Community Connectedness as a Moderator of the Association between Intersectional Microaggressions and Alcohol Use among Sexual and Gender Minoritized People of Color.

Background: Researchers have documented associations between discrete conceptualizations of microaggressions (e.g., sexual identity, gender identity, and racial identity microaggressions) and alcohol use among sexual and gender minoritized people of color (SGM-POC). However, little is known about the association between intersectional microaggressions and alcohol use among SGM-POC. Moreover, protective factors such as community connectedness have been examined via similar discrete conceptualizations instead of examining SGM-POC community connectedness with other SGM-POC individuals. Objectives: The purpose of this study was to explore the association between intersectional microaggressions and alcohol use among SGM-POC and test whether different types of community connectedness moderated this association. Methods: Cross-sectional data were collected from a sample of 267 SGM-POC individuals. Four moderation analyses were done to analyze whether different types of community connectedness (sexual identity, racial identity, gender identity, and SGM-POC identity community connectedness) were moderators of the association of intersectional microaggressions and alcohol use. Results: Intersectional microaggressions were significantly positively correlated with alcohol use. Furthermore, SGM-POC community connectedness moderated this association such that the association was stronger for individuals with higher levels of SGM-POC community connectedness, but not lower levels of SGM-POC community connectedness. Conclusions: These findings showcase the importance of assessing for intersectional microaggressions as a risk factor for alcohol use. Similarly, the findings suggest that SGM-POC community connectedness may be a protective factor against alcohol use for SGM-POC.

O te peinas, o te haces rolos: Intersectional discrimination, identity conflict, and mental health among Latinx sexual minoritized adults.

OBJECTIVES: People of color with minoritized sexual identities (e.g., lesbian, gay, bisexual, queer) experience identity-based challenges from outside and within their communities. Through the integrative lens of minority stress theory and intersectionality, the present study examined identity conflict, also known as conflicts in allegiances-the perceived incongruence between one's sexual and ethnic identities-as a statistical mediator of the association between intersectional discrimination (heterosexist discrimination experienced within the Latinx community and ethnic discrimination experienced within the lesbian, gay, bisexual, transgender, and queer [LGBTQ +] community) and mental health outcomes (depression and anxiety). METHOD: A cross-sectional sample of 452 Latinx sexual minoritized adults living in the United States participated in the study. The PROCESS macro (Model 4; Hayes, 2018) was used to test the hypothesis that heterosexist discrimination experienced within the Latinx community and ethnic discrimination experienced within the LGBTQ + community are associated with depression and anxiety indirectly through identity conflict. In each mediation model, outness to family was included as a covariate, along with participant age, education, generation status, and language preference. RESULTS: Approximately 37% of participants had clinically significant depression scores and 54% had clinically significant anxiety scores. As expected, experiences of intersectional discrimination (i.e., Latinx heterosexist discrimination and LGBTQ + ethnic discrimination) were indirectly associated with depression and anxiety through higher levels of identity conflict. CONCLUSIONS: Findings increase awareness of unique psychosocial factors that may underlie mental health inequities affecting Latinx adults with minoritized sexual identities. Such knowledge can facilitate the development of culturally responsive interventions that best support this diverse population by addressing intersectional minority stressors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation.

Directed differentiation of human pluripotent stem cells to kidney organoids brings the prospect of drug screening, disease modelling and the generation of tissue for renal replacement. Currently, these applications are hampered by organoid variability, nephron immaturity, low throughput and limited scale. Here, we apply extrusion-based three-dimensional cellular bioprinting to deliver rapid and high-throughput generation of kidney organoids with highly reproducible cell number and viability. We demonstrate that manual organoid generation can be replaced by 6- or 96-well organoid bioprinting and evaluate the relative toxicity of aminoglycosides as a proof of concept for drug testing. In addition, three-dimensional bioprinting enables precise manipulation of biophysical properties, including organoid size, cell number and conformation, with modification of organoid conformation substantially increasing nephron yield per starting cell number. This facilitates the manufacture of uniformly patterned kidney tissue sheets with functional proximal tubular segments. Hence, automated extrusion-based bioprinting for kidney organoid production delivers improvements in throughput, quality control, scale and structure, facilitating in vitro and in vivo applications of stem cell-derived human kidney tissue.

