Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cell Transplantation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2005

Washout of transplanted cells from the heart: a potential new hurdle for cell transplantation therapy.

OBJECTIVE: The number of viable transplanted cells in the heart is sharply decreased shortly after cell injection. The exact mechanics of cell loss are unclear. We hypothesized that immature cardiac cells transplanted directly into rat heart could be washed out via the cardiac vasculature, and carried to other organs. METHODS: Female Fischer rats were subjected to 60 min of coronary artery occlusion followed by 3 h of reperfusion (OR group) or 4 h or permanent coronary artery occlusion (PO group). Neonatal rat cardiac cells (5x10(6)) were injected directly into the free wall of the left ventricle at either 15 min post-reperfusion (OR group) or 75 min after occlusion (PO group). At the end of the protocol, a histological analysis for transplanted cells in the heart (i.e. microscopic examination for cells in approximately 790 histogic fields within each heart) and polymerase chain reaction (PCR)-based determination of the Sry gene (a male cell marker) in the heart and other organs were performed. RESULTS: In the OR group, only 3.39+/-0.69% fields contained immature cells compared to 6.57+/-1.33% fields in the PO group (p<0.05). Cardiac blood vessels contained round, immature cardiomyocytes. PCR analysis revealed that 100% of the animals (5 of 5) in both groups had cells present in their hearts and lungs, 40% of the OR group and 60% of the PO group demonstrated cells in the liver and kidneys, and 40% of the PO group had cells in the spleen. CONCLUSION: Neonatal cardiomyocytes injected directly into the area at risk of the heart escape acutely from the infract to other organs through the vascular system of the heart; loss of cells is more prominent with reperfusion.

Animals↗
PubMed2006

In vivo imaging of bone marrow mesenchymal stem cells transplanted into myocardium using magnetic resonance imaging: a novel method to trace the transplanted cells.

BACKGROUND: In vivo imaging of the cells transplanted into the beating heart is very important for the study of the cell's retention, migration. This study was designed to find a new labeling agent to trace and visualize the transplanted cells in vivo. METHOD: BMMSCs were incubated with SPIO for 48 h. The labeling efficiency was tested through Prussian blue staining, the growth ability was evaluated through MTT, and the cells viability was tested through Trypan blue rejection method, the migratory ability was assessed with Costar Transwell plates. After 10 days of coronary ligation of the Chinese mini swine, the labeled or unlabeled cells were transplanted into the myocardium. The MRI was carried out immediately and 1-4 weeks, respectively. After MRI the hearts were excised, the segment in which injections were performed were thin cut and stained with hematoxylin-eosin and Prussian blue staining. RESULTS: There were intracytoplasmatic blue particles in nearly every cell in the Prussian blue staining. SPIO had no poison effect on the cells' growth and proliferation. The cells' viability was more than 95%. The migratory ability was not affected. The injected sites containing labeled cells could all be detected through MRI and were confirmed on pathology. After 4 weeks the injected labeled cells could still be detected through MRI. The pathology showed the injected cells could survive in the MI area, and parallel in the same direction. CONCLUSION: The cells could be efficiently and safely labeled with SPIO and the labeled cells could be reliably detected by MRI in vivo.

Animals↗
PubMed2006

Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival.

Although transplanted Schwann cells (SCs) can promote axon regeneration and remyelination and improve recovery in models of spinal cord injury, little is known about their survival and how they interact with host tissue. Using labeled SCs from transgenic rats expressing human placental alkaline phosphatase (PLAP), SC survival in a spinal cord contusion lesion was assessed. Few PLAP SCs survived at 2 weeks after acute transplantation. They died early due to necrosis and apoptosis. Delaying transplantation until 7 days after injury improved survival. A second wave of cell death occurred after surviving cells had integrated into the spinal cord. Survival of PLAP SCs was enhanced by immunosuppression with cyclosporin; delayed transplantation in conjunction with immunosuppression resulted in the best survival. In all cases, transplantation of SCs resulted in extensive infiltration of endogenous p75+ cells into the injury site, suggesting that endogenous SCs may play an important role in the repair observed after SC transplantation.

Alkaline Phosphatase↗
PubMed2003

Myoblast-based cell transplantation.

