AIM2 inflammasome is dispensable for the host defense against Pseudomonas aeruginosa infection.

Respiratory tract infection with Pseudomonas aeruginosa is a major cause of hospital—acquired pneumonia in immune—compromised individuals. Lung infection with P. aeruginosa is often associated with production of various inflammatory cytokines including IL—1β. Production of IL—1β requires proteolytic cleavage by a multiprotein complex termed inflammasome. AIM2 inflammasome recognizes foreign cytosolic double stranded DNA. A role of AIM2 in P. aeruginosa infection has not been reported previously. In this study, we found that P. aeruginosa infection induced degradation of AIM2 protein in macrophages and induction of AIM2 mRNA expression in macrophages and in the lung of mice. Interestingly, P. aeruginosa infection induced a similar level of IL—1β, IL—6 and TNF production in wild—type and AIM2—deficient mice. Similarly, no significant differences in bacterial clearance, neutrophil infiltration and NF—κB activation were observed between wild—type and AIM2—deficient mice following P. aeruginosa lung infection. Our data suggest that AIM2 inflammasome is dispensable for the host defense against P. aeruginosa infection.

Design of a hybrid implementation effectiveness cluster randomized controlled trial of delivering written exposure therapy for PTSD in underserved primary care settings.

INTRODUCTION: Posttraumatic stress disorder (PTSD) results in substantial costs to society. Prevalence of PTSD among adults is high, especially among those presenting to primary care settings. Evidence-based psychotherapies (EBPs) for PTSD are available but dissemination and implementation within primary care settings is challenging. Building Experience for Treating Trauma and Enhancing Resilience (BETTER) examines the effectiveness of integrating Written Exposure Therapy (WET) within primary care collaborative care management (CoCM). WET is a brief exposure-based treatment that has the potential to address many challenges of delivering PTSD EBPs within primary care settings. METHODS: The study is a hybrid implementation effectiveness cluster-randomized controlled trial in which 12 Federally Qualified Health Centers (FQHCs) will be randomized to either CoCM plus WET (CoCM+WET) or CoCM only with 60 patients within each FQHC. The primary aim is to evaluate the effectiveness of CoCM+WET to improve PTSD and depression symptom severity. Secondary treatment outcomes are mental and physical health functioning. The second study aim is to examine implementation of WET within FQHCs using FQHC process data and staff interviews pre- and post-intervention. Exploratory aims are to examine potential moderators and mediators of the intervention. Assessments occur at baseline, and 3- and 12-month follow-up. CONCLUSION: The study has the potential to impact practice and improve clinical and public health outcomes. By establishing the effectiveness and feasibility of delivering a brief trauma-focused EBP embedded within CoCM in primary care, the study aims to improve PTSD outcomes for underserved patients. TRIAL REGISTRATION: (Clinicaltrials.govNCT05330442).

Molecular Epidemiologic and Geo-Spatial Characterization of Staphylococcus aureus Cultured from Skin and Soft Tissue Infections from United States-Born and Immigrant Patients Living in New York City.

(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue infections (SSTIs), as well as more invasive infections. One clonal strain, S. aureus USA300, originating in the United States, has spread worldwide. We hypothesized that S. aureus USA300 would still be the leading clonal strain among US-born compared to non-US-born residents, even though risk factors for SSTIs may be similar in these two populations (2) Methods: In this study, 421 participants presenting with SSTIs were enrolled from six community health centers (CHCs) in New York City. The prevalence, risk factors, and molecular characteristics for MRSA and specifically clonal strain USA300 were examined in relation to the patients' self-identified country of birth. (3) Results: Patients born in the US were more likely to have S. aureus SSTIs identified as MRSA USA300. While being male and sharing hygiene products with others were also significant risks for MRSA SSTI, we found exposure to animals, such as owning a pet or working at an animal facility, was specifically associated with risk for SSTIs caused by MRSA USA300. Latin American USA300 variant (LV USA300) was most common in participants born in Latin America. Spatial analysis showed that MRSA USA300 SSTI cases were more clustered together compared to other clonal types either from MRSA or methicillin-sensitive S. aureus (MSSA) SSTI cases. (4) Conclusions: Immigrants with S. aureus infections have unique risk factors and S. aureus molecular characteristics that may differ from US-born patients. Hence, it is important to identify birthplace in MRSA surveillance and monitoring. Spatial analysis may also capture additional information for surveillance that other methods do not.

