Sustained delivery of BMP-2 and platelet-rich plasma-released growth factors contributes to osteogenesis of human adipose-derived stem cells.

Platelet-rich plasma (PRP) has a pool of multiple growth factors efficient at inducing the proliferation and osteogenic differentiation of human adipose-derived stem cells (hADSCs). Bone morphogenetic protein (BMP)-2 is a strong stimulator for the osteogenic differentiation of hADSCs. The purpose of this study was to verify the effect of PRP-released growth factors and microsphere-encapsulated BMP-2 on the proliferation and osteoblastic differentiation of hADSCs and to construct a novel tissue-engineered bone. The BMP-2-loaded microspheres and hADSCs were embedded in activated PRP gel. Another 5 composites (hADSCs/platelet-poor plasma [PPP]; hADSCs/PRP; hADSCs/BMP-2/PPP; hADSCs/BMP-2/PRP; and hADSCs/BMP-2+microspheres/PPP) were also constructed. The DNA content, alkaline phosphatase activity, mRNA expression of alkaline phosphatase, osteopontin, osteocalcin, and mineralization of hADSCs in each composite were compared. The DNA content was higher in all PRP-containing composites, meaning that PRP-released growth factors stimulated proliferation of hADSCs. Alkaline phosphatase increased in BMP-2/PRP and BMP-2+microspheres/PRP composites in the first 7 days, meaning that BMP-2 had a synergistic effect with PRP in the early differentiation of hADSCs. Osteopontin, osteocalcin, and mineralization assays were higher in BMP-2+microspheres/PRP composite than in the BMP-2/PRP composite up to 21 days, meaning that a continuous delivery of BMP-2 stimulates osteoblastic differentiation of hADSCs at the early stage and the final maturation stage. These results suggest that sustained delivery of BMP-2 in combination with PRP is better than a single administration of PRP or BMP-2 in the osteogenic differentiation of hADSCs.

[1]  J. J. Coleman,et al.  The Use of Skin Substitutes in Burns and Non-Healing Wounds , 2010 .

[2]  M. Longaker,et al.  Divergent Modulation of Adipose-Derived Stromal Cell Differentiation by TGF-&bgr;1 Based on Species of Derivation , 2010, Plastic and reconstructive surgery.

[3]  Y. Rasko,et al.  Spontaneous hematoma of the breast 30 years after augmentation. , 2010, Plastic and Reconstructive Surgery.

[4]  M. Longaker,et al.  Regulation of Human Adipose-Derived Stromal Cell Osteogenic Differentiation by Insulin-Like Growth Factor-1 and Platelet-Derived Growth Factor-&agr; , 2010, Plastic and reconstructive surgery.

[5]  Deepak M. Gupta,et al.  Human Adipose-Derived Stromal Cells Respond to and Elaborate Bone Morphogenetic Protein-2 during In Vitro Osteogenic Differentiation , 2010, Plastic and reconstructive surgery.

[6]  F. Greco,et al.  Osteoinduction properties of different growth factors on cells from non-union patients: in vitro study for clinical application. , 2010, Journal of biological regulators and homeostatic agents.

[7]  H. Lei,et al.  Evaluation of the efficacy of platelet-rich plasma in delivering BMSCs into 3D porous scaffolds. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[8]  Raj D. Rao,et al.  The effect of platelet-rich plasma and bone marrow on murine posterolateral lumbar spine arthrodesis with bone morphogenetic protein. , 2009, The Journal of bone and joint surgery. American volume.

[9]  L. Tagliabue,et al.  Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients. , 2008, Injury.

[10]  Antonios G Mikos,et al.  Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. , 2008, Bone.

[11]  Vasif Hasirci,et al.  Sequential growth factor delivery from complexed microspheres for bone tissue engineering. , 2008, Biomaterials.

[12]  D. Mooney,et al.  Improved bone healing by angiogenic factor-enriched platelet-rich plasma and its synergistic enhancement by bone morphogenetic protein-2. , 2008, The International journal of oral & maxillofacial implants.

[13]  Yunsong Liu,et al.  Injectable tissue-engineered bone composed of human adipose-derived stromal cells and platelet-rich plasma. , 2008, Biomaterials.

[14]  M. Hincke,et al.  Fibrin: a versatile scaffold for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[15]  Ana Jaklenec,et al.  Sequential release of bioactive IGF-I and TGF-beta 1 from PLGA microsphere-based scaffolds. , 2008, Biomaterials.

[16]  E. Loboa,et al.  Effects of serial passaging on the adipogenic and osteogenic differentiation potential of adipose-derived human mesenchymal stem cells. , 2007, Tissue engineering.

[17]  S. Li,et al.  The effect of different platelet‐rich plasma concentrations on proliferation and differentiation of human periodontal ligament cells in vitro , 2007, Cell proliferation.

[18]  J. Jansen,et al.  Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair. , 2007, Osteoarthritis and cartilage.

[19]  R. Jung,et al.  Platelet-rich plasma and fibrin as delivery systems for recombinant human bone morphogenetic protein-2. , 2005, Clinical oral implants research.

[20]  M. Hedrick,et al.  Multipotential differentiation of adipose tissue-derived stem cells. , 2005, The Keio journal of medicine.

[21]  Antonios G Mikos,et al.  Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Eben Alsberg,et al.  Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. , 2004, Bone.

[23]  E. Freymiller.  Platelet-rich plasma: evidence to support its use. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[24]  C. Babbush,et al.  An In Vitro and In Vivo Evaluation of Autologous Platelet Concentrate in Oral Reconstruction , 2003, Implant dentistry.