Development and characterization of a humanized mouse model of osteoarthritis.

OBJECTIVE: In light of the role of immune cells in OA pathogenesis, the development of sophisticated animal models closely mimicking the immune dysregulation during the disease development and progression could be instrumental for the preclinical evaluation of novel treatments. Among these models, immunologically humanized mice may represent a relevant system, particularly for testing immune-interacting DMOADs or cell therapies before their transfer to the clinic. Our objective, therefore, was to develop an experimental model of OA by destabilization of the medial meniscus (DMM) in humanized mice. METHOD: Irradiated 5-week-old NOD/LtSz-scid IL2Rγnull (NSG) mice were humanized by intravenous injection of CD34+ human hematopoietic stem cells. The engraftment efficiency was evaluated by flow cytometry 17 weeks after the humanization procedure. Humanized and non-humanized NSG mice underwent DMM or sham surgery and OA development was assessed 1, 6, and 12 weeks after the surgery. RESULTS: 120 days after the humanization, human T and B lymphocytes, macrophages and NK cells, were present in the blood and spleen of the humanized NSG mice. The DMM surgery induced articular cartilage and meniscal alterations associated with an increase in OA and the meniscal score. Moreover, the surgery triggered an inflammatory response that was sustained at a low grade in the DMM group. CONCLUSIONS: Our study shows for the first time the feasibility of inducing OA by DMM in humanized mice. This novel OA model could constitute a useful tool to bridge the gap between the preclinical and clinical evaluation of immune interacting DMOADs and cell-based therapies.

Toxicological impact of organic ultrafine particles (UFPs) in human bronchial epithelial BEAS-2B cells at air-liquid interface.

Air pollution has significant health effects worldwide, and airborne particles play a significant role in these effects. Ultrafine particles (UFPs) have an aerodynamic diameter of 0.1 µm or less, can penetrate deep into the respiratory tree, and are more toxic due to their large specific surface area, which should adsorb organic compounds. The aim of this study is to show the toxicological effects of UFPs with high organic content at low dose on BEAS-2B cells through at air-liquid interface (ALI) exposure using a Vitrocell® technology and a miniCAST (Combustion Aerosol Standard) generator. In conjunction with this approach, chemical analysis of particles and gas phase was performed to evaluate the presence of polycyclic aromatic hydrocarbons (PAHs). Chemical analyses confirmed the presence of PAHs in UFPs. With this experimental setup, exposure of the BEAS-2B cells induced neither cytotoxicity nor mitochondrial dysfunction. However, an increase of oxidative stress was observed, as assessed through Nrf2, NQO1, HO-1, CuZnSOD, MnSOD, and Catalase gene expression, together with significant induction of genes related to xenobiotic metabolism CYP1A1 and CYP1B1. Negative regulation of inflammatory genes expression (IL-6 and IL-8) was present three hours after the exposition to the UFPs. Taken together, this experimental approach, using repeatable conditions, should help to clarify the mechanisms by which organic UFPs induce toxicological effects.

Potential therapeutic roles of stem cells in ischemia-reperfusion injury.

Ischemia-reperfusion injury (I/RI), produced by an initial interruption of organ blood flow and its subsequent restoration, contributes significantly to the pathophysiologies of stroke, myocardial infarction, renal I/RI, intestinal I/RI and liver I/RI, which are major causes of disability (including transplant failure) and even mortality. While the restoration of blood flow is required to restore oxygen and nutrient requirements, reperfusion often triggers local and systemic inflammatory responses and subsequently elevate the ischemic insult where the duration of ischemia determines the magnitude of I/RI damage. I/RI increases vascular leakage, changes transcriptional and cell death programs, drives leukocyte entrapment and inflammation and oxidative stress in tissues. Therapeutic approaches which reduce complications associated with I/RI are desperately needed to address the clinical and economic burden created by I/RI. Stem cells (SC) represent ubiquitous and uncommitted cell populations with the ability to self-renew and differentiate into one or more developmental 'fates'. Like immune cells, stem cells can home to and penetrate I/R-injured tissues, where they can differentiate into target tissues and induce trophic paracrine signaling which suppress injury and maintain tissue functions perturbed by ischemia-reperfusion. This review article summarizes the present use and possible protective mechanisms underlying stem cell protection in diverse forms of ischemia-reperfusion.

Dosimetric and microdosimetric analyses for blood exposed to reactor-derived thermal neutrons.

