Biologic effect and immunoisolating behavior of BMP-2 gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules.
We investigated the encapsulation of BMP-2 gene-modified mesenchymal stem cells (MSCs) in alginate-poly-L-lysine (APA) microcapsules for the persistent delivery of bone morphogenic protein-2 (BMP-2) to induce bone formation. An electrostatic droplet generator was employed to produce APA microcapsules containing encapsulated beta-gal or BMP-2 gene-transfected bone marrow-derived MSCs. We found that X-gal staining was still positive 28 days after encapsulation. Encapsulated BMP-2 gene-transfected cells were capable of constitutive delivery of BMP-2 proteins for at least 30 days. The encapsulated BMP-2 gene-transfected MSCs or the encapsulated non-gene transfer MSCs (control group) were cocultured with the undifferentiated MSCs. The gene products from the encapsulated BMP-2 cells could induce the undifferentiated MSCs to become osteoblasts that had higher alkaline phosphatase (ALP) activity than those in the control group (p<0.05). The APA microcapsules could inhibit the permeation of fluorescein isothiocyanate-conjuncted immunoglobulin G. Mixed lymphocyte reaction also indicates that the APA microcapsules could prevent the encapsulated BMP-2 gene-transfected MSCs from initiating the cellular immune response. These results demonstrated that the nonautologous BMP-2 gene-transfected stem cells are of potential utility for enhancement of bone repair and bone regeneration in vivo.
Ding
H F
HF
Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, PR China.
Liu
R
R
Li
B G
BG
Lou
J R
JR
Dai
K R
KR
Tang
T T
TT
D000464:Alginates / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000276:immunology*; D002214:Capsules; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry; D014162:Transfection / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
D000464:Alginates; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002214:Capsules; D016212:Transforming Growth Factor beta; C051546:alginate-polylysine-alginate; D011107:Polylysine