hPACs. We therefore compared chondrocytes derived from hiMSCs and hiCPCs with hPACs and hBMSCs to outline similarities and differences between their neo-cartilage and establish their potential suitability for regenerative medicine and disease modelling.

Project description:BackgroundConnective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity.HypothesisThe harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone.Study designControlled laboratory study.MethodsCTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques-BM aspiration and BM collection-after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry.ResultsCells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45-CD271+CD56+ CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD271+CD56+ cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD271+CD56+ cells were localized in the bone-lining regions whereas CD271+CD56- cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD271+CD56+ bone-lining cells in both tissues.ConclusionChondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation.Clinical relevanceThe harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair.

Dataset Information

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation^.

Publications

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation<sup/>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation.

Publications

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation<sup/>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Stromal Cell-Derived Factor-1 Accelerates Cartilage Defect Repairing by Recruiting Bone Marrow Mesenchymal Stem Cells and Promoting Chondrogenic Differentiation^.