Kidney-targeting Smad7 gene transfer inhibits renal TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice.

AIMS/HYPOTHESIS: The TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes. METHODS: We delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF-ß/SMAD2/3-mediated fibrosis and NF-κB-dependent inflammation were evaluated. RESULTS: In this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-ß/SMAD and NF-κB signalling pathways in the kidney. CONCLUSIONS/INTERPRETATION: Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-ß/SMAD and NF-κB signalling pathways.

A Randomized Controlled Trial to Increase Cancer Screening and Reduce Depression Among Low-Income Women.

Low-income women of color receive fewer cancer screenings and have higher rates of depression, which can interfere with cancer screening participation. This study assessed the comparative effectiveness of two interventions for improving colorectal, breast, and cervical cancer screening participation and reducing depression among underserved women in Bronx, NY, with depression. This comparative effectiveness randomized controlled trial (RCT) with assessments at study entry, 6, and 12 months utilized an intent-to-treat statistical approach. Eligible women were aged 50 to 64, screened positive for depression, and were overdue for ≥ 1 cancer screening (colorectal, breast, and/or cervical). Participants were randomized to a collaborative depression care plus cancer screening intervention (CCI + PCM) or cancer screening intervention alone (PCM). Interventions were telephone-based, available in English or Spanish, delivered over 12 months, and facilitated by a skilled care manager. Cancer screening data were extracted from electronic health records. Depression was measured with a validated self-report instrument (PHQ-9). Seven hundred fifty seven women consented and were randomized (CCI + PCM, n = 378; PCM, n = 379). Analyses revealed statistically significant increases in up-to-date status for all three cancer screenings; depression improved in both intervention groups. There were no statistically significant differences between the interventions in improving cancer screening rates or reducing depression. CCI and PCM both improved breast, cervical, and colorectal cancer screening and depression in clinical settings in underserved communities; however, neither intervention showed an advantage in outcomes. Decisions about which approach to implement may depend on the nature of the practice and alignment of the interventions with other ongoing priorities and resources.

Filaggrin polymorphism P478S, IgE level, and atopic phenotypes.

BACKGROUND: Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. OBJECTIVES: To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. METHODS: In total, 116 children aged 2-5years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. RESULTS: A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88-11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37-16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01-10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93-16·60) in children with IgE level ≥100 kU L(-1) . However, the association was not evident when IgE level was < 100 kU L(-1) . CONCLUSIONS: Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.

[Primary experience and discussion on the treatment of esthesioneuroblastoma].

Objective: To summarize the preliminary experience in the treatment of esthesioneuroblastoma (ENB) and to explore the effect of age, chemotherapy, modified Kadish stage and pathological grade on the prognosis of ENB. Methods: The clinical data of 87 ENB patients from the First Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University Cancer Center between June 2002 and November 2017 were retrospectively analyzed. The modified Kadish stage was used to evaluate the extent of the lesions, and the Hyams grading system was used for pathological grading. The patients were followed up regularly to evaluate the recurrence and metastasis of the tumor. Cox proportional hazard model was used for univariate and multivariate analyses. Prognostic factors with P<0.05 in univariate analysis were included in multivariate analysis. After controlling the confounding factors, the model coefficients were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time of ENB patients was 29 months, and the 5-year overall survival rate was 39.3%. In univariate analysis, age, chemotherapy, modified Kadish stage and pathology grade were independent predictors of overall survival, while gender, radiotherapy and surgery were not prognostic factors. Multivariate analysis showed that modified Kadish stage and pathology grade were independent predictors of overall survival rate after excluding confounding factors. Conclusions: Age, chemotherapy, modified Kadish stage and pathological grade are taking important role in the overall survival rate of patients with ENB. Modified Kadish stage and pathological grade are independent predictors of overall survival rate.