Cell transplantation is emerging as a new treatment designed tot improve the poor outcome of patients with cardiac failure. Its rationale is that implantation of contractile cells into postinfarction scars can functionally rejuvenate these areas. Primarily for practical reasons, autologous skeletal myoblasts have been the first to be tested clinically but bone marrow stromal and hematopoietic stem cells may represent an interesting alternative in select situations because of their autologous origin and their purported plasticity. However, several key issues still need to be addressed including (1) the optimal type of cells, (2) the mechanism by which cell engraftment improves cardiac function, i.e., increased contractility or limitation of remodeling, (3) the most effective strategies for optimizing cell survival, and (4) the potential benefits of cell transplantation in nonischemic heart failure. In parallel to the experimental studies designed to address these issues, initial clinical trials are underway and should hopefully allow to know whether the hopes raised by cellular therapy are met by clinically meaningful improvements in function and outcome in patients with severe left ventricular ischemic dysfunction.

Animals↗
PubMed2003

Skeletal muscle satellite cell transplantation.

Cell transplantation is currently gaining a growing interest as a potential new means of improving the prognosis of patients with cardiac failure. The basic assumption is that left ventricular dysfunction is primarily caused by the loss of a critical number of cardiomyocytes and that their replacement by new contractile cells could functionally 'regenerate' postinfarction scars in which these cells are implanted. Primarily for practical reasons, autologous skeletal myoblasts have been the first to undergo clinical trials but other cell types are also considered, particularly bone marrow stem cells which are attractive because of their autologous origin and their purported cardiomyocyte/endothelial transdifferentiation potential in response to cues present in the target organ. However, several key issues still need to be addressed including (1) the optimal type of donor cells, (2) the mechanism by which cell engraftment improves cardiac function, (3) the optimization of cell survival, and (4) the potential benefits of cell transplantation in nonischemic dilated cardiomyopathies. In parallel to the experimental studies designed to address these issues, clinical trials are underway and their results should hopefully allow the assessment of to what extent cellular therapy may improve the outcome of patients with heart failure.

Animals↗
PubMed2006

Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive cell transplantation.

Cell transplantation as a treatment for spinal cord injury is a promising therapeutic strategy whose effective clinical application would be facilitated by non-invasive delivery protocols. Cells derived from the bone marrow are particularly attractive because they can be obtained easily, expanded to large numbers and potentially used for autologous as well as allogeneic transplantation. In this study we tested the feasibility of a novel minimally invasive method--lumbar puncture (LP)--for transplanting bone marrow stromal stem cells (MSC) into a clinically relevant spinal cord contusion model. We further sought to determine optimal protocols for performing such minimally invasive cell transplantation. Sprague-Dawley rats received a moderate contusion injury at the midthoracic level followed by LP transplantation of MSC derived from transgenic rats that express the human placental alkaline phosphatase (AP) reporter gene. The recipients were analyzed histologically to evaluate the extent of cell delivery and survival at the injury site. We found that MSC delivered by LP reached the contused spinal cord tissues and exerted a significant beneficial effect by reducing cyst and injury size. Transplantation within 14 days of injury provided significantly greater grafting efficiency than more delayed delivery, and increasing MSC dosage improved cell engraftment. The techniques described here can easily be translated to patients, thus accelerating clinical application of stem cell therapies.

Alkaline Phosphatase↗
PubMed2006

Evaluation of frequency, type, and function of gap junctions between skeletal myoblasts overexpressing connexin43 and cardiomyocytes: relevance to cell transplantation.

Cell transplantation of skeletal myoblasts (SMs) is one possible treatment for repairing cardiac tissue after myocardial injury. However, inappropriate electrical coupling between grafted SMs and host cardiomyocytes may be responsible for the arrhythmias observed in clinical trials of SM transplantation. Whether functional gap junctions occur between the two cell types remains controversial. We have studied the ability of SMs to electrically couple with isolated adult rat cardiomyocytes (CMs) and assessed whether connexin43 (Cx43) overexpression enhanced gap junctional conductance (Gj). C2C12 myoblast lines overexpressing Cx43 were generated by gene transfection and clonal selection. CMs were cocultured with either SMs overexpressing Cx43 (CM-SM(Cx43)) or control SMs (CM-SM(WT)) in vitro. Gj between pairs of SMs and CMs was quantified with dual whole cell patch clamping. Formation of Gj occurred between 22% of CM-SM(WT) pairs (n=73) and 48% of CM-SM(Cx43) pairs (n=71, P<0.001). The Gj of CM-SM(Cx43) pairs (29.7+/-4.3 nS, n=21) was greater than that of CM-SM(WT) pairs (14.8+/-2.0 nS, n=12, P<0.05). The overexpression of Cx43 in SMs increased the formation of electrical communication and the steady-state conductance between SMs and CMs. Enhanced gap junctional conductance may be useful to promote the integration of transplanted SMs into the myocardium.

