Combined use of adipose derived stem cells and TGF-β3 microspheres promotes articular cartilage regeneration in vivo

Directing adipose-derived stem cells (ADSCs) toward chondrogenesis is critical for ADSC-based articular cartilage regeneration. Simvastatin (SIM) was reported to promote both chondrogenic and osteogenic differentiation of ADSCs by upregulating bone morphogenetic protein-2 (BMP-2). We previously found that ADSC chondrogenesis is initiated and promoted in a hyaluronan (HA) microenvironment (HAM). Here, we further hypothesized that SIM augments HAM-induced chondrogenesis but not osteogenesis of ADSCs. ADSCs were treated with SIM in a HAM (SIM plus HAM) by HA-coated wells or HA-enriched fibrin (HA/Fibrin) hydrogel, and chondrogenic differentiation of ADSCs was evaluated. SIM plus HAM increased chondrogenesis more than HAM or SIM alone, including cell aggregation, chondrogenic gene expression (collagen type II and aggrecan) and cartilaginous tissue formation (collagen type II and sulfated glycosaminoglycan). In contrast, SIM-induced osteogenesis in ADSCs was reduced in SIM plus HAM, including mRNA expression of osteogenic genes, osteocalcin and alkaline phosphatase (ALP), ALP activity and mineralization. SIM plus HAM also showed the most effective increases in the mRNA expression of BMP-2 and transcription factors of SOX-9 and RUNX-2 in ADSCs, while these effects were reversed by CD44 blockade. HAM suppressed the levels of JNK, p-JNK, P38 and p-P38 in ADSCs, and SIM plus HAM also decreased SIM-induced phosphorylated JNK and p38 levels. In addition, SIM enhanced articular cartilage regeneration, as demonstrated by implantation of an ADSCs/HA/Fibrin construct in an ex vivo porcine articular chondral defect model. The results from this study indicate that SIM may be an enhancer of HAM-initiated MSC-based chondrogenesis and avoid osteogenesis.

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State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products

Journal of Tissue Engineering and Regenerative Medicine ◽

10.1002/term.386 ◽

2011 ◽

Vol 5 (4) ◽

pp. e36-e51 ◽

Cited By ~ 60

Author(s):

F. Hildner ◽

C. Albrecht ◽

C. Gabriel ◽

H. Redl ◽

M. van Griensven

Keyword(s):

Stem Cells ◽

Articular Cartilage ◽

State Of The Art ◽

Cartilage Regeneration ◽

Adipose Derived Stem Cells ◽

Future Perspectives ◽

Articular Cartilage Regeneration

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Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.606890 ◽

2021 ◽

Vol 9 ◽

Author(s):

Isabele Camargo Brindo da Cruz ◽

Ana Paula Pereira Velosa ◽

Solange Carrasco ◽

Antonio dos Santos Filho ◽

Jurandir Tomaz de Miranda ◽

...

Keyword(s):

Stem Cells ◽

Articular Cartilage ◽

Fas Ligand ◽

Cartilage Regeneration ◽

Type Ii Collagen ◽

Adipose Derived Stem Cells ◽

Type V ◽

Rabbit Articular Cartilage

Collagen is essential for cartilage adhesion and formation. In the present study, histology, immunofluorescence, morphometry, and qRT-PCR suggested that adipose-derived stem cells (ADSCs) stimulated by type V collagen (Col V) induce a significant increase of type II collagen (Col II) in the degenerative area of surgical-induced osteoarthritic rabbit articular cartilage (OA). In vitro, the effects of Col V on the proliferation and differentiation of ADSC were investigated. The expression of the cartilage-related genes Col2a1 and Acan was significantly upregulated and Pou5fl was downregulated post-ADSC/Col V treatment. Post-ADSC/Col V treatment, in vivo analyses revealed that rabbits showed typical signs of osteoarthritic articular cartilage regeneration by hematoxylin and eosin (H&E) and Safranin O/Fast Green staining. Immunohistochemical staining demonstrated that the volume of Col II fibers and the expression of Col II protein were significantly increased, and apoptosis Fas ligand positive significantly decreased post-ADSC/Col V treatment. In conclusion, the expression of Col II was higher in rabbits with surgical-induced osteoarthritic articular cartilage; hence, ADSC/Col V may be a promising therapeutic target for OA treatment.

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Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.815.345 ◽

2013 ◽

Vol 815 ◽

pp. 345-349 ◽

Cited By ~ 2

Author(s):

Ching Wen Hsu ◽

Ping Liu ◽

Song Song Zhu ◽

Feng Deng ◽

Bi Zhang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Growth Factor ◽

Cartilage Defect ◽

Cartilage Regeneration ◽

Tissue Growth ◽

Cartilage Defects

Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

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Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin

Bone and Joint Research ◽

10.1302/2046-3758.62.bjr-2016-0188.r1 ◽

2017 ◽

Vol 6 (2) ◽

pp. 98-107 ◽

Cited By ~ 21

Author(s):

D. Kazemi ◽

K. Shams Asenjan ◽

N. Dehdilani ◽

H. Parsa

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Cartilage Regeneration ◽

Platelet Rich Fibrin ◽

Articular Cartilage Regeneration

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Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

Stem Cells International ◽

10.1155/2018/1073705 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Mohammed Zayed ◽

Steven Newby ◽

Nabil Misk ◽

Robert Donnell ◽

Madhu Dhar

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Articular Cartilage ◽

Synovial Fluid ◽

Cartilage Repair ◽

Cartilage Regeneration ◽

Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

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