Integrating Cancer Screening and Mental Health Services in Primary Care: Protocol and Baseline Results of a Patient-Centered Outcomes Intervention Study.

BACKGROUND: Low-income and minority women are significantly more likely to be diagnosed with preventable, late-stage cancers and suffer from depression than the general population. Intervention studies aiming to reduce depression to increase cancer screening among underserved minority women are sparse. METHODS: This patient-centered outcomes trial compared Collaborative Care Intervention plus Cancer Prevention Care Management (CCI+PCM) versus PCM alone. Participants from six Federally Qualified Health Centers (FQHCs) were interviewed at baseline, 6-and 12-month follow-up to monitor adherence to screening guidelines, depressive symptoms, quality of life, barriers to screening, and other psychosocial and health-related variables. RESULTS: Participants included 757 English-or Spanish-speaking women (ages 50-64) who screened positive for depression on the Patient Health Questionnaire (PHQ)-9 and were not up-to-date for breast, cervical, and/or colorectal cancer screening. CONCLUSIONS: Study methodology and baseline participant characteristics are reported to contribute to the literature on evidence-based interventions for cancer screening among underserved, depressed women.

[New system combining Hyams grading system and modified Kadish stage to evaluate the progress of esthesioneuroblastoma].

Objective:Esthesioneuroblastoma(ENB) is a sinonasal rare tumor, and the assessment on the prognosis have not been used with on consensus, our study aims to set an accuracy indicator to predict the outcomes of ENB.Method:A retrospective review was performed on 31 ENB patients. We collected 31 patients with ENB and reviewed the clinical data and pathological slides; modified Kadish stages were evaluated by otolaryngologist and imaging specialist; Hyams grading system were confirmed by two pathologists, who reviewed and paid attention to the pathological characteristics of Hyams grading system. Finally, the relation among the clinical data, pathological features and clinical outcome of these 31 ENB were analyzed by Kaplan-Meier method.Result: The Hyams grading system and modified Kadish stage were considered together seemed to evaluate the prognosis of ENB more accurately, when the scores over 6 points, the patients had the poor prognosis with the mean median survival months of 24.67±32.22, compared with the scores under 6 and the final scores reached at 4, 5, 6, 7, 8, the tumor metastasis rates were 14.3%, 16.7%, 33.3%, 50.0%, 100.0% respectively.Conclusion:Taking the Hyams grading system and modified Kadish stage into consideration, which may evaluate the prognosis of ENB more accurately.

Hypofractionated CyberKnife stereotactic radiosurgery for acoustic neuromas with and without association to neurofibromatosis Type 2.

CyberKnife stereotactic radiosurgery (CKSRS) has been proved effective in treating intra-cranial lesions. To treat acoustic neuroma (AN) patients with or without neurofibromatosis Type 2 (NF2) associations, the functional preservation of hearing, trigeminal nerve, and facial nerve are important. Twenty-one patients were treated with hypofractionated CKSRS. Fourteen non-NF2 and seven NF2 patients were enrolled. Cranial nerve function, audiograms, and magnetic resonance images (MRI) were monitored. Mean follow-up was 15 month. Tumors with volumes ranging from 0.13 to 24.8 cm3 (mean 5.4 cm3) were irradiated with the marginal dose 1800-2000 cGy/3 fractions. Tumors were treated with an 80 to 89% isodose line (mean 83%) and mean 97.9% tumor coverage. Two patients experienced hearing deterioration (16.7%) in the non-NF2 group, and 3 patients (50%) in the NF2 group. No facial or trigeminal dysfunction, brain stem toxicity, or cerebellar edema occurred. Tumor regression was seen in 9 patients (43%) and stable in 12 patients (57%). 100% tumor control rate was achieved. Hypofractionated CKSRS was not only effective in tumor control but also excellent in hearing preservation for non-NF2 AN. But for NF2 patients, although the tumor control was remarkable, hearing preservation was modest as in non-NF2 patients.

