Showing papers on "Transplantation published in 2001"
TL;DR: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life.
Abstract: Background Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. Methods We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. Results Kaplan–Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent...
3,540 citations
TL;DR: After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.
Abstract: Background Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. Methods We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who underwent sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of –3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. Results The mean (±SD)...
2,114 citations
TL;DR: In vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells are described, depicting humanES cells as a source of transplantable neural precursors for possible nervous system repair.
Abstract: The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube-like structures in the presence of fibroblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differentiated into neurons, astrocytes, and oligodendrocytes. After transplantation into the neonatal mouse brain, human ES cell-derived neural precursors were incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.
1,982 citations
TL;DR: The current criteria for OLT based on tumor size may be modestly expanded while still preserving excellent survival after OLT, and only pT4 stage and total tumor diameter remained statistically significant in multivariate analysis.
1,934 citations
TL;DR: It is reported that embryonic angiogenesis in mice was not affected by deficiency of PlGF, andTransplantation of wild-type bone marrow rescued the impairedAngiogenesis and collateral growth in Pgf−/− mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow–derived cells.
Abstract: Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PlGF (Pgf-/-). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf-/- mice. However, loss of PlGF impaired angiogenesis, plasma extravasation and collateral growth during ischemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders.
1,664 citations
TL;DR: There is accumulating evidence that T‐cell‐mediated dominant control of self‐reactive T‐cells contributes to the maintenance of immunologic self‐tolerance and its alteration can cause autoimmune disease.
Abstract: There is accumulating evidence that T-cell-mediated dominant control of self-reactive T-cells contributes to the maintenance of immunologic self-tolerance and its alteration can cause autoimmune disease. Efforts to delineate such a regulatory T-cell population have revealed that CD25+ cells in the CD4+ population in normal naive animals bear the ability to prevent autoimmune disease in vivo and, upon antigenic stimulation, suppress the activation/proliferation of other T cells in vitro. The CD25+ CD4+ regulatory T cells, which are naturally anergic and suppressive, appear to be produced by the normal thymus as a functionally distinct subpopulation of T cells. They play critical roles not only in preventing autoimmunity but also in controlling tumor immunity and transplantation tolerance.
1,600 citations
TL;DR: Several diseases that are associated with inappropriate activation of the chemokine network are examined, including cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease.
Abstract: We examine here several diseases that are associated with inappropriate activation of the chemokine network. Detailed comment has been restricted to pathological states for which there are compelling data either from clinical observations or animal models. These include cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease. Discussion focuses on therapeutic directions in which the rapidly evolving chemokine field appears to be headed.
1,393 citations
TL;DR: The reconstruction of large bone segments is an important clinical problem, and none of the approaches proposed thus far have proved very effective.
Abstract: To the Editor: The reconstruction of large bone segments is an important clinical problem, and none of the approaches proposed thus far have proved very effective. In animals, repair and functional...
1,350 citations
TL;DR: A novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allogRAFTing.
1,344 citations
TL;DR: In this article, the authors describe a technique for operative dislocation of the hip, based on detailed anatomical studies of the blood supply, which combines aspects of approaches which have been reported previously and consists of an anterior dislocation through a posterior approach with a 'trochanteric flip' osteotomy.
Abstract: Surgical dislocation of the hip is rarely undertaken. The potential danger to the vascularity of the femoral head has been emphasised, but there is little information as to how this danger can be avoided. We describe a technique for operative dislocation of the hip, based on detailed anatomical studies of the blood supply. It combines aspects of approaches which have been reported previously and consists of an anterior dislocation through a posterior approach with a 'trochanteric flip' osteotomy. The external rotator muscles are not divided and the medial femoral circumflex artery is protected by the intact obturator externus. We report our experience using this approach in 213 hips over a period of seven years and include 19 patients who underwent simultaneous intertrochanteric osteotomy. The perfusion of the femoral head was verified intraoperatively and, to date, none has subsequently developed avascular necrosis. There is little morbidity associated with the technique and it allows the treatment of a variety of conditions, which may not respond well to other methods including arthroscopy. Surgical dislocation gives new insight into the pathogenesis of some hip disorders and the possibility of preserving the hip with techniques such as transplantation of cartilage.
