Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma.
The human adult stem cells from bone marrow stroma referred to as mesenchymal stem cells or marrow stromal cells (MSCs) are of interest because they are easily isolated and expanded and are capable of multipotential differentiation. Here, we examined the ability of recombinant human bone morphogenetic protein (BMP)-2, -4, and -6 to enhance in vitro cartilage formation of MSCs. Human MSCs were isolated from bone marrow taken from normal adult donors. The cells were pelleted and cultured for 21 days in chondrogenic medium containing transforming growth factor beta3 and dexamethasone with or without BMP-2, -4, or -6. All the BMPs tested increased chondrogenic differentiation as assayed by immunohistochemistry and by the size and weight of the cartilage synthesized. However, BMP-2 was the most effective. Microarray analyses of approximately 12,000 genes and reverse transcription-polymerase chain reaction assays established that the critical genes for cartilage synthesis were expressed in the expected time sequence in response to BMP-2. The tissue engineering of autologous cartilage derived from MSCs in vitro for transplantation will be a future alternative for patients with cartilage injuries. To obtain large amounts of cartilage rich in proteoglycans, the use of BMP-2 is recommended, instead of BMP-4 or -6.
Sekiya
Ichiro
I
Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, LA 70112-2699, USA.
Larson
Benjamin L
BL
Vuoristo
Jussi T
JT
Reger
Roxanne L
RL
Prockop
Darwin J
DJ
D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D002356:Cartilage / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D053782:Transforming Growth Factor beta3
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525816:BMP6 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D003470:Culture Media; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D003907:Dexamethasone