A critical examination of disparities in eating disorder symptoms by sexual orientation among US adults in the NESARC-III.

OBJECTIVE: Sexual minoritized persons evidence higher prevalence of eating disorders than heterosexual persons, yet it is unclear which specific symptoms drive these disparities. Empirical evidence also documents the importance of considering subclinical eating disorder presentations, as well as potential differentiation in expression of eating disorder symptoms based on gender. The current study complements that of Kamody et al. (2020), who examined sexual orientation-based disparities in eating disorder diagnoses using a nationally representative sample of the US adult population. METHOD: Using the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III), we compared the prevalence of eating disorder symptoms across sexual minority status separately for men and women. RESULTS: Sexual minoritized men were more likely than heterosexual men to report body mass index (BMI) < 18.5 kg/m2 (odds ratio [OR] = 1.76), thus, being screened into questions about restrictive eating. Sexual minoritized women were more likely than heterosexual women to endorse ever engaging in a binge-eating episode (OR = 2.25) and engaging in weekly binge eating for at least 3 months (OR = 1.58), thus, being screened into follow-up questions about binge eating. Sexual minoritized men were more likely than heterosexual men to fear gaining weight even when at their lowest weight (OR = 4.35) and experience a loss of control when overeating (OR = 3.13). DISCUSSION: Sexual orientation-based disparities in eating disorder symptom endorsement were nuanced when stratifying the entire sample by gender. Findings expand previous research on disparities in clinical/diagnosed eating disorders, highlighting the importance of assessing symptomology beyond diagnosis, as well as the intersectional influence of sexual orientation and gender, in both research and practice.

Bilateral acute lower limb ischemia secondary to complete embolization of cardiac myxoma.

Cardiac myxomas are the most common benign cardiac tumors in adults that can present with peripheral embolization. Complete detachments of myxomas are rare and tend to cause aortoiliac embolism. We report a case of a middle-aged woman with bilateral popliteal artery and segmental renal artery embolisms secondary to a completely detached cardiac myxoma. This case highlights cardiac myxomas as an important cause of acute limb ischemia and that it is not excluded by a normal echocardiogram result.

Let's get real: Identity concealment, burnout, and therapeutic relationship quality among psychology trainees with concealable stigmatized identities.

Identity concealment thwarts psychological needs of authenticity and belonging, both of which are important for mental health and relationship building. Through the lens of minority stress theory and relational-cultural theory, the present study examined whether identity concealment in the workplace by psychology trainees is indirectly associated with greater burnout and poorer therapeutic relationship quality. To test this hypothesis, a parallel mediation analysis was conducted on data from 335 clinical and counseling psychology doctoral trainees with concealable stigmatized identities using Hayes's (2018) PROCESS macro. As expected, identity concealment at a practicum or internship site was negatively associated with authenticity and belonging, both of which were negatively associated with burnout and positively associated with therapeutic relationship quality. Furthermore, identity concealment was associated with lower therapeutic relationship quality and greater burnout indirectly through lower authenticity and lower belonging. Findings suggest trainees who engage in more identity concealment at their clinical training sites may be at increased risk for burnout and poorer relationships with clients due to limited opportunities for authenticity and belonging. Future research is encouraged to longitudinally examine the impact of identity concealment on professional burnout and relationships, as well as potential protective factors. Such knowledge can support the development of interventions and policies that foster safer, more welcoming work environments for trainees with concealable stigmatized identities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Co-occurring suicidal ideation and alcohol-related problems: An intersectional analysis of Native American and White adults with minoritized sexual identities.