Thermal neutrons are found in reactor, radiotherapy, aircraft, and space environments. The purpose of this study was to characterise the dosimetry and microdosimetry of thermal neutron exposures, using three simulation codes, as a precursor to quantitative radiobiological studies using blood samples. An irradiation line was designed employing a pyrolytic graphite crystal or-alternatively-a super mirror to expose blood samples to thermal neutrons from the National Research Universal reactor to determine radiobiological parameters. The crystal was used when assessing the relative biological effectiveness for dicentric chromosome aberrations, and other biomarkers, in lymphocytes over a low absorbed dose range of 1.2-14 mGy. Higher exposures using a super mirror will allow the additional quantification of mitochondrial responses. The physical size of the thermal neutron fields and their respective wavelength distribution was determined using the McStas Monte Carlo code. Spinning the blood samples produced a spatially uniform absorbed dose as determined from Monte Carlo N-Particle version 6 simulations. The major part (71%) of the total absorbed dose to blood was determined to be from the 14N(n,p)14C reaction and the remainder from the 1H(n,γ)2H reaction. Previous radiobiological experiments at Canadian Nuclear Laboratories involving thermal neutron irradiation of blood yielded a relative biological effectiveness of 26 ± 7. Using the Particle and Heavy Ion Transport Code System, a similar value of ∼19 for the quality factor of thermal neutrons initiating the 14N(n,p)14C reaction in soft tissue was determined by microdosimetric simulations. This calculated quality factor is of similar high value to the experimentally-derived relative biological effectiveness, and indicates the potential of thermal neutrons to induce deleterious health effects in superficial organs such as cataracts of the eye lens.

[Cancer plans apply to surgical treatment of prostate cancer: A geographically isolated center balance]. / Les plans cancer appliqués au traitement chirurgical du cancer de prostate : le bilan d'un centre isolé géographiquement.

INTRODUCTION: Since 2003, fight against cancer was structured by 3 national cancer programs (CP). The objective of this study is to evaluate the application of these measures in the case of surgical prostate cancer (PCa) treatment in a geographically isolated center. MATERIAL: Monocentric retrospective study carried in a 100-bed clinic located 2hours away from a Cancer Regional Reference Center. Between August 2009 and December 2014, 251 consecutive patients were treated by total laparoscopic prostatectomy (TLP). Fifty-seven patients (22.7 %) received a secondary treatment after TLP. The study focused on the delay between prostate biopsies and PTL, the traceability of AD elements, the return of active patients, inclusion in clinical trials (GETUG 17, GETUG 20 and GETUG 22). Data were collected in September 2016. The follow-up defined by the time between the date of the last visit and the prostate biopsy allows a median follow-up of 43.1 months (2.4-80.5). RESULTS: All elements of the CAP are totally gathered on 45 % of the patients (113/251). Thirty-four (13.5 %) patients were active at the time of the intervention. Thirty-one (91.2 %) will return to an identical activity after a median work stoppage of 1.7 month (0.25-6). Fourteen percent (35/251) of the patients are eligible to a clinical trial. Seventeen percent (6/35) of them were proposed to one of a trial after multidisciplinary meeting and 5.7 % (2/35) are eventually included in one trial. CONCLUSION: CP define a course of high quality care. A better transparency of the founding of the enforceable measures and a better consideration for the local specificities should facilitate their application. The TLP treat the PCa with the reasonable objective of a return to an identical professional activity. The multidisciplinary meeting does not guarantee the participation to clinical trial, which depends mainly on distance from the Cancer Regional Reference Center and the vigilance of the Urologist. LEVEL OF EVIDENCE: 4.

[Fatal central nervous system hemorrhage during acute lymphoblastic leukemia induction]. / Hémorragie cérébrale fatale en cours d'induction d'une leucémie aiguë lymphoblastique.

