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PubMed2006

Stem phototropism of trees: a possible significant factor in determining stem inclination on forest slopes.

BACKGROUND AND AIMS: The main stems of trees on forest slopes incline down the slope to various extents that are characteristic of the species. The inclination has been explained as an active response to a horizontally asymmetrical light environment, but the contributing physiological mechanisms are unknown. The present study tested the hypothesis that stem phototropism, gravitropism, or a combination of the two determines the inclination of tree stems on forest slopes. METHODS: Cryptomeria japonica, Pinus densiflora, Quercus myrsinaefolia and Q. serrata were studied. Measurements were made of stem inclination of mature trees on forest slopes in uniform plantations of each species, and changes in stem inclination of potted seedlings in response to illumination treatments (unilateral or overhead) and inclination treatments (artificially inclined or erect). Indices of phototropic and gravitropic responsiveness were evaluated for each species, calculated from the change in stem inclination in response to artificial inclination with unilateral or overhead illumination. KEY RESULTS: Stem inclination on forest slopes varied significantly among species: Q. serrata inclined most in the down-slope direction, C. japonica inclined the least, and P. densiflora and Q. myrsinaefolia were intermediate. The change in stem inclination of seedlings in each treatment varied significantly among species. One-year-old stems of Q. serrata and 2-year-old stems of Q. myrsinaefolia bent toward the light source. Interspecific variation in the change in stem inclination in response to the unilateral illumination or that in the index of phototropic responsiveness was strongly correlated with the variation in stem inclination on forest slopes. CONCLUSIONS: The orientation of woody stems that have finished elongation can be actively controlled by phototropism. Interspecific variation in phototropic responsiveness of trees is a possible significant determinant of interspecific variation in stem inclination on forest slopes.

Geography↗
PubMed2005

Adult stem cells and cancer stem cells: tie in or tear apart?

Stem cell research is one of the new frontiers of medical science. Because of the unique self-renewable ability and powerful potential to differentiate, stem cells can be viewed as the mother of all cells in the body and have been investigated as a possible tool for reversing the degeneration and damage on organs. Recently, successful isolating cancerous stem cells from leukemia, breast and brain cancers provide a new target for eliminate cancer; however, it hints an increasing caution in using adult stem cells for organ repair. Cancerous stem cells share the same properties of self-renewal and differentiation with normal stem cells, with the addition of similar phenotype of adult stem cells isolated from the same tissue. Some believe that cancerous stem cells are derived from mutation of the normal stem cells, whereas others suspect it to be from different origins. Further investigation of the intrinsic factor underlying the behavior of adult stem cells and cancerous stem cells will shed light on both the fields of tissue engineering and cancer therapy. In this review, recent progresses in the studies of adult stem cells and cancerous stem cells are summarized to facilitate a better understanding and elicit much attention in this field.

Animals↗
PubMed2000

Temperature variation and distribution of living cells within tree stems: implications for stem respiration modeling and scale-up.

Few studies have examined variation in respiration rates within trees, and even fewer studies have focused on variation caused by within-stem temperature differences. In this study, stem temperatures at 40 positions in the stem of one 30-year-old Norway spruce (Picea abies (L.) Karst.) were measured during 40 days between July 1994 and June 1995. The temperature data were used to simulate variations in respiration rate within the stem. The simulations assumed that the temperature-respiration relationship was constant (Q10 = 2) for all days and all stem positions. Total respiration for the whole stem was calculated by interpolating the temperature between the thermocouples and integrating the respiration rates in three dimensions. Total respiration rate of the stem was then compared to respiration rate scaled up from horizontal planes at the thermocouple heights (40, 140, 240 and 340 cm) on a surface area and on a sapwood volume basis. Simulations were made for three distributions of living cells in the stems: one with a constant 5% fraction of living cells, disregarding depth into the stem; one with a living cell fraction decreasing linearly with depth into the stem; and one with an exponentially decreasing fraction of living cells. Mean temperature variation within the stem was 3.7 degrees C, and was more than 10 degrees C for 8% of the time. The maximum measured temperature difference was 21.5 degrees C. The corresponding mean variation in respiration was 35% and was more than 50% for 24% of the time. Scaling up respiration rates from different heights between 40 and 240 cm to the whole stem produced an error of 2 to 58% for the whole year. For a single sunny day, the error was between 2 and 72%. Thus, within-stem variations in temperature may significantly affect the accuracy of scaling respiration data obtained from small samples to whole trees. A careful choice of chamber position and basis for scaling is necessary to minimize errors from variation in temperature.