BACKGROUND: Disparities in suicidal ideation (SI) and alcohol use disorder (AUD) are evident in both Native American and minoritized sexual identity groups, relative to non-Hispanic White and heterosexual groups. However, Native Americans report lower drinking and binge drinking rates than White adults. Persons with intersecting identities, specifically Native Americans with minoritized sexual identities, may be at greater risk for SI and drinking, binge drinking, and AUD than White and Native American heterosexual adults. METHODS: Five years (2015-2019) of National Survey of Drug Use and Health data were combined (N = 130,157). Multinomial logistic regressions tested racial (Native American vs White) and sexual identity (lesbian/gay/bisexual vs heterosexual) differences in odds of SI, drinking, and co-occurring SI + drinking, versus neither SI/drinking. Subsequent analyses examined SI + binge drinking, and SI + AUD. RESULTS: Compared to White heterosexual adults, Native American heterosexual adults reported lower co-occurring SI + drinking odds, whereas Native American sexual minoritized adults reported higher odds. Native American sexual minoritized groups showed greater co-occurring SI + binge drinking odds and greater co-occurring SI + AUD odds compared to White heterosexual adults. Native American sexual minoritized adults showed greater SI only compared to White sexual minoritized adults. Sexual minoritized Native Americans showed higher odds of co-occurring SI + drinking, binge drinking, and AUD than White heterosexual adults. CONCLUSIONS: Native American sexual minoritized groups showed higher likelihood of co-occurring SI + drinking, binge drinking, and AUD relative to both White and Native American heterosexual adults. Disparities warrant outreach for suicide and AUD prevention for Native American sexual minoritized adults.

Status, sexual capital, and intraminority body stigma in a size-diverse sample of gay men.

Gay men are more likely than heterosexual men to experience social pressure based on body weight, shape, and muscularity, which may drive disparities in body image concerns and eating disorders. Utilizing a sample of 1723 gay men living in the United States, the present study examined whether sociodemographic factors (used as proxies for status and sexual capital) and frequency of attending gay-specific establishments or gatherings (community involvement) were associated with gay men's experiences of negative or discriminatory pressures based on body size and shape specifically from other gay men (intraminority body stigma). Experiences of intraminority body stigma were significantly more common among gay men who identified as higher-weight (r = 0.28), less masculine (r = -0.21), less wealthy (r = -0.21), younger (r = -0.21), or people of color (ds = 0.25-0.28). Furthermore, indicators of low status and sexual capital were indirectly associated with less frequent community involvement via more frequent experiences of intraminority body stigma. In addition to frequency, the valence of interactions between gay men should be considered when assessing body image and eating disorder risk in this population. Future research is encouraged to examine intraminority body stigma as an intersectional source of intraminority stress to inform prevention and treatment efforts for gay men.

An examination of theory-based suicidal ideation risk factors in college students with multiple marginalized identities.

Social marginalization increases the risk of suicidal ideation (SI) among individuals with diverse identities, yet research examining the effects of marginalization has focused on one identity. Emerging adulthood is a critical period of identity development and the age group with the highest rates of SI. Considering the challenges of living in potentially heterosexist, cissexist, racist, and sizeist environments, we tested whether possessing multiple marginalized identities was associated with severity of SI through factors proposed in the interpersonal-psychological theory (IPT) and the three-step theory (3ST) of suicide and if mediation paths were moderated by sex. A sample of 265 college students completed a cross-sectional online survey assessing SI and constructs related to IPT and 3ST. The number of marginalized identities was generated by adding minoritized sexual orientation, race/ethnicity other than non-Hispanic White, body mass index >25 kg/m2, sexual attraction to same sex but identified as heterosexual, and gender-fluid identity. In IPT multiple mediation analyses, possessing more marginalized identities was associated with SI severity through burdensomeness and hopelessness, but not belonging. Indirect paths through burdensomeness and belonging were moderated by sex. For 3ST, possessing more marginalized identities was associated with SI severity through hopelessness and psychological pain, but not social connection or meaning in life. Future research should consider intersecting social identities and test mechanisms by which multiply marginalized college students develop resilience to SI risk factors, such as support within their marginalized groups, to inform suicide assessment and intervention efforts on college campuses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development and Validation of the Gay-Specific Intraminority Stigma Inventory (G-SISI): Initial Evidence Underpinned by Intraminority Stress Theory.