Linkages between mineralogy, fluid chemistry, and microbial communities within hydrothermal chimneys from the Endeavour Segment, Juan de Fuca Ridge.

Rock and fluid samples were collected from three hydrothermal chimneys at the Endeavour Segment, Juan de Fuca Ridge to evaluate linkages among mineralogy, fluid chemistry, and microbial community composition within the chimneys. Mössbauer, midinfrared thermal emission, and visible-near infrared spectroscopies were utilized for the first time to characterize vent mineralogy, in addition to thin-section petrography, X-ray diffraction, and elemental analyses. A 282°C venting chimney from the Bastille edifice was composed primarily of sulfide minerals such as chalcopyrite, marcasite, and sphalerite. In contrast, samples from a 300°C venting chimney from the Dante edifice and a 321°C venting chimney from the Hot Harold edifice contained a high abundance of the sulfate mineral anhydrite. Geochemical modeling of mixed vent fluids suggested the oxic-anoxic transition zone was above 100°C at all three vents, and that the thermodynamic energy available for autotrophic microbial redox reactions favored aerobic sulfide and methane oxidation. As predicted, microbes within the Dante and Hot Harold chimneys were most closely related to mesophilic and thermophilic aerobes of the Betaproteobacteria and Gammaproteobacteria and sulfide-oxidizing autotrophic Epsilonproteobacteria. However, most of the microbes within the Bastille chimney were most closely related to mesophilic and thermophilic anaerobes of the Deltaproteobacteria, especially sulfate reducers, and anaerobic hyperthermophilic archaea. The predominance of anaerobes in the Bastille chimney indicated that other environmental factors promote anoxic conditions. Possibilities include the maturity or fluid flow characteristics of the chimney, abiotic Fe2+ and S2- oxidation in the vent fluids, or O2 depletion by aerobic respiration on the chimney outer wall.

An aqueous Chlorella extract inhibits IL-5 production by mast cells in vitro and reduces ovalbumin-induced eosinophil infiltration in the airway in mice in vivo.

An aqueous extract of the edible microalga (CP) (1), has recently been tested for its immunomodulatory effects in a human clinical trial. Here, the CP extract was dialyzed and fractionated using Sephadex G 100 chromatography. The effects of a dialyzed aqueous CP extract, fraction 2 , on mast cell mediator release in vitro and ovalbumin-induced allergic airway inflammation in vivo were examined. In vitro, treatment of mouse bone marrow-derived mast cells with 2 for 18 h significantly inhibited antigen (trinitrophenyl-BSA)-induced IL-5 production. In vivo, treatment of mice with 2 during ovalbumin sensitization and stimulation process significantly reduced eosinophil and neutrophil infiltration in the airways. Moreover, fractions obtained by size exclusion chromatography of 2 inhibited IgE-dependent cytokine GM-CSF production from human cord blood-derived mast cells. Taken together, these results suggest that 2 is composed of biopolymers with anti-allergic potential.

Toll-like receptor 4-mediated activation of murine mast cells.

