Donor-matched mesenchymal stem cells from knee infrapatellar and subcutaneous adipose tissue of osteoarthritic donors display differential chondrogenic and osteogenic commitment.
Cell-based therapies have recently been proposed for the treatment of degenerative articular pathologies, such as early osteoarthritis, with an emphasis on autologous mesenchymal stem cells (MSCs), as an alternative to terminally differentiated cells. In this study, we performed a donor-matched comparison between infrapatellar fat pad MSCs (IFP-MSCs) and knee subcutaneous adipose tissue stem cells (ASCs), as appealing candidates for cell-based therapies that are easily accessible during surgery. IFP-MSCs and ASCs were obtained from 25 osteoarthritic patients undergoing total knee replacement and compared for their immunophenotype and differentiative potential. Undifferentiated IFP-MSCs and ASCs displayed the same immunophenotype, typical of MSCs (CD13+/CD29+/CD44+/CD73+/CD90+/CD105+/CD166+/CD31-/CD45-). IFP-MSCs and ASCs showed similar adipogenic potential, though undifferentiated ASCs had higher LEP expression compared to IFP-MSCs (p<0.01). Higher levels of calcified matrix (p<0.05) and alkaline phosphatase (p<0.05) in ASCs highlighted their superior osteogenic commitment compared to IFP-MSCs. Conversely, IFP-MSCs pellets showed greater amounts of glycosaminoglycans (p<0.01) and superior expression of ACAN (p<0.001), SOX9, COMP (p<0.001) and COL2A1 (p<0.05) compared to ASCs pellets, revealing a superior chondrogenic potential. This was also supported by lower COL10A1 (p<0.05) and COL1A1 (p<0.01) expression and lower alkaline phosphatase release (p<0.05) by IFP-MSCs compared to ASCs. The observed dissimilarities between IFP-MSCs and ASCs show that, despite expressing similar surface markers, MSCs deriving from different fat depots in the same surgical site possess specific features. Furthermore, the in vitro peculiar commitment of IFP-MSCs and ASCs from osteoarthritic donors towards the chondrogenic or osteogenic lineage may suggest a preferential use for cartilage and bone cell-based treatments, respectively.
Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161 Milan, Italy.matteo.moretti@grupposandonato.it.
S
S
Lopa
A
A
Colombini
D
D
Stanco
L
L
de Girolamo
V
V
Sansone
M
M
Moretti
D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020219:Chondrogenesis; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology*; D010012:Osteogenesis; D010329:Patella / Q000166:cytology / Q000473:pathology*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014019:Tissue Donors
D053674:Aggrecans; D000469:Alkaline Phosphatase; D015703:Antigens, CD; D002118:Calcium; D064236:Cartilage Oligomeric Matrix Protein; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024121:Collagen Type X; D006025:Glycosaminoglycans; D020738:Leptin; D055758:SOX9 Transcription Factor; C508319:ACAN protein, human; C527932:SOX9 protein, human; C020341:glucosaminoglycans; C577553:TSP5 protein, human