There is currently a lack of measures testing intraminority stress within gay men. Therefore, the current study sought to develop and psychometrically test the Gay-Specific Intraminority Stigma Inventory (G-SISI). Based on a content review of the literature and a panel of experts, a pool of items assessing gay men's perceived exposure to a range of discriminatory attitudes from other gay men was generated. Utilizing a randomly split sample of 1723 gay men between the ages of 19 and 79 years, an exploratory factor analysis was first performed (n = 861). The remaining unexamined data were then used to conduct a confirmatory factor analysis (n = 862). The results support a six-factor model: (1) Age Stigma, (2) Socioeconomic Stigma, (3) Gay Non-Conformity Stigma, (4) Racial Stigma, (5) Gender Expression Stigma, and (6) Body Stigma. Cronbach's alpha for the total scale was 0.90 and for the subscales ranged from 0.60 to 0.85. Sociodemographic factors and measures of community involvement were differentially associated with the G-SISI subscales, providing evidence of construct validity. The findings demonstrate initial support for the dimensionality and validity of the G-SISI, which targets modifiable factors (e.g., identity-based stigma) that may increase stress and reduce community coping resources among gay men with diverse identities.

Mediating effects of a weight-inclusive health promotion program on maladaptive eating in women with high body mass index.

Research shows that individuals with a body mass index (BMI) over 30 have experienced an 11-fold increase in restrictive eating and a 7-fold increase in binge eating since the 1990s. Most health promotion programs for higher-weight individuals have not been developed with the high eating disorder risk for this population in mind. The purpose of current study was to test two hypothesized mechanisms underlying improvement in maladaptive eating patterns shown in a weight-inclusive health promotion program designed for women with BMIs at or above 30. Participants (N = 40) were primarily White (93 %), 30-45 years old (M = 39.83, SD = 4.34) with BMIs ranging from 30 to 45 kg/m2 (M = 37.42, SD = 3.58). Using the MEMORE macro, we tested a parallel mediation model hypothesizing that internalized weight stigma and intuitive eating would explain improvements on two subscales from the Three-Factor Eating Questionnaire-R18 after a 6-month program. Total effects of the program on uncontrolled (b = -3.76, SE = 0.64, p < .0001) and emotional eating (b = -1.79, SE = 0.34, p < .0001) were significant. The indirect effects (IE) of internalized weight stigma on uncontrolled eating (IE = 1.59, SE = 0.79, 95 % CI = 0.46, 3.49) and emotional eating (IE = 0.67, SE = 0.40, 95 % CI = 0.11, 1.68) were also significant. Likewise, the IEs of intuitive eating on uncontrolled eating (IE = 2.09, SE = 0.70, 95 % CI = 0.60, 3.38) and emotional eating (IE = 1.03, SE = 0.43, 95 % CI = 0.08, 1.82) were significant. These findings indicate that weight-inclusive health promotion programs that directly address weight bias and eating according to cues from the body may help higher-weight individuals improve maladaptive eating patterns via reductions in internalized weight stigma and increases in intuitive eating.

Elevated risk of substance use disorder and suicidal ideation among Black and Hispanic lesbian, gay, and bisexual adults.