Body Temperature↗
PubMed2003

Differences in heat sensitivity between normal and acute myeloid leukemic stem cells: feasibility of hyperthermic purging of leukemic cells from autologous stem cell grafts.

OBJECTIVES: In autologous stem cell transplantation contamination of the graft with malignant cells is frequently noticed and necessitates the use of in vivo or in vitro purging modalities. The hematopoietic recovery after transplantation depends on the number of stem and progenitor cells in the transplant. Therefore, in the present study the effects of hyperthermic treatment on the human normal and acute myeloid leukemic (AML) stem cell compartment were investigated. METHODS: Normal bone marrow and AML blasts were heat treated up to 120 minutes at 43 degrees C. The surviving fractions of the different stem cell subsets were determined using in vitro methylcellulose and cobblestone area-forming cell (CAFC) clonogenic assays, as well as the in vivo NOD/SCID repopulating assay. The leukemic nature of the colonies from AML cells was confirmed by RT-PCR analysis. In order to increase the therapeutic index of the hyperthermic purging modality, the heat treatment was preceded by a 3-hour incubation at 37 degrees C with the ether lipid ET-18-OCH(3) (25 microg/mL). RESULTS: It could be demonstrated that normal progenitor cells are far more resistant to hyperthermia than leukemic progenitor cells (56%+/-7% vs 9.9%+/-2.6% survival after 60 minutes at 43 degrees C, respectively). Furthermore, normal hematopoietic stem cells appear to be extremely resistant to the heat treatment (94%+/-9% survival after 60 minutes at 43 degrees C). In contrast, in the leukemic stem cell compartment no significant differences in heat sensitivity between the stem cells and progenitor subsets could be observed (12.3%+/-2.9% vs 9.9%+/-2.6% survival after 60 minutes at 43 degrees C, respectively). The combined treatment resulted in a survival for normal progenitor and stem cells of 32%+/-6% and 85%+/-15% after 60 minutes at 43 degrees C, respectively. Under these conditions the number of leukemic stem cells was reduced to 1%+/-0.3%. After 120 minutes at 43 degrees C, no AML-colonies could be detected anymore. CONCLUSIONS: Our data demonstrate that leukemic stem cells have an increased hyperthermic sensitivity compared to their normal counterparts and that this difference can be further increased in combination with ET-18-OCH(3). These striking differences in heat sensitivity warrant the use of hyperthermia as a clinically applicable purging modality in autologous stem cell transplantation.

Animals↗
PubMed1999

Fluorescence-based selection of gene-corrected hematopoietic stem and progenitor cells from acid sphingomyelinase-deficient mice: implications for Niemann-Pick disease gene therapy and the development of improved stem cell gene transfer procedures.

The general utility of a novel, fluorescence-based procedure for assessing gene transfer and expression has been demonstrated using hematopoietic stem and progenitor cells. Lineage-depleted hematopoietic cells were isolated from the bone marrow or fetal livers of acid sphingomyelinase-deficient mice, and retrovirally transduced with amphotropic or ecotropic vectors encoding a normal acid sphingomyelinase (ASM) cDNA. Anti-c-Kit antibodies were then used to label stem- and progenitor-enriched cell populations, and the Bodipy fluorescence was analyzed in each group after incubation with a Bodipy-conjugated sphingomyelin. Only cells expressing the functional ASM (ie, transduced) could degrade the sphingomyelin, thereby reducing their Bodipy fluorescence as compared with nontransduced cells. The usefulness of this procedure for the in vitro assessment of gene transfer into hematopoietic stem cells was evaluated, as well as its ability to provide an enrichment of transduced stem cells in vivo. To show the value of this method for in vitro analysis, the effects of retroviral transduction using ecotropic versus amphotropic vectors, various growth factor combinations, and adult bone marrow versus fetal liver stem cells were assessed. The results of these studies confirmed the fact that ecotropic vectors were much more efficient at transducing murine stem cells than amphotropic vectors, and that among the three most commonly used growth factors (stem cell factor [SCF] and interleukins 3 and 6 [IL-3 and IL-6]), SCF had the most significant effect on the transduction of stem cells, whereas IL-6 had the most significant effect on progenitor cells. In addition, it was determined that fetal liver stem cells were only approximately twofold more "transducible" than stem cells from adult bone marrow. Transplantation of Bodipy-selected bone marrow cells into lethally irradiated mice showed that the number of spleen colony-forming units that were positive for the retroviral vector (as determined by polymerase chain reaction) was 76%, as compared with 32% in animals that were transplanted with cells that were nonselected. The methods described within this manuscript are particularly useful for evaluating hematopoietic stem cell gene transfer in vivo because the marker gene used in the procedure (ASM) encodes a naturally occurring mammalian enzyme that has no known adverse effects, and the fluorescent compound used for selection (Bodipy sphingomyelin) is removed from the cells before transplantation.

