Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair
Abstract
:1. Introduction
2. Adipose-Derived Mesenchymal Stromal Cells (ASCs)
2.1. ASC Osteogenic Differentiation
2.2. ASC Chondrogenic Differentiation
3. ASC-Based Repair Strategies
Scaffold-Assisted Strategies
4. Bone Repair
Scaffold-Assisted ASC Implantations
5. Cartilage Repair
Scaffold-Assisted ASC Implantations
6. Osteochondral Defect Repair
Scaffold-Assisted ASC Implantations
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALP | alkaline phosphatase |
ASCs | adipose-derived MSCs |
BMP | bone morphogenetic protein |
BMSCs | bone marrow stromal cells |
ECM | extracellular matrix |
ELISA | enzyme-linked immunosorbent assay |
FGF | fibroblast growth factor |
IGF-1 | insulin-like growth factor 1 |
MSCs | mesenchymal stromal cells |
OA | osteoarthritis |
OC | osteochondral |
PCL | polycaprolactone |
PCR | polymerase chain reaction |
PDGF | platelet-derived growth factor |
PLGA | polylactic-co-glycolic acid |
PLA | polylactic acid |
PRP | platelet-rich plasma |
RUNX2 | runt-related transcription factor 2 |
SOX 9 | sex-determining region Y box 9 |
SVF | stromal vascular fraction |
TCP | tricalcium phosphate |
TGF-β | transforming growth factor beta |
TNF | tumor necrosis factor |
VEGF | vascular endothelial growth factor |
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Cells | Study Design | Outcomes | References |
---|---|---|---|
ASCs overexpressing basic FGF | Intramuscular injection in a mouse model of femur fracture | Improved ASC engrafting, mineralization activity, angiogenesis and osteogenic differentiation. Accelerated bone repair | [68] |
ASCs predifferentiated toward osteogenic linage and endothelial precursor cells | Subcutaneous implantation of osteogenic cell sheet and endothelial progenitor cell complexes in nude mice | Dense new ectopic bone tissue formation | [70] |
Implantation of osteogenic cell sheet and endothelial progenitor cell complexes in rabbits with calvarial defects | Satisfactory bone tissue reconstruction | ||
ASCs from osteoporotic mice and ASCs from healthy mice | Osteogenic differentiation in vitro of ASCs | Lower proliferation rate and osteogenic differentiation ability by osteoporotic ASCs | [40] |
ASCs from aged and young mouse | In vitro tests of proliferation rate and osteogenic differentiation | Higher proliferation rate and differentiation ability by young ASCs | [71] |
Injection in bone marrow of osteoporotic mice | Improved bone regeneration and increased bone mineral density by young ASCs | ||
ASCs and/or BMSCs | Injections in rat calvarial defects | Improved bone formation, especially for injections of both cells | [72,73] |
Fibrin-encapsulated ASCs in printed PCL scaffolds | TNF-α and PDGF treatment in osteogenic and vasculogenic medium | Improved new vessel formation and matrix mineralization at low doses of TNF-α | [76] |
Subcutaneous implant in athymic nude rats | Improved angiogenesis and bone tissue maturation | ||
Scaffold-assisted implantation of native or predifferentiated ASCs | Subcutaneous implantation in mice | Enhanced ectopic bone formation | [42,74,77,78,83] |
Titanium scaffolds coated with cell matrix hydrogel ASCs | Implantation in a rat model of full-thickness mandibular defects | Improved bone regeneration and new bone formation | [85] |
ASCs in 3D-printed PCL/TCP scaffolds functionalized with bone ECM | Implantation in dogs with mandibular defects | More pronounced ossification | [86] |
ASCs in PRP/collagen scaffolds | Injection in mandibular osteoradionecrosis model of athymic rats | Enhanced bone preservation and deposition along with increased osteoblasts and decreased osteoclasts | [87] |
Engineered ASCs for BMP-2 and/or VEGF release seeded in acellular bone matrix | Implantation in ulnar bone defects of minipigs | Accelerated repair of bone defects | [88] |
Engineered ASCs overexpressing osterix in gelatin/VEGF-coated PCL scaffolds | Implantation in rats with calvarial defect | Improved ASC osteogenesis and bone repair | [90] |
ASCs in gelatin microribbon-based microporous hydrogel supplemented with BMP-2 | Injection in a mouse model of cranial defect | Enhanced ASC survival and good filling of the bone defect | [91] |
Indirect cocultures of ASCs and osteoblasts in collagen-based 3D scaffolds | Implantation in rats with calvarial defects | Good levels of new bone formation and coverage ratio | [92] |
ASCs seeded in methacrylated gelatin hydrogels | Effects of photobiomodulation on scaffold implantation in rats with biparietal bone defects | Significantly improved reconstruction of bone defects | [93] |
ECM hydrogel supplemented with ASC-derived exosomes | Injection in a rat model of intervertebral disc degeneration | ECM regeneration along with decreased ECM catabolism and reduced metalloprotease activity | [94] |
Autologous ASCs | Autograft in oncology patients and in patients with nonunion bone fractures | Verified procedure safety and ASC clinical efficacy | [95] |
Osteoinducted ASCs and demineralized bone matrix | Transplantation in patients with long bone nonunion or tumor resection | Improved osteogenesis, re-established bone function with no significant adverse side effects | [96] |
