Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate

Huang, Zhao; Nooeaid, Patcharakamon; Kohl, Benjamin; Roether, Judith A.; Schubert, Dirk W.; Meier, Carola; Boccaccını, Aldo R.; Godkin, Owen; Ertel, Wolfgang; Arens, Stephan; Schulze‐Tanzil, Gundula

doi:10.1016/j.msec.2015.01.082

Cited by 34 publications

(31 citation statements)

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“…of studiesReferencesCell SourceNo. of studies a ReferencesHuman73[48, 50, 52, 53, 168–236]Bone marrow62[48, 50–53, 164, 168, 170–173, 177–180, 182–185, 187, 188, 192, 195–197, 203, 206–210, 212, 216, 217, 219, 221, 223, 227, 230, 232–235, 237–255]Rabbit17[240–242, 246, 249, 252, 255–265]Adipose36[66, 169, 175, 176, 181, 186, 189, 193, 194, 199, 201, 202, 211, 214, 216, 218–220, 224, 228, 229, 231, 235, 242, 256, 257, 260–269]Bovine5[51, 164, 243, 245, 270]Synovium9[174, 191, 200…”

Section: Resultsmentioning

confidence: 99%

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

et al. 2017

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BackgroundThe management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects.Main body of abstractThis review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous.Short conclusionsThis review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place.

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Section: Resultsmentioning

confidence: 99%

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

et al. 2017

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“…Adherent cells were grown to sufficient numbers for the experiment performance by regular passaging at passages 3-4. The cell surface protein expression profile of the isolated MSCs was characterized previously [Huang et al, 2015]. Two days after reseeding, before chondrogenic induction, the scaffolds were cultured for 24 h in EM6F with 20 μmol/l azacytidine (Sigma-Aldrich).…”

Section: Isolation Culture and Chondrogenic Induction Of Hbm-mscsmentioning

confidence: 99%

Establishment of a Cytocompatible Cell-Free Intervertebral Disc Matrix for Chondrogenesis with Human Bone Marrow-Derived Mesenchymal Stromal Cells

Huang¹,

Kohl²,

Kokozidou³

et al. 2016

Cells Tissues Organs

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Tissue-engineered intervertebral discs (IVDs) utilizing decellularized extracellular matrix (ECM) could be an option for the reconstruction of impaired IVDs due to degeneration or injury. The objective of this study was to prepare a cell-free decellularized human IVD scaffold and to compare neotissue formation in response to recellularization with human IVD cells (hIVDCs) or human bone marrow-derived (hBM) mesenchymal stromal cells (MSCs). IVDs were decellularized via freeze-thaw cycles, detergents and trypsin. Histological staining was performed to monitor cell removal and glycosaminoglycan (GAG) removal. The decellularized IVD was preconditioned using bovine serum albumin and fetal bovine serum before its cytocompatibility for dynamically cultured hBM-MSCs (chondrogenically induced or not) and hIVDCs was compared after 14 days. In addition, DNA, total collagen and GAG contents were assessed. The decellularization protocol achieved maximal cell removal, with only few remaining cell nuclei compared with native tissue, and low toxicity. The DNA content was significantly higher in scaffolds seeded with hIVDCs compared with native IVDs, cell-free and hBM-MSC-seeded scaffolds (p < 0.01). The GAG content in the native tissue was significantly higher compared to the others groups except for the scaffolds reseeded with chondrogenically induced hBM-MSCs (p < 0.05). In addition, there was a significantly increased total collagen content in the chondrogenically induced hBM-MSCs group (p < 0.01) compared with the native IVDs, cell-free and hIVDC-seeded scaffolds (p < 0.01); both recolonizing cell types were more evenly distributed on the scaffold surface, but only few cells penetrated the scaffold. The resulting decellularized ECM was cytocompatible and allowed hBM-MSCs/hIVDCs survival and ECM production.

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“…However, at higher concentration of CS, a decreased Young's modulus was observed. Zhao Huang et al indicated the incorporation of CS signi cantly increased the storage modulus of the Alg-foams [33].…”

Section: Discussionmentioning

confidence: 99%

“…Alg has been extensively studied in biomedical applications especially in tissue engineering owing to the biocompatibility, non-toxicity, nonimmunogenicity, good gel forming ability and low cost [28,29,31]. Previous studies indicated Alg hydrogel provides an optimal milieu for chondrogenic differentiation of encapsulated MSCs [30,[32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Hypertrophy and Improving Chondrocyte Differentiation by MMP-13 Inhibitor Small Molecule-Encapsulated in Alginate-Chondroitin Sulfate-Platelet Lysate Hydrogel

Jahangir

Eglin²,

Pötter

et al. 2020

Preprint

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Background Mesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix Metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event. MMP-13 is a collagen degrading enzyme, which is also highly expressed in the hypertrophic zone of the growth plate and in OA cartilage. Accordingly, we investigated the effect of MMP-13 inhibition on MSC hypertrophy.Methods In this study, 5-bromoindole-2-carboxylic acid (BICA) was used as an inhibitory agent for MMP-13 expression. After identifying its optimal concentration, BICA was mixed into a hydrogel and the release rate was studied. To prepare the ideal hydrogel, chondroitin sulfate (CS) and platelet lysate (PL) were mixed with sodium alginate (Alg) at concentrations selected based on synergistic mechanical and rheometric properties. Then, four hydrogels were prepared by combining alginate (1.5%w/v), and/or CS (1%w/v) and/or PL (20%v/v). The chondrogenic potential and progression to hypertrophy of human bone marrow-derived mesenchymal stem cell (hBM-MSC) loaded hydrogels were investigated under free swelling and mechanical loading conditions, in the presence and absence of BICA.Results Viability of hBM-MSCs seeded in the four hydrogels was similar. qRT-PCR revealed that BICA could successfully inhibit MMP-13 expression, which led to an inhibition of Coll X and induction of Coll-II, in both free swelling and loading conditions. The GAG deposition was higher in the group combining BICA and mechanical stimulation.Conclusions It is concluded that BICA inhibition of MMP-13 reduces MSC hypertrophy during chondrogenesis.

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Chondrogenesis of human bone marrow mesenchymal stromal cells in highly porous alginate-foams supplemented with chondroitin sulfate

Cited by 34 publications

References 65 publications

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

Establishment of a Cytocompatible Cell-Free Intervertebral Disc Matrix for Chondrogenesis with Human Bone Marrow-Derived Mesenchymal Stromal Cells

Inhibition of Hypertrophy and Improving Chondrocyte Differentiation by MMP-13 Inhibitor Small Molecule-Encapsulated in Alginate-Chondroitin Sulfate-Platelet Lysate Hydrogel

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