Animals↗
PubMed1995

Distal stem design and the torsional stability of cementless femoral stems.

In cementless hip arthroplasty, the fit between the implant and the endosteal cavity is a critical determinant of implant stability. Although cementless implants may be stabilized through proximal fit within the metaphysis, many surgeons rely on diaphyseal fixation to provide the necessary resistance to rotational forces, especially in revision hip arthroplasty. The cross-sectional design of the femoral stem at the level of the femoral isthmus was investigated with respect to its effect on the rotational stability of the bone-stem interface. Four cross-sectional designs--a fluted stem, a finned stem, a porous-coated stem, and a slotted fluted stem--were implanted in 12 cadaveric femurs and loaded in torsion. A knurled stem, cemented into each specimen at the conclusion of testing, acted as a control stem. The torque required to cause 100 microns of displacement at the bone stem-interface ranged from 13.7 +/- 0.8 N-m with the porous-coated design to 30.1 +/- 3.7 N-m with the fluted design (P < .0001). Intermediate values of 19.5 +/- 1.4 and 19.9 +/- 2.3 N-m were observed with the finned and slotted fluted designs, respectively. In all of the cemented control stems, failure occurred at the bone-cement interface at an average torque of 34.0 +/- 3.0 N-m. Statistical analysis demonstrated that the porous-coated, finned, and slotted fluted designs were all significantly weaker in torsion than the cemented control stem; however, there was no significant difference between the torsional resistance of the solid fluted (unslotted) and cemented stems.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗
PubMed1999

Effect of flexibility of the femoral stem on bone-remodeling and fixation of the stem in a canine total hip arthroplasty model without cement.

The purpose of this study was to compare, with regard to fixation of the implant and femoral bone resorption, two fully porous-coated stems of different stiffnesses in a canine total hip arthroplasty model. A bilateral arthroplasty was carried out with insertion of a titanium-alloy stem (which had stiffness properties comparable with those of the canine femur) on one side and with insertion of a composite stem (which was three to fivefold more flexible than the canine femur) on the contralateral side. Eight femora were evaluated at six months and eight, at eighteen months after the operation, to determine the extent of bone ingrowth, periprosthetic cortical area, intracortical porosity, and bone-remodeling. Despite the markedly greater flexibility of the composite stems, no significant difference could be detected (with the numbers available), with regard to the overall degree of femoral stress-shielding, cortical area, or cortical porosity, between these stems and the stiffer, titanium-alloy stems at either time-period. However, the composite stems had less bone ingrowth and more formation of radiopaque lines than did the titanium-alloy stems. At eighteen months, the values for bone ingrowth were 9.7 +/- 5.38 percent (mean and standard deviation) for the composite stems compared with 28.1 +/- 5.31 percent for the titanium-alloy stems (p = 0.003). Furthermore, the histological sections from the femora containing a composite stem showed radiopaque lines indicative of fibrous ingrowth approximately threefold more often than did those from the femora containing a titanium-alloy stem (p = 0.02).

Alloys↗
PubMedDate not supplied

Stemness, fusion and renewal of hematopoietic and embryonic stem cells.

