PMID- 19277010 OWN - NLM STAT- MEDLINE DCOM- 20090629 LR - 20211020 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 17 IP - 5 DP - 2009 May TI - Baculovirus transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation. PG - 889-96 LID - 10.1038/mt.2009.30 [doi] AB - 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. FAU - Chuang, Ching-Kuang AU - Chuang CK AD - Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan. FAU - Wong, Tong-Hong AU - Wong TH FAU - Hwang, Shiaw-Min AU - Hwang SM FAU - Chang, Yu-Han AU - Chang YH FAU - Chen, Guan-Yu AU - Chen GY FAU - Chiu, Yung-Chung AU - Chiu YC FAU - Huang, Shiu-Feng AU - Huang SF FAU - Hu, Yu-Chen AU - Hu YC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090310 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (Interferon-alpha) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Baculoviridae/*genetics MH - Enzyme-Linked Immunosorbent Assay MH - Flow Cytometry MH - Humans MH - Immunohistochemistry MH - Interferon-alpha/metabolism MH - Interferon-gamma/metabolism MH - Interleukin-1beta/metabolism MH - Interleukin-6/metabolism MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*immunology/*virology MH - Polymerase Chain Reaction MH - Rats MH - Transduction, Genetic MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC2835125 EDAT- 2009/03/12 09:00 MHDA- 2009/06/30 09:00 PMCR- 2010/05/01 CRDT- 2009/03/12 09:00 PHST- 2009/03/12 09:00 [entrez] PHST- 2009/03/12 09:00 [pubmed] PHST- 2009/06/30 09:00 [medline] PHST- 2010/05/01 00:00 [pmc-release] AID - S1525-0016(16)31789-0 [pii] AID - 10.1038/mt.2009.30 [doi] PST - ppublish SO - Mol Ther. 2009 May;17(5):889-96. doi: 10.1038/mt.2009.30. Epub 2009 Mar 10.