Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks

Kronemberger, Gabriela S.; Matsui, Renata Akemi Morais; Miranda, Guilherme de Almeida Santos de Castro E; Granjeiro, José Mauro; Baptista, Leandra Santos

doi:10.4252/wjsc.v12.i2.110

Cited by 40 publications

(26 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we observed that the spheroid form of Ad-MSCs was an ideal treatment candidate for slowing the progression of OA. This could be due to the resemblance of the spheroid to mesenchymal condensation, which is the first stage in the development of cartilage; moreover, MSC spheroids have an increased expression of crucial extracellular matrix (ECM) markers, such as collagen II, collagen IX, aggrecan, tenascin-C, and the cartilage oligomeric matrix [ 43 ]. Four weeks after treatment with matrilin-3-primed Ad-MSC spheroids, the cartilage only showed a roughened articular surface, fibrillation extending to the superficial layer, and a loss of lamina, and it recovered with no structural lesions and loss of safranin-O staining at only eight weeks when compared with the other groups.…”

Section: Discussionmentioning

confidence: 99%

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy

Muttigi

Kim

Choi

et al. 2020

IJMS

View full text Add to dashboard Cite

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-β, 1–14 days) and thyroid hormone hypertrophic medium (T3, 15–28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-β2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs’ therapeutic effect on cartilage regeneration and hypertrophy suppression.

show abstract

Section: Discussionmentioning

confidence: 99%

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy

Muttigi

Kim

Choi

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…ASCs are a heterogeneous population of cells that are harvested from subcutaneous adipose tissue and exhibit several distinct translational advantages over MSCs from other tissues. 45 ASCs have multilineage potential comparable to that of BMSCs, 46 , 47 but they are easily accessible in abundant quantities by a minimally invasive procedure 48 , 49 and have a higher proliferative capacity. 50 ASCs have shown the ability to recapitulate ECO in vitro and in vivo.…”

Section: Engineering Strategies For the In Vitro Recapitulation Of Ecmentioning

confidence: 99%

“… 185 By integrating the principles of “bottom-up” tissue engineering and “developmental engineering” approaches, endochondrally primed spheroids derived from MSCs or ESCs can spontaneously fuse with each other and recapitulate ECO events, making them ideal building blocks for engineering large-scale bone grafts. 49 This integrated approach has several advantages that may support its clinical translation: (1) the possibility of scaling up tissue-engineered bone grafts to a clinically relevant size; (2) the ability to create endochondral bone tissues with high cellular densities without scaffolds; and (3) the potential to model an endochondral bone graft with a complex geometric shape. The engineering of endochondral constructs via cell aggregates 60 , 61 and pellets 72 , 173 has been reported in the studies regarding critical-sized bone defect reconstruction and large bone graft prefabrication.…”

Section: Future Perspectivesmentioning

confidence: 99%

Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

Liu

Yan

et al. 2021

J Tissue Eng

View full text Add to dashboard Cite

Traditional bone tissue engineering (BTE) strategies induce direct bone-like matrix formation by mimicking the embryological process of intramembranous ossification. However, the clinical translation of these clinical strategies for bone repair is hampered by limited vascularization and poor bone regeneration after implantation in vivo. An alternative strategy for overcoming these drawbacks is engineering cartilaginous constructs by recapitulating the embryonic processes of endochondral ossification (ECO); these constructs have shown a unique ability to survive under hypoxic conditions as well as induce neovascularization and ossification. Such developmentally engineered constructs can act as transient biomimetic templates to facilitate bone regeneration in critical-sized defects. This review introduces the concept and mechanism of developmental BTE, explores the routes of endochondral bone graft engineering, highlights the current state of the art in large bone defect reconstruction via ECO-based strategies, and offers perspectives on the challenges and future directions of translating current knowledge from the bench to the bedside.

show abstract

“…Stacking, rolling and folding of these monolayer sheets is the basis to create combined three-dimensional assemblies, including multicellular and pre-vascularized constructs [ 23 , 24 ]. By using cellular spheroids, often made of mesenchymal stem cells, as scaffold-free building blocks, processes like cell-cell and cell-ECM interactions, differentiation and fusion are recapitulated [ 25 , 26 ]. In addition, genetic or chemical engineering of the cell surface allows control over cellular behavior and assembly into higher-order structures [ 27 , 28 ].…”

Section: Tissue Engineering Approachesmentioning

confidence: 99%

Silk-Based Materials for Hard Tissue Engineering

2021

View full text Add to dashboard Cite

Hard tissues, e.g., bone, are mechanically stiff and, most typically, mineralized. To design scaffolds for hard tissue regeneration, mechanical, physico-chemical and biological cues must align with those found in the natural tissue. Combining these aspects poses challenges for material and construct design. Silk-based materials are promising for bone tissue regeneration as they fulfill several of such necessary requirements, and they are non-toxic and biodegradable. They can be processed into a variety of morphologies such as hydrogels, particles and fibers and can be mineralized. Therefore, silk-based materials are versatile candidates for biomedical applications in the field of hard tissue engineering. This review summarizes silk-based approaches for mineralized tissue replacements, and how to find the balance between sufficient material stiffness upon mineralization and cell survival upon attachment as well as nutrient supply.

show abstract

Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks

Cited by 40 publications

References 117 publications

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy

Matrilin-3-Primed Adipose-Derived Mesenchymal Stromal Cell Spheroids Prevent Mesenchymal Stromal-Cell-Derived Chondrocyte Hypertrophy

Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

Silk-Based Materials for Hard Tissue Engineering

Contact Info

Product

Resources

About