1,223 citations
TL;DR: It is proposed that PPARγ coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.
TL;DR: Success is reported with intramyocardial skeletal muscle transplantation in a patient with severe ischaemic heart failure and there was evidence of contraction and viability in the grafted scar on echocardiography and positron emission tomography 5 months later.
01 Jan 2001
TL;DR: For example, in this paper, the authors randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year.
Abstract: Background Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson’s disease has proved beneficial in open clinical trials However, whether this intervention would be more effective than sham surgery in a controlled trial is not known Methods We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson’s disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally In the patients who underwent sham surgery, holes were drilled in the skull but the dura was not penetrated The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of –30 to 30 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement Results The mean (±SD) scores on the global rating scale for improvement or deterioration at one year were 00±21 in the transplantation group and i04± 17 in the sham-surgery group Among younger patients (60 years old or younger), standardized tests of Parkinson’s disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=001 for scores on the Unified Parkinson’s Disease Rating Scale; P=0006 for the Schwab and England score) There was no significant improvement in older patients in the transplantation group Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18 F-fluorodopa uptake on positron-emission tomography or postmortem examination After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa Conclusions Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson’s disease and result in some clinical benefit in younger but not in older patients (N Engl J Med 2001;344:
TL;DR: The findings suggest that vitD3 acts directly on Th cells and can, in the absence of APC, enhance the development of a Th2 phenotype and augment the expression of the transcription factors c-maf and GATA-3.
Abstract: 1,25-Dihydroxyvitamin D3 (vitD3) is an immunoregulatory hormone with beneficial effects on Th1 mediated autoimmune diseases. Although the inhibitory effects of vitD3 on macrophages and dendritic cells are well documented, any direct effects of vitD3 on Th cell development are not clearly defined. Using CD4 Mel14 T cells derived from mice on a BALB/c and a C57BL/6 genetic background we examined the effect of vitD3 on Th cell development. We demonstrated that vitD3 affects Th cell polarization by inhibiting Th1 (IFN- production) and augmenting Th2 cell development (IL-4, IL-5, and IL-10 production). These effects were observed in cultures driven with splenic APC and Ag, as well as with anti-CD3 and anti-CD28 alone, indicating that CD4 cells can also be direct targets for vitD3. The enhanced Th2 development by vitD3 was found in both BALB/c and C57BL/6 mice. An increased expression of the Th2-specific transcription factors GATA-3 and c- maf correlated with the increased production of Th2 cytokines after vitD3 treatment. The vitD3-induced effects were largely mediated via IL-4, because neutralization of IL-4 almost completely abrogated the augmented Th2 cell development after vitD3 treatment. These findings suggest that vitD3 acts directly on Th cells and can, in the absence of APC, enhance the development of a Th2 phenotype and augment the expression of the transcription factors c-maf and GATA-3. Our findings suggest that the beneficial effects of vitD3 in autoimmune diseases and transplantation operate through prevention of strong Th1 responses via the action on the APC, while simultaneously directly acting on the T cell to enhance Th2 cell development. The Journal of Immunology, 2001, 167: 4974 – 4980.
TL;DR: It is shown here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for β-galactosidase expression.
Abstract: Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.
TL;DR: A number of the more prominent clinical practice guidelines for the adults are discussed, including the recommendation that the protein-energy nutritional status in patients with advanced chronic renal failure should be assessed by a panel of measures rather than by any single measure.
TL;DR: In patients given high-dose chemotherapy, with or without radiation, for the treatment of hematologic cancer,allogeneic peripheral-blood cells used for hematopoietic rescue restore blood counts faster than allogeneic bone marrow, without increasing the risk of graft-versus-host disease.