Intracerebral hemorrhage (ICH) remains a cause of death in hematologic malignancies. Asparaginase represents a key agent in the treatment of acute lymphoblastic leukemia (ALL). The toxicity of asparaginase includes coagulopathy such as thrombotic or bleeding tendency. We report a case of fatal cerebral hemorrhage in a 12-year-old girl treated for ALL. Cerebral hemorrhage occurred after three injections of L-asparaginase. The patient presented with hypofibrinogenemia (0.36g/L), associated with thrombocytopenia (24,000/mm3). Despite maximal medical and surgical treatment (platelets and fresh-frozen plasma transfusions, red blood cells transfusion, fibrinogen replacement therapy, and craniotomy discharge), the patient died. L-asparaginase is well known for its prothrombotic action. By inhibiting the synthesis of fibrinogen and factors V, VII, VIII, and IX, it causes an increased risk of bleeding, including intracranial bleeding. Predictive scores for ICH onset have been established but there is no consensus on the management of coagulation disorders induced by L-asparaginase. It is recommended to check fibrinogen and antithrombin (AT) blood values in order to substitute them if they drop to < 1 g/L for fibrinogen and < 60% for AT. The management of asparaginase-induced ICH does not differ from that of ICH of other origin. The risk of death is high, and surgical treatment has not proven superior to medical therapy in terms of mortality rates and 6-month survival. Further studies are needed to define consensus guidelines for coagulation disorders induced by asparaginase and also to define the specific management in cases of ICH in childhood hematological malignancies.

[Early type 2 neurofibromatosis and congenital retinal hamartoma]. / Neurofibromatose de type 2 précoce et hamartome rétinien congénital.

Neurofibromatosis type 2 (NF2) is a heritable syndrome characterized by multifocal proliferation of neural crest-derived cells. It has long been regarded as an adolescent- and adult-onset disease. We report here on a case of a 6-year-old girl with infantile-onset clinical signs. The girl, who had a history of amblyopia and congenital retinal hamartoma, presented with rough dimness of visual acuity. Cerebral magnetic resonance imaging found a left voluminous fronto-temporal tumor including the chiasma and optical nerves. Vestibular and cervical nerve schwannomas were also found. She underwent a first neurosurgical partial excision and histopathology revealed meningioma. Postoperative radiotherapy was necessary due to a secondary increase of the tumor size. Subsequent molecular testing revealed a NF2 gene abnormality. NF2 can become evident in infancy but clinical early symptomatology is often different: ocular symptoms and neurological problems are common. There is no consensus on the treatment of tumors involving the central and peripheral nervous system, abstention being usual. In case of severe signs, surgery and radiotherapy can be proposed. The diagnosis of a hamartoma must lead to multidisciplinary follow-up.

[Life-threatening hypercalcemia as the initial presentation of childhood acute lymphoblastic leukemia]. / Hypercalcémie menaçante révélatrice d'une leucémie aiguë lymphoblastique de l'enfant.

Hypercalcemia in childhood acute lymphoblastic leukaemia (ALL) is a well-known but uncommon complication. Here, we report a case of B-ALL in which the first signs were life-threatening hypercalcemia associated with diffuse osteolytic lesions with no hematologic abnormalities. We draw attention to the difficulties formally establishing the ALL diagnosis. Bone marrow examinations must be repeated if necessary. Furthermore, biological, cytogenetic, and molecular aspects need to be investigated. Measurement of intact PTH can exclude hyperparathyroidism. PTHrP is possibly involved in hypercalcemia processes induced by tumor cells. The t(17;19) translocation and its E2A-HLF transcript fusion, which have been thought to be a poor prognostic factor, must be determined. Regarding severe hypercalcemia control, treatment is based on both underlying disease management and serum calcium level reduction with aggressive hydration and if necessary bisphosphonates.

Objectively measured physical activity, sedentary time and sleep duration: independent and combined associations with adiposity in canadian children.

OBJECTIVE: To examine independent and combined associations among objectively measured movement/non-movement behaviors (moderate-to-vigorous-intensity physical activity (MVPA), total sedentary time and sleep duration) and adiposity indicators in a sample of Canadian children. METHODS: A cross-sectional study was conducted on 507 children aged 9-11 years from Ottawa, Canada. Movement/non-movement behaviors were assessed using an Actigraph GT3X+ accelerometer over 7 days (24-h protocol). Outcomes included percentage body fat (bioelectrical impedance) and waist-to-height ratio. RESULTS: After adjustment for age, sex, ethnicity, maturity offset, fast food consumption, annual household income and highest level of parental education, MVPA was inversely and sedentary time positively associated with adiposity indicators, whereas sleep duration was not. However, only MVPA remained significantly associated with adiposity indicators after additional adjustment for the other movement/non-movement behaviors. Combined associations using tertiles of the three movement/non-movement behaviors showed that higher levels of MVPA were associated with lower adiposity indicators, irrespective of total sedentary time and sleep duration. CONCLUSIONS: Higher levels of MVPA were associated with lower adiposity in this sample of children regardless of sedentary time and sleep duration. Although correlational in nature, these findings suggest that future efforts of obesity reduction should focus more on increasing MVPA than on reducing sedentary time or increasing sleep duration to maximize the effectiveness of interventions.