OBJECTIVE: Black and Hispanic persons who identify as lesbian, gay, or bisexual (LGB) experience health disparities relative to non-Hispanic White and heterosexual groups respectively, including higher rates of suicidal ideation (SI) and substance use disorder (SUD). To elucidate intersectional risk, we used a large national sample to examine rates of SI, SUD, and their co-occurrence (SI + SUD) at the intersection of sexual identity and race/ethnicity. METHOD: Data were from five years (2015-2019) of the National Survey of Drug Use and Heath (unweighted N = 189,127). Multinomial logistic regressions with persons without SI and SUD as references were stratified by gender and controlled for survey year, age, education, marital status, and income. RESULTS: Compared to same-race and same-gender heterosexual adults, White, Black, and Hispanic LGB men and women showed higher odds of SI (AOR = 2.86-4.45), SUD (AOR = 1.23-3.01), and SI + SUD (AOR = 2.72-6.85). Compared to same-gender White heterosexual adults, Black and Latinx heterosexual men and women showed lower odds of SI (AORs = .54-.65), SUD (AORs = .52-.78) and SI + SUD (AORs = .41-.57). Compared to same-gender White LGB adults, Black and Hispanic women, but not men, showed lower SI odds (AORs = .58-.72). Compared to same-gender White heterosexual adults, Black and Hispanic LGB men and women showed higher odds of SI (AORs = 1.71-2.51) and SI + SUD (AORs = 1.91-2.97). CONCLUSIONS: Consistent with research showing effects of multiple minority stress on behavioral health, adults with intersecting racial/ethnic and sexual minority identities showed increased odds of SI, SUD, and SI + SUD relative to Non-Hispanic White heterosexual peers. Black, Hispanic, and White LGB adults may benefit from screening and intervention for SI and SUD.

Isomer-Resolved Imaging of Prostate Cancer Tissues Reveals Specific Lipid Unsaturation Profiles Associated With Lymphocytes and Abnormal Prostate Epithelia.

Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variation between pathologists, prompting investigation of biomolecular markers. Comprising around 50% of cellular mass, and with known metabolic variations in cancer, lipids provide a promising target for molecular pathology. Here we apply isomer-resolved lipidomics in combination with imaging mass spectrometry to interrogate tissue sections from radical prostatectomy specimens. Guided by the histopathological assessment of adjacent tissue sections, regions of interest are investigated for molecular signatures associated with lipid metabolism, especially desaturation and elongation pathways. Monitoring one of the most abundant cellular membrane lipids within these tissues, phosphatidylcholine (PC) 34:1, high positive correlation was observed between the n-9 isomer (site of unsaturation 9-carbons from the methyl terminus) and epithelial cells from potential pre-malignant lesions, while the n-7 isomer abundance was observed to correlate with immune cell infiltration and inflammation. The correlation of lipid isomer signatures with human disease states in tissue suggests a future role for isomer-resolved mass spectrometry imaging in assisting pathologists with prostate cancer diagnoses and patient stratification.

Explant outgrowth, propagation and characterization of human pericytes.

OBJECTIVE: Pericytes are critical cellular components of the microvasculature that play a major role in vascular development and pathologies, yet their study has been hindered by lack of a standardized method for their isolation and growth. Here we report a method for culturing human pericytes from a readily available tissue source, placenta, and provide a thorough characterization of resultant cell populations. METHODS: We developed an optimized protocol for obtaining pericytes by outgrowth from microvessel fragments recovered after enzymatic digestion of human placental tissue. We characterized outgrowth populations by immunostaining, by gene expression analysis, and by functional evaluation of cells implanted in vivo. RESULTS: Our approach yields human pericytes that may be serially expanded in culture and that uniformly express the cellular markers NG2, CD90, CD146, alpha-SMA, and PDGFR-beta, but lack markers of smooth muscle cells, endothelial cells, and leukocytes. When co-implanted with human endothelial cells into C.B-17 SCID/bg mice, human pericytes invest and stabilize developing human endothelial cell-lined microvessels. CONCLUSIONS: We conclude that our method for culturing pericytes from human placenta results in the expansion of functional pericytes that may be used to study a variety of questions related to vascular biology.

Engineering of multifunctional gels integrating highly efficient growth factor delivery with endothelial cell transplantation.