Development of replacement cell therapies awaits the identification of factors that regulate nuclear reprogramming and the mechanisms that control stem cell renewal and differentiation. Once such factors and signals will begin to be elucidated, new technologies will have to be envisaged where uniform differentiation of adult or embryonic stem cells along one differentiation pathway can be induced. Controlled differentiation of stem cells will require the engineering of niches and extracellular signal combinations that would amplify a particular signaling network and allow uniform and selective differentiation. Three recent advances in stem cell research open the possibility to approach engineering studies for cell replacement therapies. Fusion events between stem cells and adult cells or between adult and embryonic stem cells have been shown to result in altered fates and nuclear reprogramming of cell hybrids. Hematopoietic stem cells were shown to require Wnt signaling in order to renew. The purification of Wnt proteins would allow their use as exogenous purified cytokines in attempts to amplify stem cells before bone marrow transplantation. The homeodomain protein Nanog has been shown to be crucial for the embryonic stem cell renewal and pluripotency. However, the cardinal question of how stemness is preserved in the early embryo and adult stem cells remains opened.

Animals↗
PubMed2005

Stem cell plasticity and issues of stem cell therapy.

Today, there is much evidence suggesting that organ-specific stem cells need not rely completely on their own sources for maintenance and regeneration of an organism. In certain circumstances, mostly related to tissue damage, stem cell populations residing past the affected organ can contribute to its recovery--that means from different cell lines and also in tissues from another germ layer. The key factor in formation of self-renewing cellular clones is the presence of stem cells either from the tissue of origin or stem cells migrating from other areas and their successful settlement in an empty niche of the damaged tissue. Stem cell plasticity is the ability of adult tissue-specific stem cells to switch to new identities. The term plasticity also means stem cell phenotypic potential, which is broader than phenotypes of differentiated cells in their original tissues. Many laboratories have given evidence on stem cell plasticity; however, the presented results met with many objections from others. In the first part of our report we wish to refer to several issues associated with stem cell plasticity, transdifferentiation and fusion. Recent experimental results show that stem cells will play a key role in cell therapy. But there are still many questions to answer for scientists engaged in stem cell research. Is it possible to induce cells from one type of tissue to look and act as cells of another tissue? Do these changes occur naturally? Could plasticity be used in the treatment of fatal diseases? Cell therapy is one of the methods to treat damaged myocardial tissue. However, recent results with autologous bone marrow cells in the treatment of damaged myocardium show that this method has still many unanswered questions concerning cells, cytokines, microenvironment and other factors responsible for reparation. To date, there are many opinions either recommending or denying this method in different modifications. One question has not yet been definitely solved: What are the conditions for us to accept this method--its safety and efficacy? The future will show whether these our hopes and expectations will be fulfiled. Many experiments are needed before at least some of these questions may be answered and cell therapy become an important method for the benefit of our patients.

Cell Differentiation↗
PubMed1999

Stem cell function and engraftment is not affected by "in vivo purging" with rituximab for autologous stem cell treatment for patients with low-grade non-Hodgkin's lymphoma.

The chimeric anti-CD20 monoclonal antibody rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) has recently been approved by the US Food and Drug Administration as single-agent treatment of relapsed/refractory low-grade or follicular non-Hodgkin's lymphoma. Initial results from the pivotal clinical trial revealed that response rates to rituximab were higher in patients who previously had high-dose therapy and autologous stem cell transplantation. We have initiated a clinical trial that combines the use of rituximab with high-dose chemotherapy followed by autologous stem cell transplantation for patients with chemosensitive relapsed follicular small cleaved or mantle cell lymphoma. A unique feature of this study is that in addition to eight maintenance infusions of rituximab after autologous stem cell transplantation, patients also received rituximab 375 mg/m2 2 days before a granulocyte colony-stimulating factor-mobilized stem cell collection as "in vivo purge." We report on preliminary results demonstrating the safety and efficacy of the in vivo purge on 10 patients undergoing stem cell mobilization, nine of whom have already undergone transplantation. The peripheral blood CD34+ counts were 14.92 and 20 x 10(6)/L on day 4 and day 5, respectively, of the stem cell mobilization with granulocyte colony-stimulating factor. This compares with 11.7 and 11.8 x 10(6)/L, respectively, for the control population. The median CD34 stem cell yield in the graft collection was 3.7 x 10(6)/kg in patients receiving rituximab in vivo purge compared with 3.1 x 10(6)/kg in the control population. The target stem cell collection was successfully collected in six of 10 patients in a 1-day single large-volume leukapheresis collection, while two patients required 2 days and the last two patients required 3 days. Functional assays revealed the stem cell colony-forming unit-granulocyte monocyte and burst-forming unit-erythrocyte to be 55 and 44 colonies per plate, respectively, for the patients receiving the in vivo rituximab purge. This compares favorably with 37 and 38.5 colonies per plate, respectively, for the control population. Neutrophil engraftment took a median of 11 days for both cohorts; platelet independence was achieved in 8 days compared with 10 days for the control population. The median number of platelet transfusions was two for patients receiving rituximab and 2.5 for the control group. Assessment of serum cytokines immediately before the rituximab infusion during the stem cell mobilization and immediately after revealed a twofold to sevenfold increase in interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6. The polymerase chain reaction analysis for minimal residual disease in stem cell collections and in peripheral blood and bone marrow samples of these patients will help to determine the efficacy of rituximab in vivo purge on disease progression.