Bronchogenic cyst of the tongue in an infant.

Bronchogenic cyst of the tongue is rare. We report the case of a 17-month baby who has a lingual lesion. MRI shows a well-defined cystic lesion. Treatment consisted of a complete resection and histology found a pseudostratified respiratory type epithelium. Only 10 pediatric cases of bronchogenic cyst of the tongue have been reported in the literature. MRI is the imaging modality of choice and treatment is always surgical. The final diagnosis is made by histology.

Assessing the potential clinical utility of transplantations of neural and mesenchymal stem cells for treating neurodegenerative diseases.

Treatments for neurodegenerative diseases have little impact on the long-term patient health. However, cellular transplants of neuroblasts derived from the aborted embryonic brain tissue in animal models of neurodegenerative disorders and in patients have demonstrated survival and functionality in the brain. However, ethical and functional problems due to the use of this fetal tissue stopped most of the clinical trials. Therefore, new cell sources were needed, and scientists focused on neural (NSCs) and mesenchymal stem cells (MSCs). When transplanted in the brain of animals with Parkinson's or Huntington's disease, NSCs and MSCs were able to induce partial functional recovery by promoting neuroprotection and immunomodulation. MSCs are more readily accessible than NSCs due to sources such as the bone marrow. However, MSCs are not capable of differentiating into neurons in vivo where NSCs are. Thus, transplantation of NSCs and MSCs is interesting for brain regenerative medicine. In this chapter, we detail the methods for NSCs and MSCs isolation as well as the transplantation procedures used to treat rodent models of neurodegenerative damage.

Melanotic neuroectodermal tumor of infancy: case report and review of the literature.

Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a rare but distinct neoplastic entity in infancy. Diagnosis is usually made before the age of 12 months. The common clinical presentation is a rapidly growing mass of the pre-maxillary area. Its surface is unevenly pigmented. To affirm the diagnosis a biopsy is necessary. Few cases of malignancy have been described (5% of cases). Adequate surgical excision is the treatment of choice. Recurrence rate is about 10 to 15% within 5 years. We report in this article the case of a newborn with MNTI illustrating that an R0 surgical excision can be correlated to a favourable prognosis. In this case the 5 years follow up didn't show any local or distant recurrence.

New lines of GFP transgenic rats relevant for regenerative medicine and gene therapy.

Adoptive cell transfer studies in regenerative research and identification of genetically modified cells after gene therapy in vivo require unequivocally identifying and tracking the donor cells in the host tissues, ideally over several days or for up to several months. The use of reporter genes allows identifying the transferred cells but unfortunately most are immunogenic to wild-type hosts and thus trigger rejection in few days. The availability of transgenic animals from the same strain that would express either high levels of the transgene to identify the cells or low levels but that would be tolerant to the transgene would allow performing long-term analysis of labelled cells. Herein, using lentiviral vectors we develop two new lines of GFP-expressing transgenic rats displaying different levels and patterns of GFP-expression. The "high-expresser" line (GFP(high)) displayed high expression in most tissues, including adult neurons and neural precursors, mesenchymal stem cells and in all leukocytes subtypes analysed, including myeloid and plasmacytoid dendritic cells, cells that have not or only poorly characterized in previous GFP-transgenic rats. These GFP(high)-transgenic rats could be useful for transplantation and immunological studies using GFP-positive cells/tissue. The "low-expresser" line expressed very low levels of GFP only in the liver and in less than 5% of lymphoid cells. We demonstrate these animals did not develop detectable humoral and cellular immune responses against both transferred GFP-positive splenocytes and lentivirus-mediated GFP gene transfer. Thus, these GFP-transgenic rats represent useful tools for regenerative medicine and gene therapy.

[Quality score in pathological report of prostate biopsies improve professional practice]. / La mention systématique d'un indice de qualité dans les comptes rendus de biopsies prostatiques influence les pratiques professionnelles.