Animals↗
PubMedDate not supplied

Differentiation "in vitro" of primary and immortalized porcine mesenchymal stem cells into cardiomyocytes for cell transplantation.

Cell transplantation to regenerate injured tissues is a promising new treatment for patients suffering several diseases. Bone marrow contains a population of progenitor cells known as mesenchymal stem cells (MSCs), which have the capability to colonize different tissues, replicate, and differentiate into multilineage cells. Our goal was the isolation, characterization, and immortalization of porcine MSCs (pMSCs) to study their potential differentiation "in vitro" into cardiomyocytes. pMSCs were obtained from the aspirated bone marrow of Large-White pigs. After 4 weeks in culture, adherent cells were phenotypically characterized by flow cytometry and immunochemistry by using monoclonal antibodies. Primary pMSCs were transfected with the plasmid pRNS-1 to obtain continuous growing cloned cell lines. Fresh pMSCs and immortalized cells were treated with 5-azacytidine to differentiate them into cardiomyocytes. Flow cytometry analysis of isolated pMSCs demonstrated the following phenotype, CD90(pos), CD29(pos), CD44(pos), SLA-I(pos), CD106(pos), CD46(pos) and CD45(neg), CD14(neg), CD31(neg), and CD11b(neg), similar to that described for human MSC. We derived several stable immortalized MSC cell lines. One of these, called pBMC-2, was chosen for further characterization. After "in vitro" stimulation of both primary or immortalized cells with 5-azacytidine, we obtained different percentages (30%-50%) of cells with cardiomyocyte characteristics, namely, positive for alpha-Actin and T-Troponin. Thus, primary or immortalized pMSCs derived from bone marrow and cultured were able to differentiate "ex vivo" into cardiac-like muscle cells. These elements may be potentials tools to improve cardiac function in a swine myocardial infarct model.

Animals↗
PubMed2002

Anoikis: roadblock to cell transplantation?

Cell therapy, in particular liver cell transplantation, holds great therapeutic potential and is partially hindered by the high rate of apoptosis during cell isolation, cryopreservation, and engraftment. Apoptosis occurring due to cell detachment from the extracellular matrix is a phenomenon termed "anoikis." The purpose of this review is to describe signaling mechanisms pertinent to anoikis in both immortalized cell lines, but particularly in primary normal epithelial cells. The mechanisms described include integrin signaling and survival molecules, caspase activation, and the role of mitochondrial proteins in anoikis. Strategies to prevent anoikis during isolation and cryopreservation of hepatocytes are discussed.

Animals↗
PubMed2025

Frequency and Distribution of KIR Genotypes of Donors-Recipient Pairs in the Haploidentical Haematopoietic Stem Cell Transplantation Setting: Collaborative Study by the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC).

There is limited information regarding the influence of KIR genotype, compared to the HLA system, in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). This study aimed to determine the frequencies of KIR genotypes in Spanish haematologic patients undergoing haplo-HSCT. A study was conducted on 113 oncohaematological patients and their donors, treated across five centres that are members of the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC). KIR typing was performed using PCR-rSSO or PCR-SSP. KIR genotypes were identified using the KIR Allele Frequency Net Database. Among donors, the most frequent KIR genotypes were Type 1 (28.3%), Type 2 (12.4%) and Type 4 (10.6%). In patients, Genotypes 1 (23.9%), 4 (23%) and 2 (14.2%) were most prevalent. Donors exhibited AA centromeric (46%) and telomeric (59.3%) types, while patients had a higher AB centromeric frequency (52.2%). Differences were observed in the BB centromeric type (3.5% patients; 16.8% donors, p&#x2009;=&#x2009;0.002). The AB KIR genotype was the most common (70.8% donors; 75.2% patients). Most were classified as 'neutral' (61.9% donors; 73.5% patients). B-content score1 was the most common (48.7% patients; 33.6% donors). Notably, classification as best was rare (2.7% patients; 16.8% donors, p&#x2009;=&#x2009;0.002). The study highlights the distribution of KIR genotypes in haplo-HSCT patients and donors, with Genotypes 1, 2 and 4 being the most prevalent. AB KIR genotypes and B-content score 1 were dominant. Moreover, KIR genotypes ID may serve as criteria for future investigation about the immunogenetic predisposition to malignant haematological diseases.

Humans↗
PubMed2002

A biodegradable composite scaffold for cell transplantation.

