Engraftment of bone marrow-derived epithelial cells.

The long-held concept that transplanted bone marrow (BM)-derived cells contribute only to cells of the hematopoietic system was challenged by data from our laboratory showing that a single male BM-derived cell could not only reconstitute the hematopoietic system of an irradiated female recipient, but could also lead to the generation of mature BM-derived epithelial cells in the liver, lung, skin, and gastrointestinal tract. Careful costaining and single-cell analyses have been used to rule out false positive cells due to inadequate detection techniques in microscopy or cell overlay. Since this initial discovery, we have sought to understand the mechanisms underlying the formation of BM-derived epithelial cells, and to evaluate their therapeutic use for gene therapy and/or tissue regeneration.

Bone marrow-derived cells contribute to epithelial engraftment during wound healing.

Recent findings suggest that bone marrow-derived cells (BMDC) may contribute to tissue maintenance throughout the body. However, it is not yet known whether marrow-derived epithelial cells are capable of undergoing proliferation. Our laboratory has shown that BMDC engraft as keratinocytes in the skin at low levels ( View Article and Find Full Text PDF

Plasticity of bone marrow-derived stem cells.

Stem cell plasticity refers to the ability of adult stem cells to acquire mature phenotypes that are different from their tissue of origin. Adult bone marrow cells (BMCs) include two populations of bone marrow stem cells (BMCs): hematopoietic stem cells (HSCs), which give rise to all mature lineages of blood, and mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat. In this article, we review the literature that lends credibility to the theory that highly plastic BMCs have a role in maintenance and repair of nonhematopoietic tissue.

Lack of a fusion requirement for development of bone marrow-derived epithelia.

Analysis of developmental plasticity of bone marrow-derived cells (BMDCs) is complicated by the possibility of cell-cell fusion. Here we demonstrate that epithelial cells can develop from BMDCs without cell-cell fusion. We use the Cre/lox system together with beta-galactosidase and enhanced green fluorescent protein expression in transgenic mice to identify epithelial cells in the lung, liver, and skin that develop from BMDCs without cell fusion.

Cotransplantation of human mesenchymal stem cells enhances human myelopoiesis and megakaryocytopoiesis in NOD/SCID mice.

Objective: For approximately 5% of autologous transplant recipients and a higher proportion of allogeneic transplant recipients, low level and delayed platelet engraftment is an ongoing problem. Mesenchymal stem cells (MSC), which can be derived from bone marrow as well as other organs, are capable of differentiation into multiple cell types and also support hematopoiesis in vitro. Because cotransplantation of marrow-derived stromal cells has been shown to enhance engraftment of human hematopoietic stem cells, we hypothesized that cotransplantation of MSC could enhance platelet and myeloid cell development.

Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium.

Gene therapy application to pulmonary airways and alveolar spaces holds tremendous promise for the treatment of lung diseases. However, safe and effective long-term gene expression using viral and nonviral vectors has not yet been achieved. Adenoviral vectors, with a natural affinity for airway epithelia, have been partially effective, but are inflammatory and induce only transient gene expression.

Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow.

Objective: To better understand the process by which pneumocytes can be derived from bone marrow cells, we investigated the in vivo kinetics of such engraftment following lethal irradiation.

Methods: A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants (BMT) from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 post-BMT (n = 3 for each time point). Additionally, 2 female mice who had received 200 male fluorescence-activated cell sorter (FACS)-sorted CD34(+)lin(-) cells were sacrificed 8 months post-BMT.