OBJECTIVE: Evaluate the influence on professional practices of a systematic indication of a quality score (IGap) in the conclusion of the pathologic reports (CRFS) of prostatic biopsies (PB). MATERIALS AND METHOD: Prospective study carried over 339 consecutive 10 core extended standardized PB performed by two urologists over a period of 22 months. The CRFS were computerized. The conclusion included an IGap ranking from 0 to 1, automatically computed from three criteria: the average length of the PB, the number of PB with identified capsules or periprostatic tissues and the average number of fragments per PB. The quality was best when the index is close to 1. A quarterly monitoring of the average of IGap was performed for the two urologists. The student t test was used to compare the averages. RESULTS: The average of IGap of the urologists A and B was, respectively, of 0.57 (s=0.1; n=184) and 0.66 (s=0.1; n=155): p<0.001. At quarter 1, the averages of IGap of the urologists A and B are, wads of respectively, of 0.47 (s=0.14; n=25) and 0.7 (s=0.12; n=14) (p<0.001). The significant difference of the average of IGap of the urologists A and B observed on quarter 1 progressively decline to disappear from the quarter 4. CONCLUSIONS: At equivalent protocols, the urologists do not necessarily perform PB of comparable quality. A systematic indication of an IGap in the pathological reports of PB seems to prompt the urologists to modify their practices toward an improvement of the score.

[Length of needle and size of prostatic biopsies influence identification of capsular and extracapsular elements]. / La longueur des biopsies prostatiques conditionne l'identification des éléments capsulaires et périprostatiques.

OBJECTIVE: To evaluate the influence of the length of prostate biopsies (PB) on identification of prostatic capsule and periprostatic tissue. MATERIALS AND METHOD: A prospective study was carried out in one center by two urologists during 22 months on 339 consecutive protocols of standardized ten-needle PB (PSA<10ng/ml regardless of digital rectal examination). Pathologic reports were standardized. The conclusion of the pathologic report included the average length of the ten-needle PB (Lm) and the number of prostatic core biopsies on which pathologist identified prostatic capsule and periprostatic tissue (BCI). Protocols of PB were spread in 16 groups depending on the value of Lm in millimeter: [0-1], [1-2], [2-3]... [15-16]. Relationship between Lm's and BCI's was evaluated using the linear regression and the correlation coefficient (r). RESULTS: Average Lm=10.7 (2.1-15.7; s=2.3) (n=339). Average BCI=6.6 (0-10; s=2.3) (n=339). The value of IGap increased when the value of Lm increased (r=0.89). CONCLUSIONS: The pathologists better identify the capsule of the prostate and the periprostatic tissue when the PB's are of large size. PB's of small size are of poor quality either for samplings of the prostatic gland or samplings of the capsule and the periprostatic tissues.

[Development of a pathological quality score of prostate biopsies]. / Elaboration d'un indice de qualité anatomopathologique des biopsies prostatiques.

OBJECTIVES: Develop a score allowing the pathologist to objectively report on the overall quality of extended standardized prostatic biopsy (EPB). METHODS: A prospective study was carried out on 339 consecutive protocols of 10 core EPB (PSA<10 ng/ml). Reports are standardized and computerized. The conclusion of the reports includes an estimate of the overall quality of the EPB based on three items to classify the protocols in three groups: protocol of "good" quality (group 1), "medium" quality (group 2) and "poor" quality (group 3). The score (IGap) is automatically computed from three objective criteria also shown on the conclusion of the report: the average length of the 10 biopsies (LM), the number of biopsies on which capsular elements can be identified (BCI) and the average number of fragment per biopsy (Fm). The IGap index rank from 0 to 1. The average IGap of the three groups is computed using the t-test. RESULTS: The average IGaps of the groups 1, 2 and 3 are respectively of 0,65 (0,37-0,89 ; n=250), 0,52 (0,36-0,71 ; n=69) and 0,43 (0,22-0,6 ; n=20), (p<0,001). CONCLUSION: IGap is a pertinent score reporting objectively of the overall quality of EPB. An IGap close to one indicates a good quality of EPB. An IGap close to zero indicate a poor quality of EPB.

[Meaning of the Quantiferon TB Gold tube test in tuberculosis screening among the hospital staff in case of very old or recent positive skin tests]. / Signification de Quantiféron TB Gold en tube en dépistage de la tuberculose parmi le personnel hospitalier en cas d'intradermoréactions positives très anciennes ou récentes.