Cell transplantation is rapidly becoming a therapeutic option to treat disease and injury. However, standard techniques for cell seeding on non-woven polymer meshes or within gels may not be suitable for immediate implantation or surgical manipulations of freshly isolated cells. Therefore, a biodegradable composite system was developed as a way to rapidly entrap cells within a support of predefined shape to potentially facilitate cell delivery into a target site (e.g. meniscal tears in the avascular zone). The composite construct consisted of freshly isolated cells, in this case pig chondrocytes, entrapped in a fibrin gel phase and dispersed throughout the void volume of a polyglycolic acid (PGA) non-woven mesh. Composites were cultured for up to 4 weeks. In vitro degradation of fibrin gel was evaluated via gel-entrapped urokinase. At 28 days in culture, glycosaminoglycan (GAG) content per cell in the composite scaffolds was 2.6 times that of the PGA-only cell construct group and 88% that of native pig cartilage. Total collagen content per cell in the composite scaffolds was not significantly different from the PGA-only cell construct group (P > 0.02) and represented 40% of the value determined for native cartilage. Varying the concentration of entrapped urokinase could effect controlled degradation of fibrin gel.

Absorbable Implants↗
PubMed2005

Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases.

The conditioning prior to allogeneic stem cell transplantation was originally designed as a myeloablative conditioning, designed to eliminate malignant or genetically abnormal cells and then use the transplant procedure for rescue of the patients or to replace missing bone marrow products. However, allografts can induce effective graft vs. malignancy effects and can also eliminate undesirable hematopoietic stem cells in patients with genetic disorders and autoimmune diseases, thus documenting that alloreactive effects mediated by donor lymphocytes post-grafting can play a major role in eliminating hematopoietic cell of host origin, as well as provide effective immunotherapy for the treatment of disease recurrence. The efficacy of donor lymphocyte infusion (DLI) could be improved by activation with rIL-2 or by donor immunization. The cumulative experience over the years suggesting that alloreactive donor lymphocytes were most effective in eliminating tumor cells of host origin resulted in an attempt to reduce the intensity of the conditioning in preparation for the transplant procedure used for the treatment of hematological and other malignancies as well as life-threatening non-malignant disorders for which allogeneic stem cell transplantation may be indicated. Our working hypothesis proposed that the myeloablative conditioning which is hazardous and may be associated with early and late side effects, may not be required for treatment of patients with any indication for allogeneic stem cell transplantation. Instead, nonmyeloablative conditioning based on the use of reduced intensive preparatory regimen, also known as nonmyeloablative stem cell transplantation, may be sufficient for engraftment of donor stem cells while avoiding procedure-related toxicity and mortality, followed by elimination of undesirable cells of host origin by post-transplant effects mediated by alloreactive donor lymphocytes infused along with donor stem cells or administered subsequently as DLI. Improvement of the immediate outcome of stem cell transplantation using NST due to a significant decrease in transplant related mortality has broadened the spectrum of patients eligible for allogeneic stem cell transplantation, including elderly patients and other patients with less than optimal performance status. Likewise, the safer use of stem cell transplantation prompted expanding the scope of potential indications for allogeneic stem cell transplantation, such as metastatic solid tumors and autoimmune disorders, which now are slowly becoming much more acceptable. Current strategies focus on the need to improve the capacity of donor lymphocytes to eliminate undesirable malignant and non-malignant hematopoietic cells of host origin, replacing abnormal or malignant stem cells or their products with normal hematopoietic stem cells of donor origin, while minimizing procedure-related toxicity and mortality and improving the quality of life by reducing the incidence and severity of hazardous acute and chronic GVHD.

Animals↗
PubMed2003

Impact of transplanted CD34+ cell dose in allogeneic unmanipulated peripheral blood stem cell transplantation.

The impact of the CD34+ cell dose on chronic graft-versus-host disease (cGVHD) and the clinical outcome was analyzed in 41 consecutive adult patients submitted to allogeneic peripheral blood stem cell transplantation from HLA-identical siblings. The patients were classified into 'low' or 'high' CD34+ cell dose groups based on whether they received less or more than a median CD34+ cell dose of 10.5 x 10(6)/kg, respectively. There was a significant difference in the incidence of extensive cGVHD (low vs high group, 25.0 vs 66.7%, P=0.021) and relapse (47.6 vs 20.0%, P=0.049) between the two groups. With a median follow-up of 335 days, the 3-year survival estimate for the whole population was 47.9%, while that for the low and high groups was 29.9 and 67.8%, respectively (P=0.0434). An inverse relation was noted between the relapse rate and the incidence of extensive cGVHD (P=0.043). It would appear reasonable that the optimal dose of CD34+ cells should be determined based on the disease status or aggressiveness of the malignant cells in each patient. Yet, in the case of patients with a high risk of relapse, transplantation with a CD34+ cell dose of >10.5 x 10(6)/kg would seem to be acceptable to minimize the risk of relapse.