Abstract: Background In recipients of allogeneic hematopoietic-cell transplants, peripheral-blood cells mobilized with the use of filgrastim (recombinant granulocyte colony-stimulating factor) engraft more rapidly than bone marrow. However, the relative effects of these techniques on the rates of acute and chronic graft-versus-host disease, overall survival, and disease-free survival have not been determined in randomized studies. Methods Between March 1996 and July 1999, 172 patients (12 to 55 years of age) with hematologic cancer were randomly assigned to receive either bone marrow or filgrastim-mobilized peripheral-blood cells from HLA-identical relatives for hematopoietic rescue after the treatment of hematologic cancer with high doses of chemotherapy, with or without radiation. Results The recovery of both neutrophils and platelets was faster with peripheral-blood cells than with marrow (P<0.001 for both comparisons). The cumulative incidence of grade II, III, or IV acute graft-versus-host disease at 100 days ...
TL;DR: Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and the results show persistent insulin secretion, which is consistent with good glycemic control.
Abstract: Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5-17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance-stimulated glucose levels of 12.5+/-1.9 and 20.0+/-2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3+/-0.3 and 7.5+/-0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66+/-0.06 nmol/l, increasing to 1.29+/-0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA1c level decreased from 8.3+/-0.5% to the current level of 5.8+/-0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post-islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation.
TL;DR: High levels of cardiomyocyte death occur for at least 4 days after grafting into injured hearts, in large part due to ischemia.
TL;DR: Tumor diameter and number of nodules in correlation with the histopathologic grading were predictive of a vascular invasion only in HCC larger than 5 cm, which is a safe and effective long‐term treatment for small HCC in cirrhosis.
TL;DR: Umbilical-cord blood from unrelated donors can restore hematopoiesis in adults who receive myeloablative therapy and is associated with acceptable rates of severe acute and chronic GVHD.
Abstract: Background Umbilical-cord blood from unrelated donors who are not HLA-identical with the recipients can restore hematopoiesis after myeloablative therapy in children. We studied the use of transplantation of umbilical-cord blood to restore hematopoiesis in adults. Methods Sixty-eight adults with life-threatening hematologic disorders received intensive chemotherapy or total-body irradiation and then transplants of HLA-mismatched umbilical-cord blood. We evaluated the outcomes in terms of hematologic reconstitution, the occurrence of acute and chronic graft-versus-host disease (GVHD), relapses, and event-free survival. Results Of the 68 patients, 48 (71 percent) received grafts of umbilical-cord blood that were mismatched for two or more HLA antigens. Of the 60 patients who survived 28 days or more after transplantation, 55 had neutrophil engraftment at a median of 27 days (range, 13 to 59). The estimated probability of neutrophil recovery in the 68 patients was 0.90 (95 percent confidence interval, 0.85 t...
TL;DR: It is concluded that transplantation of a marginal kidney is associated with a significant survival benefit when compared with maintenance dialysis and the average increase in life expectancy for MDK recipients compared with the WLD cohort was 5 yr, although this benefit varied from 3 to 10 yr depending on the recipient's characteristics.
Abstract: . An increasing number of cadaveric kidney transplants are now performed with organs from donors who would have been deemed unsuitable in earlier times. Although good allograft outcomes have been obtained with these marginal donor transplants, it is unclear whether recipients of marginal kidney transplants achieve a reduction in long-term mortality as do recipients of “ideal” kidneys. Patients with end-stage renal disease registered on the cadaveric renal transplant waiting list between January 1, 1992, and June 30, 1997, were studied for mortality risks according to three outcomes: wait-listed on dialysis treatment with no transplant (WLD); transplantation with marginal donor kidney (MDK); and “ideal” or optimal donor kidney transplantation (IDK). Thirty-four percent of wait-list registrants had received a cadaveric kidney transplant by June 30, 1998. Of these, 18% received a marginal kidney that had one or more of the following pretransplant factors: donor age >55 yr, non-heartbeating donor, cold ischemia time >36 h, and donor hypertension or diabetes mellitus of > 10 yr duration. Five-year graft and patient survival was 53% and 74% for MDK recipients compared with 67% ( P P
TL;DR: A number of guidelines were established for creating an index of disease severity to estimate survival in patients with chronic liver disease and it was determined that such a disease severity index should rely on a few, readily available, objective variables that would be generally applicable to a heterogeneous group of patients with end-stage liver disease.