Cells | Study Design | Outcomes | References |
---|---|---|---|
SVF cells and PRP | Injection into the knee of OA mouse model | Improved regeneration of injured articular cartilage and joint movement | [101] |
ASCs | Injection into the knee of OA rabbit model | Significant improvements in the quality of cartilage | [102] |
Engineered ASCs to overexpress IGF-1 | In vitro experiments | Overexpression of chondrocyte anabolic markers | [103] |
Injection into the knee of OA mouse model | Increased ASC survival and reduced cartilage degeneration | ||
Chondrocyte-like differentiated ASCs | Injection into the knee of OA rat model | Enhanced hyaline-like neocartilage formation and fibrosis reduction | [49] |
ASCs or SVF cells in collagen I/III scaffolds | Implantation in Dutch milk goats with cartilage defects of medial condyles and trochlear grooves of the knee | Extensive expression of collagen type II, hyaline-like cartilage. High levels of regenerated subchondral bone | [104] |
Autologous ASCs combined with hyaluronic acid, PRP and calcium chloride | Percutaneous injection in the knee of OA patients and into the femoral head of patients with osteonecrosis | Improved cartilage regeneration in OA patients. Improved bone formation in patients with osteonecrosis | [106] |
Autologous ASCs | Intra-articular injection in the knee of OA patients | Pain relief and improved joint function without serious adverse events | [107,108] |
Chondrocyte-like differentiated ASCs in cartilage-based scaffolds | Implantation in the knee of rabbits with cartilage defects | Defect filling with chondrocyte-like tissue with smooth surface, showing collagen type II expression and positive Alcian blue staining | [100] |
ASCs in cartilage-based scaffolds | Implantation in the knee of rabbits with cartilage defects | Improved chondrogenic differentiation. Good levels of hyaline cartilage regeneration | [109] |
ASCs or ASC secretome in biodegradable porous sponge cartilage scaffolds | Implantation in rabbits with femoral trochlea cartilage damage | Enhanced cartilage regeneration better achieved by ASCs than secretome | [110] |
ASCs in calcium alginate gel | Implantation in a full-thickness hyaline cartilage defect at the patellofemoral joint in rabbits | Complete cartilage repair | [111] |
ASCs in amnion membrane-based biomimetic injectable hydrogel | Intra-articular injection in OA rat model | Reduced inflammation. Improved chondroprotective effects and cartilage regeneration | [112] |
Cells | Study Design | Outcomes | References |
---|---|---|---|
3D scaffold-free constructs of autologous ASCs | Implantation in the patellofemoral groove of minipig models of OC defects | Increased hyaline cartilage formation and improved subchondral bone regeneration | [117] |
3D scaffold-free constructs of allogeneic ASCs | Implantation in the trochlear groove of the knee in rabbit models of OC defects | Improved articular cartilage and subchondral bone regeneration | [119] |
3D scaffold-free concentric bicylindrical constructs of autologous ASCs | Implantation in minipigs with OC defects in the groove of the knee | Improved tissue repair | [120] |
Chondrocyte-like ASCs in chitosan/gelatin hydrogel. Osteoblast-like ASCs in cancellous bone | In vitro assembly of 3D bilayered scaffolds for simultaneous bone and cartilage regeneration | Enhanced ASC proliferation compared with cells seeded on either single scaffold | [121] |
Chondrocyte-like ASCs and osteocyte-like ASCs in poly(l-glutamic acid)-based 3D bilayer scaffolds | Implantation in rabbit model with OC defects in the patellofemoral groove of the knee | Improved simultaneous cartilage and subchondral bone tissue regeneration | [122] |
3D bilayer scaffolds with an electrospun disk separating superficial chondrocyte-like ASCs in decellularized bovine cartilage ECM and underlying osteoblast-like ASCs in PCL/TCP | Implantation in OC defects in the trochlear groove of minipigs | Good levels of defect filling mainly by subchondral bone. Limited cartilage repair in the superficial part | [123] |
3D bilayer scaffolds consisting of HA and gelatin-based microcryogels, seeded with umbilical cord blood MSCs | Implantation in OC defects in the femoral trochlear groove of dogs | Satisfactory levels of defect filling with newly formed cartilage and bone tissue | [9] |
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Romano, I.R.; D’Angeli, F.; Vicario, N.; Russo, C.; Genovese, C.; Lo Furno, D.; Mannino, G.; Tamburino, S.; Parenti, R.; Giuffrida, R. Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair. Biomedicines 2023, 11, 1781. https://doi.org/10.3390/biomedicines11071781
Romano IR, D’Angeli F, Vicario N, Russo C, Genovese C, Lo Furno D, Mannino G, Tamburino S, Parenti R, Giuffrida R. Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair. Biomedicines. 2023; 11(7):1781. https://doi.org/10.3390/biomedicines11071781
Chicago/Turabian StyleRomano, Ivana Roberta, Floriana D’Angeli, Nunzio Vicario, Cristina Russo, Carlo Genovese, Debora Lo Furno, Giuliana Mannino, Serena Tamburino, Rosalba Parenti, and Rosario Giuffrida. 2023. "Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair" Biomedicines 11, no. 7: 1781. https://doi.org/10.3390/biomedicines11071781