Toll-like receptors (TLRs) are a family of pattern recognition receptors that are critical for cellular responses to a variety of bacterial, viral, and fungal products. Mast cells are important to host survival in a number of models of bacterial infection and might act as sentinel cells in host defense. We therefore examined the expression of TLRs and associated molecules by murine bone marrow-derived mast cells (BMMCs). BMMCs and the murine mast cell line MC/9 expressed mRNA for TLR2, TLR4, and TLR6 but not TLR5 and for both adapter molecule MD-2 and signaling molecule MyD88 but lacked surface CD14. After activation with the TLR2- and TLR4-dependent stimuli Staphylococcus aureus-derived peptidoglycan and Escherichia coli-derived lipopolysaccharide (LPS), respectively, mast cells produced significant levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). To determine whether mast cells require TLR4 for cellular responses to LPS, mast cells were derived from the bone marrow cells of C3H/HeJ and C57Bl/10ScNCr mice containing a point mutation and a null mutation, respectively, in TLR4. Using these models, we demonstrated that the BMMC IL-6 and TNF-alpha responses to LPS were completely dependent on functional TLR4 with no significant LPS response observed in its absence. These findings have important implications for the mechanism of mast cell responses to pathogens and their products and suggest that different TLR4-expressing cells might have different thresholds for activation with LPS.

Internalization of FimH+ Escherichia coli by the human mast cell line (HMC-1 5C6) involves protein kinase C.

Rodent mast cells (MC) play critical roles in host defense against bacterial infection. However, bacteria-mediated signaling mechanisms in MC have not been studied. In addition, the response of human MC to bacteria is not fully investigated. This study examined the interaction between human MC and type 1 fimbriated Escherichia coli and the mechanisms involved using the human MC line HMC-1 5C6 and human cord blood-derived MC. These MC internalized significant numbers of FimH+ E. coli, but not its isogenic FimH- mutant. In HMC-1 cells, bacterial internalization was stimulated by protein kinase C (PKC) activation [short-term phorbol myristate acetate (PMA) treatment] and dramatically decreased by PKC inhibitors or PKC depletion (long-term PMA treatment). Moreover, bacterial internalization was accompanied by significant expression of PKCbeta1 and delta. Fluorescence microscopy demonstrated accumulation of PKCbeta1 on internalized bacteria. These data indicate that human MC has the capacity to internalize bacteria and PKC may be a critical intracellular mediator of this function.

Metabolic clearance of progesterone in the menstrual cycle.

PIP: To study the metabolic clearance rate (MCR) of progesterone in the normal female menstrual cycle and to estimate progesterone production rates from reported plasma concentration values, 21 normally menstruating women, 19-36 years old, were tested during various stages of the menstrual cycle. The MCR of progesterone as measured by the continuous infusion method was found to be 2510/day or 1512 1/day per sq. m, which is greater than the MCR in males, ovariectomized females, and pregnant women. The conversion rate of 20 alpha-hydroxypregn-4-en-3-one/progesterone was 10.9%. No relation was found between the day of the cycle and either the MCR or the conversion ratio, as measured in 3 women at 3 stages of the same menstrual cycle and in 3 women 3 times every other day at midcycle. The MCR appears to be relatively constant throughout the cycle. This experiment confirms a calculated progesterone production rate based on known plasma concentrations of .75-2.5 mg/day in the follicular phase and 15-50 mg/day in the luteal phase.^ieng

Protection by salvianolic acid A against adriamycin toxicity on rat heart mitochondria.

It was found that salvianolic acid A (Sai A) has potent antioxidant activity. The effects of Sai A on adriamycin-induced heart mitochondrial toxicity of rats in vitro and on adriamycin antitumor activity are investigated in this article. Malondialdehyde (MDA) formation and membrane rigidification of rat heart mitochondria intoxicated with adriamycin were significantly reduced by Sai A. In the electron spin resonance (ESR) studies, Sai A has no significant effect on the formation of adriamycin semiquinone radicals (AQ.), while hydroxyl radicals generated by electron transfer from AQ. to H2O2 were scavenged by Sai A dose-dependently. On the other hand, Sai A was shown to have no effects on the antitumor activity of adriamycin in cultured L1210 ascitic tumor cells and in mice with P388 ascite tumor. These results indicate that Sai A protects against adriamycin induced heart mitochondrial toxicity of rats, while Sai A has no antagonizing effect on the antitumor activity of adriamycin.