TL;DR: The use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.
Journal Article•
TL;DR: The ideal substance for soft-tissue augmentation still eludes physicians, but fat grafting through a blunt cannula seems to be the safest of all of the fillers used; in the hands of an experienced surgeon, it can provide long-lasting, natural-appearing structural changes.
TL;DR: This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers, and suggest the need for intensive efforts at coronary disease prevention in young adults.
Abstract: Background—Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. Methods and Results—Intravascular ultrasound was performed in 262 heart transplant recipients 30.9±13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4±13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness ≥0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were anal...
TL;DR: It is estimated that more than 500,000 bone-grafting procedures are performed annually in the United States, with approximately half of these procedures related to spine fusion, indicating a shortage in the availability of musculoskeletal donor tissue traditionally used in these reconstructions.
Abstract: It is estimated that more than 500,000 bone-grafting procedures are performed annually in the United States, with approximately half of these procedures related to spine fusion. These numbers easily double on a global basis and indicate a shortage in the availability of musculoskeletal donor tissue traditionally used in these reconstructions (Fig. 1).
Fig. 1:
United States trends in musculoskeletal tissue donors. Source: United Network for Organ Sharing and the Musculoskeletal Transplant Foundation.
This reality has stimulated a proliferation of corporate interest in supplying what is seen as a growing market in bone-substitute materials (Fig. 2). These graft alternatives are subjected to varying degrees of regulatory scrutiny, and thus their true safety and effectiveness in patients may not be known prior to their use by orthopaedic surgeons. It is thus important to gain insight into this emerging class of bone-substitute alternatives.
Fig. 2:
United States sales of bone graft and bone substitutes. Source: Orthopedic Network News, industry estimates.
The biology of bone grafts and their substitutes is appreciated from an understanding of the bone formation processes of osteogenesis, osteoinduction, and osteoconduction.
Graft osteogenesis: The cellular elements within a donor graft, which survive transplantation and synthesize new bone at the recipient site.
Graft osteoinduction: New bone realized through the active recruitment of host mesenchymal stem cells from the surrounding tissue, which differentiate into bone-forming osteoblasts. This process is facilitated by the presence of growth factors within the graft, principally bone morphogenetic proteins (BMPs).
Graft osteoconduction: The facilitation of blood-vessel incursion and new-bone formation into a defined passive trellis structure.
All bone graft and bone-graft-substitute materials can be described through these processes.
Fresh autogenous cancellous and, to a lesser degree, cortical bone are benchmark graft materials that allograft and bone substitutes attempt to match in in vivo performance. They incorporate all of the above properties, are …
TL;DR: Evidence is provided for a novel, noninvasive approach for targeting potential therapeutic factors to the central nervous system using genetically-modified hematopoietic cells enter the CNS and differentiate into microglia after bone-marrow transplantation.
Abstract: Gene therapy in the central nervous system (CNS) is hindered by the presence of the blood-brain barrier, which restricts access of serum constituents and peripheral cells to the brain parenchyma. Expression of exogenously administered genes in the CNS has been achieved in vivo using highly invasive routes, or ex vivo relying on the direct implantation of genetically modified cells into the brain. Here we provide evidence for a novel, noninvasive approach for targeting potential therapeutic factors to the CNS. Genetically-modified hematopoietic cells enter the CNS and differentiate into microglia after bone-marrow transplantation. Up to a quarter of the regional microglial population is donor-derived by four months after transplantation. Microglial engraftment is enhanced by neuropathology, and gene-modified myeloid cells are specifically attracted to the sites of neuronal damage. Thus, microglia may serve as vehicles for gene delivery to the nervous system.