Baculovirus transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.
Baculovirus holds great promise for the genetic modification of mesenchymal stem cells (MSCs). However, whether baculovirus transduction provokes undesired MSCs responses that might compromise their in vivo applications has yet to be examined. Hereby, we unraveled that baculovirus transduction of human MSCs upregulated the transcription of interleukin (IL)-1beta, interferon (IFN)-alpha and IL-6, but not tumor necrosis factor (TNF)-alpha and IFN-gamma. However, only IL-6 secretion was detectable by enzyme-linked immunosorbent assay (ELISA). Baculovirus transduction also stimulated transient, low level upregulation of human leukocyte antigen I (HLA-I) on the human MSCs surface, yet it did not either altered the HLA-II expression or impaired the MSCs ability to inhibit lymphocyte proliferation. After transplantation into allogeneic rats, the transduced rat MSCs elicited transient, mild macrophage responses, but the cells remained tolerant as judged by the persistence of transplanted cells and absence of CD8(+) T cells infiltration. Besides, transplantation of the transduced MSCs did not provoke systemic induction of monocytes and CD8(+) T cells. This study, for the first time, explores the responses of MSCs to virus transduction and confirms the safety of transplanting baculovirus-engineered MSCs into immunocompetent animals for cell-based gene therapy.
Chuang
Ching-Kuang
CK
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Wong
Tong-Hong
TH
Hwang
Shiaw-Min
SM
Chang
Yu-Han
YH
Chen
Guan-Yu
GY
Chiu
Yung-Chung
YC
Huang
Shiu-Feng
SF
Hu
Yu-Chen
YC
D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000821:virology*; D016133:Polymerase Chain Reaction; D051381:Rats; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma