ArticlesDifferentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study
Introduction
Evidence from studies in recipients of bone-marrow transplants shows that bone marrow-derived (BMD) cells can differentiate into cells other than blood. This occurrence is of importance because such cells could be used to regenerate organs after disease or trauma.1, 2, 3, 4, 5 However, the plasticity of BMD cells has been questioned by results of studies suggesting that stem cells might fuse with other cells and give the appearance of differentiation.6, 7 Furthermore, caution is needed in interpretation of data purporting to show that non-haemopoietic cells are derived from donor BMD cells.8, 9, 10 Tissues, especially when affected by graft-versus-host disease (GVHD), might contain infiltrating donor haemopoietic or lymphoid cells. In histological sections, non-haemopoietic tissue cells might be confounded with haemopoietic cells because of cell overlap (attributable to the thickness of the sections) or loss of haemopoietic lineage-specific markers.
We aimed to establish whether BMD cells differentiate into cells of another tissue lineage, and to assess whether this event is attributable to fusion. To avoid contamination of our samples by haemopoietic inflammatory cells, we did our studies on healthy transplant recipients without oral GVHD, several years after bone-marrow transplantation.
Section snippets
Patients
Bone-marrow stem-cell transplant recipients residing within the USA, who each had received an allogeneic transplant from a male sibling donor through protocols from the National Heart, Lung, and Blood Institute, were invited to participate in the study. All those who agreed to participate were well, in haematological remission, with full donor lymphohaemopoietic engraftment and no active oral GVHD. The transplants these patients had received consisted of at least 3·106 CD34+ cells/kg and a
Results
Five females, 4–6 years after receiving a transplant from an HLA-identical brother for leukaemia, agreed to participate (table 1). Recipients 1, 2, 3, and 5 underwent a myeloablative conditioning regimen consisting of 4 days of total body irradiation (13·6 Gy) and 2 days of cyclophosphamide 60 mg/kg. Recipient 4 received the same dose of cyclophosphamide plus fludarabine 125 mg/m2 over 5 days. GVHD developed in four: acute grade 1 in recipient 1; chronic liver GVHD in recipient 3; extensive
Discussion
These results indicate that cells derived from marrow or granulocyte-colony stimulating factor mobilised blood cells migrate into the cheek and differentiate into epithelial cells. These results might therefore represent transdifferentiation of haemopoietic or stromal stem cells, or transplantation of a hypothetical epithelial progenitor cell.
Four criteria have been proposed to show plasticity of adult stem cells.14, 15 The first criterion states that cells grafted should be clonal. Our study
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2016, Transplant ImmunologyCitation Excerpt :Our data shows that from 1 to 48 h after transplantation, the quantity of donor origin cells gradually decreases in the affected foot and then remains at the same level up to 72 h. Following 48 h after transplantation, a 100-fold decrease (from 1:100 to 1:10,000) of the donor type cells in foot edema was observed; however it remained more than 10 times higher than that of the healthy foot. According to the data in literature, donor HSC after allogeneic transplantation can be found almost in all organs and tissues of the recipient [2–4,6]. The donor origin cells were not detected only in the recipient's hair follicle [7].