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Baculovirus transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.

ABSTRACT: 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.

SUBMITTER: Chuang CK

PROVIDER: S-EPMC2835125 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Baculovirus transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.

Chuang Ching-Kuang CK 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

Molecular therapy : the journal of the American Society of Gene Therapy 20090310 5

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 ...[more]

PMID: 19277010

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Project description:Functional activation of stem cells after transplantation is a main concern in stem cell therapy. For local transplantation, mesenchymal stem cells (MSCs) are usually administered via scaffolds, either by direct implantation or after preculturing of cells, and it is unclear which is better for the activation of transplanted cells. In this study, we investigated the in vivo gene expression activity of human MSCs (hMSCs) transplanted into calvarial defects either directly post-seeding on collagen sponges (Group 1) or after overnight in vitro culturing post-seeding (Group 2). Real-time reverse transcription-polymerase chain reaction at days 7 and 14 after transplantation identified a time-dependent, rapid decrease in gene expression by the hMSCs, which in Group 1 was slightly more attenuated than in Group 2. Both groups exhibited a limited range of human-specific gene expression, which involved type I collagen (ColI), fibronectin, stromal cell-derived factor (SDF-1), and osteoprotegerin. Among these, ColI expression was the most efficient, with higher levels in Group 1 than Group 2. There was a lack of evidence for the expression of osteoblast differentiation-related markers or trophic factors, while resident cells showed clear expression of those genes. Rat-specific β-actin expression in Group 2 was least among the scaffold control, Group 1, and Group 2, and this pattern was repeated in the expression of other rat osteogenic genes. Group 1 transplants positively influenced the osteogenic process of the defect tissue in part, and rat IGF-1 expression was significantly increased in Group 1. This tendency of gene expression by hMSCs in a rat model was very similar to what was observed in transplantations using immunodeficient mice. The current study showed that a main gene expressed by transplanted hMSCs during the initial weeks following transplantation is ColI, with a lack of differentiation-related markers or growth factor expression by hMSCs. Our data suggest that direct transplantation of hMSCs loaded on a collagen sponge is more efficient for gene activation in transplanted hMSCs, and more favorable to the local host tissue than transplantation after preculturing of cells.

Dataset Information

Baculovirus transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.

Publications

Baculovirus transduction of mesenchymal stem cells: in vitro responses and in vivo immune responses after cell transplantation.

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