Immune responses during healing of massive segmental femoral bone defects mediated by hybrid baculovirus-engineered ASCs.
Baculovirus holds promise for genetic modification of adipose-derived stem cells (ASCs) and bone engineering. To explore the immune responses during bone healing and the cell fate, ASCs were mock-transduced (Mock group), transduced with the baculovirus transiently expressing growth factors promoting osteogenesis (BMP2) or angiogenesis (VEGF) (S group), or transduced with hybrid baculoviruses persistently expressing BMP2/VEGF (L group). After allotransplantation into massive femoral defects in rabbits, these 3 groups triggered similar degrees of transient inflammatory response (e.g. neutrophil proliferation and immune cell infiltration into the graft site), revealing that baculovirus and transgene products did not exacerbate the inflammation. The cells in all 3 groups underwent apoptosis initially, persisted for at least 4 weeks and were eradicated thereafter. The L group prolonged the in vivo BMP2/VEGF expression (up to 4 weeks), extended the antibody responses, and slightly enhanced the cell-mediated cytotoxicity. Nonetheless, the L group led to remarkably better bone healing and remodeling than the Mock and S groups. These data confirmed that the ASCs engineered with the hybrid BV imparted prolonged expression of BMP2/VEGF which, although stimulated low levels of humoral and cell-mediated immune responses, essentially augmented the healing of massive segmental bone defects.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.
Chin-Yu
CY
Lin
Kun-Ju
KJ
Lin
Kuei-Chang
KC
Li
Li-Yu
LY
Sung
Swei
S
Hsueh
Chia-Hsin
CH
Lu
Guan-Yu
GY
Chen
Chiu-Ling
CL
Chen
Shiu-Feng
SF
Huang
Tzu-Chen
TC
Yen
Yu-Han
YH
Chang
Yu-Chen
YC
Hu
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis; D016367:Baculoviridae; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D016723:Bone Remodeling; D002465:Cell Movement; D003602:Cytotoxicity, Immunologic; D005269:Femur / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology*; D005818:Genetic Engineering; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D011817:Rabbits; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D019076:Transgenes / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology*
D000906:Antibodies; D055396:Bone Morphogenetic Protein 2; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma