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Updated: Sep 20, 2026
Cell-cell Fusion of Genome Edited Cell Lines for Perturbation of Cellular Structure and Function
Published on: December 7, 2019
Little evidence for cell fusion between recipient and donor-derived cells
Akio Saiura1, Masataka Sata, Miwa Washida
1Department of Surgery, University of Tokyo, Graduate School of Medicine, Tokyo 113-8655, Japan.
Insights
Recipient bone marrow cells, not donor cells, form the neointima in cardiac transplants. This finding clarifies the cellular origins of transplant-associated atherosclerosis, a key factor in long-term graft survival.
Area of Science:
- Immunology
- Cardiovascular Biology
- Transplantation Science
Background:
- Accelerated coronary atherosclerosis, or graft vasculopathy, significantly impacts long-term survival in cardiac transplant recipients.
- The precise cellular origins and mechanisms driving transplant-associated atherosclerosis are not fully understood.
Purpose of the Study:
- To investigate the cellular source of vascular cells contributing to neointimal hyperplasia in cardiac allografts.
- To differentiate between donor-derived and recipient-derived cells within the developing graft vasculopathy.
Main Methods:
- Heterotopic heart transplantation was performed in genetically modified mice (ubiquitous LacZ or green fluorescent protein [GFP] expression).
- Chimeric mice with bone marrow cells from LacZ or GFP donors were used to track cell origins.
- Immunohistochemistry was employed to identify cell markers and donor/recipient origin.
Main Results:
- Neointimal hyperplasia was observed in graft coronary arteries 4 weeks post-transplantation, expressing smooth muscle cell markers.
- The majority of neointimal cells originated from the recipient, not the donor graft medial smooth muscle cells.
- In chimeric mice, bone marrow-derived cells constituted most of the neointimal cells, indicating their significant contribution.
Conclusions:
- Recipient bone marrow-derived cells are a primary source for the neointima in transplant-associated atherosclerosis.
- Spontaneous cell fusion between recipient and donor cells appears to be a rare event in this process.
- Understanding these cellular origins can inform strategies to prevent graft vasculopathy.
Abstract:
Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of the transplant-associated atherosclerosis remains largely unknown. Here, we investigated the origin of the vascular cells that contribute to graft vasculopathy. We performed heterotopic heart transplantation using genetically modified mice that express LacZ or green fluorescent protein (GFP) ubiquitously and constitutively. At 4 weeks after transplantation, the graft coronary arteries developed neointimal hyperplasia, expressing several smooth muscle cell markers. Most of the neointimal cells were composed of recipient cells but not graft medial smooth muscle cells. We seldom detected neointimal cells that were positive for both LacZ and GFP. When we transplanted wild-type cardiac allografts into the chimeric mice whose bone marrow cells had been replaced with those of LacZ-mice or GFP-mice, we observed that most of the neointimal cells were derived from the bone marrow. These findings suggest that recipient bone marrow-derived cells contribute to the pathogenesis of graft arteriosclerosis. Spontaneous cell fusion between recipient and donor-derived cells seems to be a rare event, if it occurs at all.
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