UNLABELLED: The tuberculin skin test or PPD performed on health professionals evaluates delayed hypersensitivity to a Mycobacterium tuberculosis (Mt) antigen mixture. A very positive or increased area of induration indicates latent tuberculosis. Yet, prescribing a treatment is often difficult because of the test's poor specificity. OBJECTIVE: To determine if the T-lymphocytes of the proband exposed to specific Mt antigens to secrete interferon-gamma (IFN-gamma) can be measured; observe an immunizing response to cellular mediation improves T it this specificity? PATIENTS AND METHODS: The Department of Occupational Health at CHR of Metz performed a Quantiferon TB Gold (tube method, Cellestis) test on three groups of employees distributed according to the anteriority of a very positive IDR (>15mm). The test measures by method ELISA, the quantity of IFN-gamma secreted by the lymphocytes T collected in 1ml of total blood, after in vitro stimulation by antigens ESAT-6, CFP-10 and TB7.7. Group I is composed of 53 people (46 women [W] and 7 men [M]) and related to a recent discovery of October 2006 and June 2007, whereas group II, includes 28 of them (25W and 3M), is made of subjects with known very positive PPD for eight to 27 years. The age (41 years on average) and the sex-ratio are identical for these two groups. Group III is made of employees having made a tuberculosis there is more than 30 years. In the group I, the rate of IFN was supervised at the end of the treatment among patients who received it. RESULTS: The test Quantiferon TB Gold was positive at 15 subjects of group I (13W and 2M), that is to say 28.3%, and unspecified in one case (1.9%); positive at nine subjects of group II (9W), that is to say 32.1%. These rates of positivity are not significantly different. According to the experts consulted in group I, an antituberculosis treatment was proposed 11 times with 10 effective treatments (one refusal). A proportioning after treatment was carried out among six patients. The rate of IFN remained positive at five of the six supervised patients. This test made it possible to avoid the treatment of the 37 employees with test Quantferon TB negative Gold found over the nine months period of recruitment of group I. The choice not to treat was facilitated. CONCLUSION: The test Quantiferon indeed allows to eliminate the false positive of the skin test (1.6) so avoiding useless, expensive treatments and unwanted effects of antituberculosis medicines . On the other hand, the persistent positivity of this test 30 years after one firstly infection or after a contact does not allow to use it at present as certain control of a latent infection, unless having a negative value known about the hiring pa.

[Neonatal consequences of maternal smoking during pregnancy]. / Conséquences du tabagisme in utero pour le nouveau-né.

In utero tobacco consumption is a serious public health problem in France; it is very frequent and the long term consequences are not only numerous but also misinterpreted by our population. 25 to 29% of women arrive at the end of their pregnancy without stopping smoking and 50% of non smoking mothers live in an environment polluted by tobacco during pregnancy. The authors would like to stress the gravity of this situation. At the maternity hospital in Nîmes, 358 women who gave birth at term and after a normal pregnancy were enrolled in a survey and monitored with thiocyanate for their tobacco consumption. Birth weight, height, and cranial perimeter of the infants were noted at birth. Results confirmed earlier work on this subject: the three variables studied were consistently weakened by the mother's addiction to tobacco. The authors recall previous medical literature on the pathophysiology and other consequences on the brain: such as I.Q. behavior, sudden infant death syndrome, vascular alterations with possible long-term complications, as well as pulmonary alterations on which there has recently been much research. The question is raised as to why this problem is so neglected in our society and what could be done to change this state of affairs.

Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated mice.

BACKGROUND: BM cells have been shown to give rise to progeny of various cell lineages, including cells in lung and liver. This investigation evaluated whether purified BM mononuclear cells and side population (SP) cells that have hematopoietic stem-cell activity also had this property; whether a TBI preparative regimen was necessary for engraftment; and where BM-derived cells were engrafted. METHODS: Either 1-3 million BM mononuclear cells or 2000 BM SP cells from transgenic enhanced green fluorescent protein-expressing (EGFP) mice were transplanted i.v. to unirradiated or 7-9.5 Gy irradiated recipients. RESULTS: Flow cytometric analysis showed that lung cells (mean 45%, range 4-70%) and liver cells (mean 4%, range 0.4-8.3%) from irradiated, but not unirradiated recipients, were EGFP donor-derived. Similar results were obtained transplanting BM mononuclear cells or SP cells. Morphologically, donor-derived cells in the lung were primarily monocytes and macrophages. Additionally, lung fibroblasts and Type I, but not Type II, alveolar cells and rare cells in the bronchial epithelium were donor BM derived. In the liver, Kupffer cells, inflammatory cells and small clusters of hepatocytes, but not bile duct cells, were donor-derived. DISCUSSION: BM mononuclear and SP cells generated progeny in some compartments of the lung and liver, but only in TBI recipients. Stem cells in BM can contribute to repair of tissue injury in some compartments, but not to the same extent in the lung and liver.