Adolescent↗
PubMed2006

Allogeneic marrow stem-cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy.

PURPOSE: To investigate the influence of donor type (human leukocyte antigen [HLA] -identical sibling donor versus HLA-A-, HLA-B-, HLA-Cw-, HLA-DRB1-, and HLA-DQB1-identical unrelated donors, or so-called 10/10) on the outcome of patients who underwent allogeneic stem-cell transplantation (alloSCT), adjusting for other prognostic factors, in patients with standard-risk hematologic malignancy. PATIENTS AND METHODS: Between March 2000 and January 2003, we prospectively investigated the outcome of 236 consecutive patients with standard-risk malignancy from 12 French centers. Fifty-five patients underwent alloSCT from an unrelated HLA-identical donor at the allelic level, whereas 181 patients received an alloSCT from an HLA-identical sibling. Diagnoses included acute leukemia (n = 175), chronic myeloid leukemia (n = 43), and myelodysplastic syndrome (MDS; n = 18). All patients received unmodified marrow graft following myeloablative conditioning with cyclophosphamide and total-body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate in all patients. RESULTS: In multivariable analysis, overall survival and transplantation-related mortality were adversely influenced by recipient cytomegalovirus (CMV) -positive serology, age of donor older than 37 years, and the occurrence of acute grade > or = II GVHD. Event-free survival rates were lower for patients with recipient CMV-positive serology. Acute grades II to IV GVHD rates were higher for patients with chronic myeloid leukemia (CML). No factor was found to influence either relapse or acute grades III to IV GVHD. The effect of donor type was nonsignificant for all criteria. CONCLUSION: In patients with standard-risk malignancy, transplantation from unrelated HLA-allellically matched donors led to outcomes similar to those from HLA-identical sibling donors.

Adult↗
PubMed2000

Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats.

To determine whether liver repopulation with cell transplantation could be of therapeutic value in acute hepatic failure, it is necessary to establish the fate of transplanted hepatocytes. This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and proliferation of transplanted hepatocytes. Syngeneic hepatocytes were transplanted intrasplenically 24-30 h after induction of liver injury by D-galactosamine (GalN). Portosystemic shunting was analysed with 99m-Tc-labelled albumin microspheres. GalN-treated rats showed characteristic hepatic necrosis, inflammation, gamma-glutamyl transpeptidase activation, and regenerative activity, without increased portosystemic shunting (>99% 99m-Tc activity was in the liver in normal and GalN-treated rats). Transplanted cells entered hepatic sinusoids promptly and were observed in liver plates at 48 h. The number of transplanted cells increased in GalN-treated rats by approximately seven-fold (range two- to 12-fold), along with evidence for DNA synthesis between 3 and 14 days after cell transplantation and greater prevalence of larger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the time required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeutic strategies.

Animals↗
PubMed2004

Donor leukocyte infusions in relapsed Hodgkin's lymphoma following allogeneic stem cell transplantation: CD3+ cell dose, GVHD and disease response.

Nine patients with advanced Hodgkin's lymphoma (HL) who had undergone allogeneic stem cell transplantation (allo-SCT) received donor leukocyte infusions (DLIs) for treatment of persistent or progressive disease (PD). A total of 15 DLIs were performed, with four patients receiving more than one DLI. In four patients, prior salvage chemotherapy was administered. The median CD3+ cell dose administered was 77.5 x 10(6)/kg (range 5-285). GVHD developed in all but one patient. The response rate was 4/9 (44%). Three of these four responders developed GVHD and 3/4 had received chemotherapy. No correlation was observed between CD3+ cell dose infused and disease response. At the latest follow-up, three patients are alive and six have expired (PD n=3, nonrelapse mortality n=3). The median response duration was 7 months (range 4-9), with one response currently ongoing. These data suggest that DLIs for immunotherapy of recurrent HL have significant activity, although they frequently leads to GVHD. The small sample size does not allow any conclusion as to whether chemotherapy administration increases the chance of response. The CD3 cell dose infused does not seem to correlate with disease response.

Adolescent↗