Adult↗
PubMed2005

Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+-purified stem cells.

OBJECTIVE: For recipients of haploidentically mismatched stem cell allografts, T-cell depletion is mandatory to prevent lethal graft-vs-host disease (GVHD). Prevention of GVHD can be accomplished by negative selection of T cells or positive selection of stem cells. Recently, a new method for positive selection of stem cells was introduced using monoclonal antibodies against CD133 antigen. We report five cases of successful application of immunomagnetic separation of CD133+ stem cells for haploidentically mismatched allogeneic stem cell transplantation. METHODS: Five patients with high-risk hematological malignancies, ages 7 to 63 years old (median, 17 years), underwent peripheral blood stem cell transplantation from haploidentically mismatched related donors. Conditioning protocol was tailored according to patient clinical situation and included combination of treosulfan/fludarabine/thiotepa/melphalan/Mabcampath. Two patients did not get thiotepa. One of them received a protocol that included infusion of 4.4 x 10(7) blood mononuclear cells from the donor (day -9), followed by a combination of fludarabine/cyclophosphamide/busulfex/MabCampath. Separation of CD133+ stem cells was done using CliniMACS with Miltenyi's CD133 reagent. RESULTS: The procedure was well tolerated by all patients. Early 3-lineage engraftment was documented and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophils count above 0.5 x 10(9)/L and 1.0 x 10(9)/L was 10 to 15 days (median, 14) and 11 to 29 days (median, 15), respectively. Time for platelet recovery to values greater than 20 x 10(9)/L and greater than 50 x 10(9)/L ranged from 12 to 25 days (median, 13.5), and from 14 to 34 days (median, 16), respectively. Transplant-related mortality did not occur in any of the patients. CONCLUSION: Our successful pilot trial suggests that positive selection of CD133+ stem cells may be a useful method for safe transplantation with haploidentically mismatched stem cell allografts while avoiding lethal acute and chronic GVHD. Future studies will be required to assess the clinical benefits of stem cell purification with CD133+ in comparison with CD34+ stem cells.

AC133 Antigen↗
PubMed2004

Stem cells today: B1. Bone marrow stem cells.

This review is the second in a series of four devoted to the analysis of recent studies on stem cells. The first considered embryo stem cells (ES). This review covers bone marrow stem cells. They are analysed initially in a historical perspective, and then in relation to foundation studies in the later 20th century before a detailed analysis is presented on very recent studies. Methods of identifying, culturing, expanding and grafting stem cells are described, including the separation of haemopoietic and mesenchyme cell lines (HSC and MSC) and recent more detailed analyses using numerous CD and other markers to identify very small subsets of stem cells such as multipotent adult progenitor cells (MAPC) and bone marrow stromal stem cells (BMSSC) from MSC. Queries arising on the immense potential of these stem cell lines due to the discovery of epigentic factors and cell fusions influencing their development and potency are described. A section on cord blood stem cells is followed by a detailed discussion on the modern situation regarding the clinical use of stem cells, its recent setbacks due to epigenetic factors, different approaches to the discovery of a highly multipotent bone marrow stem cell, and a brief description of embryological approaches to identifying the basic bone marrow stem cell in very early mammalian embryos.