Transplantation of Bcl-2-transduced human umbilical vein endothelial cells (ECs) in protein gels into the gastrocnemius muscle improves local reperfusion in immunodeficient mouse hosts with induced hind limb ischemia. We tested the hypothesis that incorporation of local, sustained growth factor delivery could enhance and accelerate this effect. Tissue engineering scaffolds often use synthetic polymers to enable controlled release of proteins, but most synthetic delivery systems have major limitations, most notably hydrophobicity and inefficient protein loading. Here, we report the development of a novel alginate-based delivery system for vascular endothelial growth factor-A(165) (VEGF) that exhibits superior loading efficiency and physical properties to previous systems in vitro. In vivo, VEGF released from alginate microparticles within protein gels was biologically active and, when combined with EC transplantation, led to increased survival of transplanted cells at 28 days. The composite graft described also improved early (14 days) tissue perfusion and late (28 days) muscle myoglobin expression, a sign of recovery from ischemia, compared with EC transplantation and VEGF delivery separately. We conclude that our improved approach to sustained VEGF delivery in tissue engineering is useful in vivo and that the integration of high efficiency protein delivery enhances the therapeutic effect of protein gel-based EC transplantation.

Testicular tumour, could it be benign? A clinical conundrum.

Testicular vasculitis (TV) is a cause of testicular infarction (TI) which can lead to significant morbidity and rarely mortality. Polyarteritis Nodosa (PAN) is the most common vasculitis that leads to testicular infarction (TI). This case report describes the retrospective tissue diagnosis of autoimmune vasculitis in a middle aged Caucasian male who developed left unilateral orchalgia and a hard, palpable testicular mass.

Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway.

Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury.

Microvascular transplantation after acute myocardial infarction.

The primary objective of this study was to evaluate epicardial transplantation of an intact microvascular network for treatment of myocardial ischemia in a murine model of acute myocardial infarction. We describe transplantation of an intact microvascular network constructed from isolated microvascular segments stabilized in a 3-dimensional matrix to the epicardial surface after acute myocardial infarction. This microvascular graft was implanted as a patch on the epicardium of mice after left coronary artery ligation. After 14 and 28 days of implantation, left ventricular (LV) function was assessed and grafts evaluated via histology and cytochemistry. Inosculation of microvessels within the graft with host coronary microcirculation occurred as early as 7 days after initial tissue grafting. Morphologic evaluation of the grafts revealed arterioles, venules, capillaries, and erythrocytes within vascular lumina. Control grafts of collagen alone remained avascular. LV infarct size was smaller, and LV function improved in treated animals. Engraftment of whole microvascular units can be achieved to support cell-assisted vascular remodeling. Microvascular grafts may provide therapeutic benefit as a primary treatment or serve as a microvascular platform for cardiac repair and regeneration.

Vascularization and engraftment of a human skin substitute using circulating progenitor cell-derived endothelial cells.

We seeded tissue engineered human skin substitutes with endothelial cells (EC) differentiated in vitro from progenitors from umbilical cord blood (CB-EC) or adult peripheral blood (AB-EC), comparing the results to previous work using cultured human umbilical vein EC (HUVEC) with or without Bcl-2 transduction. Vascularized skin substitutes were prepared by seeding Bcl-2-transduced or nontransduced HUVEC, CB-EC, or AB-EC on the deep surface of decellularized human dermis following keratinocyte coverage of the epidermal surface. These skin substitutes were transplanted onto C.B-17 SCID/beige mice receiving systemic rapamycin or vehicle control and were analyzed 21 d later. CB-EC and Bcl-2-HUVEC formed more human EC-lined vessels than AB-EC or control HUVEC; CB-EC, Bcl-2-HUVEC, and AB-EC but not control HUVEC promoted ingrowth of mouse EC-lined vessels. Bcl-2 transduction increased the number of human and mouse EC-lined vessels in grafts seeded with HUVEC but not with CB-EC or AB-EC. Both CB-EC and AB-EC-induced microvessels became invested by smooth muscle cell-specific alpha-actin-positive mural cells, indicative of maturation. Rapamycin inhibited ingrowth of mouse EC-lined vessels but did not inhibit formation of human EC-lined vessels. We conclude that EC differentiated from circulating progenitors can be utilized to vascularize human skin substitutes even in the setting of compromised host angiogenesis/vasculogenesis.