Biomedical subjects

Jeffrey Pimentel

Publications and source records attributed to Jeffrey Pimentel.

4 recordsLinked to original sources

PubMed2006

Bone marrow production of lung cells: the impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype.

OBJECTIVE: Previous studies have demonstrated the production of various types of lung cells from marrow cells under diverse experimental conditions. Our aim was to identify some of the variables that influence conversion in the lung. METHODS: In separate experiments, mice received various doses of total-body irradiation followed by transplantation with whole bone marrow or various subpopulations of marrow cells (Lin(-/+), c-kit(-/+), Sca-1(-/+)) from GFP(+) (C57BL/6-TgN[ACTbEGFP]1Osb) mice. Some were given intramuscular cardiotoxin and/or mobilized with granulocyte colony-stimulating factor (G-CSF). RESULTS: The production of pulmonary epithelial cells from engrafted bone marrow was established utilizing green fluorescent protein (GFP) antibody labeling to rule out autofluorescence and deconvolution microscopy to establish the colocaliztion of GFP and cytokeratin and the absence of CD45 in lung samples after transplantation. More donor-derived lung cells (GFP(+)/CD45(-)) were seen with increasing doses of radiation (5.43% of all lung cells, 1200 cGy). In the 900-cGy group, 61.43% of GFP(+)/CD45(-) cells were also cytokeratin(+). Mobilization further increased GFP(+)/CD45(-) cells to 7.88% in radiation-injured mice. Up to 1.67% of lung cells were GFP(+)/CD45(-) in radiation-injured mice transplanted with Lin(-), c-kit(+), or Sca-1(+) marrow cells. Lin(+), c-kit(-), and Sca-1(-) subpopulations did not significantly engraft the lung. CONCLUSIONS: We have established that marrow cells are capable of producing pulmonary epithelial cells and identified radiation dose and G-CSF mobilization as variables influencing the production of lung cells from marrow cells. Furthermore, the putative lung cell-producing marrow cell has the phenotype of a hematopoietic stem cell.

Animals↗

PubMed2005

Stem cells and pulmonary metamorphosis: new concepts in repair and regeneration.

Adult stem cells are likely to have much more versatile differentiation capabilities than once believed. Numerous studies have appeared over the past decade demonstrating the ability of adult stem cells to differentiate into a variety of cells from non-hematopoietic organs, including the lung. The goal of this review is to provide an overview of the growth factors which are thought to be involved in lung development and disease, describe the cells within the lung that are believed to replace cells that have been injured, review the studies that have demonstrated the transformation of bone marrow-derived stem cells into lung cells, and describe potential clinical applications with respect to human pulmonary disease.

Animals↗

PubMedDate not supplied

Stem cell plasticity: an overview.

The capacity of adult bone marrow cells to convert to cells of other tissues, referred to by many as stem cell plasticity, was the focus of the meeting in Providence entitled "Challenges in the Era of Stem Cell Plasticity". The meeting provided a showcase for the many impressive positive results on tissue restoration including the capacity of purified marrow stem cells to restore heart, skin, and liver function in impaired mice or humans. This area of research has become a center of controversy, although it is not clear why. Calls for clonality, robustness, and function have been shown to be erroneous or premature. A call for clonality (which has been shown nicely in one study) is meaningless on a predefined stem cell population which is intrinsically heterogeneous, as they all are. Robustness means nothing; it all depends on the details of the situation. Function on an organ level is, of course, the goal of many investigators and should not be raised as a limiting consideration. Lastly, fusion has been highlighted as undermining studies with adult stem cells. It, of course, does not. Fusion is simply a means to a final goal, which occurs in certain settings of marrow conversions (transdifferentiation) and not in others. We hypothesize that the conversion phenomena may, in fact, be due to one or several marrow stem cells with broad differentiation potential which can be expressed when the cell is placed in an environment with the appropriate inductive signals. Furthermore, initial events may be relatively rare and significant conversion numbers may be obtained with massive or ongoing selection. Fusion appears in an initial mechanism in some cases and not in others. Overall, the therapeutic potential of adult marrow stem cells is very intriguing, and successful use therapeutically will probably depend on definition of the most appropriate transplant model and tissue injury.

Animals↗

PubMedDate not supplied

Homing and conversion of murine hematopoietic stem cells to lung.

The hematopoietic stem cell population, lineage negative-Sca positive (HSC), displays a homing defect into bone marrow (BM) after 48-h exposure to interleukin (IL)-3, IL-6, IL-11, and steel factor [J. Hematother. Stem Cell Res. 11 (2002) 913]. Cytokine treatment of murine marrow leads to reversible alterations in adhesion protein expression, which may explain the changes in homing. We evaluated 3 h homing to nonhematopoietic organs of marrow cells exposed to cytokines for 0, 18, 24, 40 and 48 h. HSC cells from C57BL/6J mice were cultured and labeled with the cytoplasmic fluorescent dye CFSE. We found homed events from uncultured cells in spleen, liver and lung, but no events were seen in duodenum or anterior tibialis muscle. Culture in cytokines led to decreased homing to marrow at 24 and 48 h with parallel changes in spleen homing. There was little variability of homing to liver, however the number, of homed events in lung was markedly increased when 24-h cultured cells were assessed. This was approximately a 10-fold increase compared to the 0 h time point (flow cytometry). Homing was determined by evaluation of frozen section (8 microm) by fluorescent microscopy for spleen, liver, duodenum, anterior tibialis and lung. Data were confirmed by flow cytometry from each organ including marrow. These data indicate the presence of a lung homing "hotspot" at 24 h of cytokine culture; this is a time when the stem progenitors cells are in mid S-phase. Altogether these data suggest that homing of marrow cell to nonmarrow organs may fluctuate with cell cycle transit and that there is a lung homing hotspot in mid-S.

Animals↗