Bone Marrow Cells↗
PubMed1999

Impact of stem cell dose on hematopoietic recovery in autologous blood stem cell recipients.

Hematopoietic recovery rates following high-dose chemotherapy in autologous blood stem cell recipients have been shown, in part, to be dependent on the source and quantity of hematopoietic stem cells infused. Mobilized blood stem cell quantity (identified by the surface expression of the CD34 antigen) has been demonstrated in multiple studies to be the strongest predictor of days to hematopoietic recovery (ie platelets and neutrophils) in autologous blood stem cell recipients. Additionally, data from four large studies confirm that prompt and sustained hematopoietic recovery will occur in the majority of patients treated with high-dose chemotherapy if a stem cell dose > or = 5 x 10(6)/kg is administered. However, multiple aphereses are needed in the majority of patients to achieve these optimal stem cell doses. Problems associated with multiple aphereses procedures include hypocalcemia, anemia, thrombocytopenia, infection, thrombosis, increased costs, and malignant cell contamination of the apheresis product. Recent data indicate that less differentiated (eg CD33 ) stem and progenitor cells result in both early and sustained hematopoietic recovery in bone marrow and blood stem cell recipients. Future trials using new growth factors such as stem cell factor (which has been shown to increase CD34+/CD33 cell mobilization), as well as improvements in purging strategies are needed to ensure prompt, sustained, and malignant-cell-free engraftment for the majority of autologous blood stem cell recipients.

Antigens, CD34↗
PubMed2001

A randomized phase II study of amifostine used as stem cell protectant in non-hodgkin lymphoma patients receiving cisplatin-based salvage chemotherapy prior to stem cell transplant.

Stem cell mobilization may be inadequate in many lymphoma patients in need for autologous stem cell transplant (SCT). In this study, we sought to evaluate a potential role of amifostine as a stem cell chemoprotective agent in lymphoma patients receiving DHAP chemotherapy in preparation for high-dose chemotherapy (HDC) and stem cell transplant (SCT). In the beginning of the DHAP course, patients were randomized 1:1 to receive amifostine at 740 mg/m(2). Stem cells were mobilized with GCSF after the last cycle of DHAP. Stem cell collection started upon ANC recovery over 1000/mm(3). Standard 10 lt. apheresis daily with a goal of a minimum of 2 x 10(6) stem cells/kg were performed. Twenty-one patients have been enrolled; 10 received amifostine pretreatment (age, 20-64) and 11 were randomized to the control arm (age, 18-63). Prior chemotherapy was balanced in the two groups. The median number of DHAP treatments for each group was 2. Amifostine was well tolerated and was associated with higher stem cell collection. Toxicity and time to engraftment were comparable between the two groups. Our preliminary results may suggest a role of amifostine in protecting stem cells during salvage chemotherapy, thus facilitating stem cell collection.

Adolescent↗
PubMed2004

Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4.

BACKGROUND: Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. RESULTS: In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings) and we report here that nestin-positive (but not nestin-negative) mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1) this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2) anti-BMP4 antibodies inhibit the nestin-positive mesenchymal stem cells conditioned medium inducing effect on astrogliogenesis. CONCLUSIONS: When thinking carefully about mesenchymal stem cells as candidates for cellular therapy in neurological diseases, their effects on resident neural cell fate have to be considered.

Animals↗
PubMed2004

The effect of stem design on end-of-stem pain in revision total knee arthroplasty.

A series of 143 revision total knee arthroplasties was evaluated using a Knee Society clinical score, radiographic assessment, and satisfaction questionnaire. Patients completed a pain drawing showing the location and severity of pain they experienced at 2 years follow-up. Two stem designs were used: a solid, fluted cobalt chrome stem (group I) and a slotted titanium stem (group II). End-of-stem pain was associated with solid cobalt chrome stems while a lower incidence of stem pain was associated with slotted titanium stems. Symptoms were intermittent and activity related in all but 2 cases, but none required component revision. The presence of end-of-stem pain did appear to be clinically significant because patients with this pain were more likely to be only somewhat satisfied or dissatisfied with their degree of pain relief compared to those without end-of-stem pain. Stem design does appear to impact the incidence of end-of-stem pain in revision total knee arthroplasty.

Arthroplasty, Replacement, Knee↗