Traumatic brainstem deafness with normal brainstem auditory evoked potentials.

A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.

Effects of salvianolic acid A on oxygen radicals released by rat neutrophils and on neutrophil function.

Salvianolic acid A (Sai A) has demonstrated potent antioxidant activity in previous studies. In the present study, the effects of Sai A on oxygen radicals released by rat neutrophils and on neutrophil function were investigated. Superoxide anion assayed by the nitroblue tetrazolium test and hydrogen peroxide detected with redox of scopoletin were scavenged concentration dependently by Sai A in n-formyl-methionyl-leucylphenylalanine (fMLP)- and phorbol myristate acetate (PMA)-stimulated rat neutrophils. Hydroxyl radicals generated in PMA-stimulated neutrophils, measured by HPLC, also were scavenged significantly by Sai A, whereas Sai A showed no significant effects on chemotaxis toward fMLP and phagocytosis of latex beads by rat neutrophils. In addition, the intracellular free calcium and cyclic nucleotide levels of neutrophils, when stimulated by fMLP, were not affected by Sai A. These results suggest that Sai A could significantly scavenge oxygen radicals released by activated neutrophils without affecting their functional ability.

Protection by schisanhenol against adriamycin toxicity in rat heart mitochondria.

The effects of schisanhenol (Sal) on Adriamycin (ADM)-induced rat heart mitochondrial toxicity in vitro were investigated. Malondialdehyde formation, lysis, disintegration and membrane rigidification in mitochondria treated with ADM were reduced significantly by Sal. In the electron spin resonance studies, Sal did not affect significantly the formation of ADM semiquinone radicals (AQ.), whereas hydroxyl radicals generated by electron transfer from AQ.to H2O2 were scavenged by Sal dose dependently. These results indicate that Sal could protect against ADM-induced rat heart mitochondrial toxicity.

Adult reserve stem cells and their potential for tissue engineering.

Tissue restoration is the process whereby multiple damaged cell types are replaced to restore the histoarchitecture and function to the tissue. Several theories have been proposed to explain the phenomenon of tissue restoration in amphibians and in animals belonging to higher orders. These theories include dedifferentiation of damaged tissues, transdifferentiation of lineage-committed progenitor cells, and activation of reserve precursor cells. Studies by Young et al. and others demonstrated that connective tissue compartments throughout postnatal individuals contain reserve precursor cells. Subsequent repetitive single cell-cloning and cell-sorting studies revealed that these reserve precursor cells consisted of multiple populations of cells, including tissue-specific progenitor cells, germ-layer lineage stem cells, and pluripotent stem cells. Tissue-specific progenitor cells display various capacities for differentiation, ranging from unipotency (forming a single cell type) to multipotency (forming multiple cell types). However, all progenitor cells demonstrate a finite life span of 50 to 70 population doublings before programmed cell senescence and cell death occurs. Germ-layer lineage stem cells can form a wider range of cell types than a progenitor cell. An individual germ-layer lineage stem cell can form all cells types within its respective germ-layer lineage (i.e., ectoderm, mesoderm, or endoderm). Pluripotent stem cells can form a wider range of cell types than a single germ-layer lineage stem cell. A single pluripotent stem cell can form cells belonging to all three germ layer lineages. Both germ-layer lineage stem cells and pluripotent stem cells exhibit extended capabilities for self-renewal, far surpassing the limited life span of progenitor cells (50-70 population doublings). The authors propose that the activation of quiescent tissue-specific progenitor cells, germ-layer lineage stem cells, and/or pluripotent stem cells may be a potential explanation, along with dedifferentiation and transdifferentiation, for the process of tissue restoration. Several model systems are currently being investigated to determine the possibilities of using these adult quiescent reserve precursor cells for tissue engineering.