Showing papers by "Diane S. Krause published in 2005"

POSITION PAPER Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement

Abstract: The plastic-adherent cells isolated from BM and other sources have come to be widely known as mesenchymal stem cells (MSC). However, the recognized biologic properties of the unfractionated population of cells do not seem to meet generally accepted criteria for stem cell activity, rendering the name scientifically inaccurate and potentially misleading to the lay public. Nonetheless, a bona fide MSC most certainly exists. To address this inconsistency between nomenclature and biologic properties, and to clarify the terminology, we suggest that the fibroblast-like plastic-adherent cells, regardless of the tissue from which they are isolated, be termed multipotent mesenchymal stromal cells, while the term mesenchymal stem cells is used only for cells that meet specified stem cell criteria. The widely recognized acronym, MSC, may be used for both cell populations, as is the current practice; thus, investigators must clearly define the more scientifically correct designation in their reports. The International Society for Cellular Therapy (ISCT) encourages the scientific community to adopt this uniform nomenclature in all written and oral communications.

Bone marrow plasticity revisited: protection or differentiation in the kidney tubule?

Abstract: Epithelial organs such as the intestine and skin have a relatively high rate of cell loss and thus require a reservoir of stem cells capable of both replacing the lost epithelia and maintaining the reservoir. Whether the kidney has such a stem cell niche has been a subject of great interest; the majority of data suggest that replacement of renal epithelial cells occurs via dedifferentiation and proliferation of existing tubular cells, while some studies demonstrate the presence of potential tubular stem cells in the renal interstitium. However, recent reports have suggested that the bone marrow may also be a source of stem cells for tubule turnover and/or repair. In this issue of the JCI, 2 groups explore the role of endogenous cells versus bone marrow–derived cells in mediating tubule repair. Duffield and colleagues demonstrate that bone marrow does contain cells capable of protecting the kidney from ischemic injury, but found that these cells do not act by direct incorporation into the repaired tubular segments. In contrast, Lin and coworkers found that some bone marrow–derived cells do appear to incorporate into the injured tubule as epithelial cells (see the related article beginning on page 1756). Importantly, both groups conclude that the majority of tubule repair occurs via proliferation of endogenous renal cells rather than incorporation of bone marrow–derived cells.

Engraftment of bone marrow-derived epithelial cells.

Abstract: 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. Several reports have shown that donor BM-derived cells, possibly macrophages, can fuse with existing host epithelial cells to form heterokaryons that express both donor and tissue-specific markers. While this is certainly true for murine tyrosinemia models, we have used a Cre-lox system to demonstrate that fusion is not a requirement for the generation of BM-derived epithelial cells and is likely not responsible for the BM-derived epithelial cells generated after standard BM transplantation. In a proof of principal experiment for potential gene therapy applications, we have shown that autologous BM-derived cells transfected with a transgene prior to BM transplantation are able to develop into mature type-II pneumocytes that express the trans-gene. We also discuss future research directions in the field and the therapeutic potential of BM-derived epithelia, including ongoing work to test whether combined cell and gene therapy can be used therapeutically in preclinical mouse models of human disease.

Engraftment of Bone Marrow‐Derived Epithelial Cells

Abstract: Discoveries of the ability of bone marrow-derived cells (BMDCs) to differentiate into nonhematopoietic cells have opened up a new field of inquiry in adult stem cell plasticity. There are far more questions than there are answers to date. We and others have investigated whether differentiation occurs in response to tissue damage, what the underlying mechanisms might be, and whether this plasticity may be useful clinically. BMDC have been shown to differentiate into mature-appearing epithelial cells in the lung, liver, gastrointestinal tract, skin, buccal mucosa, and kidney. The mechanism(s) by which cells transition to these nonhematopoietic phenotypes is not yet clear, but possibilities include cell-to-cell fusion, direct differentiation of a nonhematopoietic precursor cell from the BM, and transdifferentiation of a BM cell that had previously been committed to a different phenotype. Data obtained to date support the first two possibilities, and there are no data proving that transdifferentiation is responsible for the engraftment of marrow-derived epithelial cells. Theoretically, the engraftment of marrow-derived cells as nonhematopoietic cell types could be used in either the autologous or the allogeneic setting to restore functional epithelial cells to a diseased organ. For example, a marrow-derived cell that has been transduced to express a specific transgene can continue to express this transgene after it engrafts as a nonhematopoietic epithelial cell in the lung. Analyses of the kinetics of this engraftment suggest that it can be increased within days to weeks following certain types of injury, depending on the tissue examined. Most reports of adult stem cell plasticity show relatively low frequencies of marrow-derived nonhematopoietic cells, on the order of 1 in 10(3) to 1 in 10(4) epithelial cells in many organs being marrow derived. This frequency is likely to be too low to be of therapeutic relevance. Therefore, future efforts will need to be focused on enhancing levels of engraftment.