Integration of Advance Care Planning Into Clinical Practice: A Quality Improvement Project for Leaders.

OBJECTIVE: This quality improvement initiative sought to develop a proactive integrated system approach to advance care planning (ACP) through leadership and colleague engagement. BACKGROUND: Nurse leaders have the capacity to influence the professional competencies of care teams in ACP. Nurse leaders were educated on the importance of ACP, national quality metrics, resources for staff education, and ways to integrate ACP into workflows based on a population management model. METHODS: The project design is a prospective, mixed method design. RESULTS: Nurse leader participants demonstrated a significant increase in knowledge of the importance of ACP and evidence-based models to increase staff engagement and competency. CONCLUSIONS: Study supports nurse leader interventions, promoted engagement of proactive ACP to honor patient choice, and aligns with the mission and vision of one of the largest national Catholic healthcare organizations of being a trusted partner for life.

Human primitive mesenchymal stem cell-derived retinal progenitor cells improved neuroprotection, neurogenesis, and vision in rd12 mouse model of retinitis pigmentosa.

BACKGROUND: Currently, there is no treatment for retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP). Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. Thus far, primarily adult mesenchymal stem cells (MSCs) have been investigated in preclinical and clinical studies, and the results have not been convincing. We applied a new approach in which primitive (p) MSC-derived retinal progenitor cells (RPCs) were examined to treat retinal degeneration in an rd12 mouse model of RP. METHODS: Well-characterized pMSCs and RPCs labeled with PKH26 were intravitreally injected into rd12 mice. The vision and retinal function of transplanted animals were analyzed using electroretinography. Animals were killed 4 and 8 weeks after cell transplantation for histological, immunological, molecular, and transcriptomic analyses of the retina. RESULTS: Transplanted RPCs significantly improved vision and retinal thickness as well as function in rd12 mice. pMSCs and RPCs homed to distinct retinal layers. pMSCs homed to the retinal pigment epithelium, and RPCs migrated to the neural layers of the retina, where they improved the thickness of the respective layers and expressed cell-specific markers. RPCs induced anti-inflammatory and neuroprotective responses as well as upregulated the expression of genes involved in neurogenesis. The transcriptomic analysis showed that RPCs promoted neurogenesis and functional recovery of the retina through inhibition of BMP and activation of JAK/STAT and MAPK signaling pathways. CONCLUSIONS: Our study demonstrated that RPCs countered inflammation, provided retinal protection, and promoted neurogenesis resulting in improved retinal structure and physiological function in rd12 mice.

In vivo intervertebral disc regeneration using stem cell-derived chondroprogenitors.

OBJECT: There is currently no biologic therapy to repair or restore a degenerated intervertebral disc. A potential solution may rest with embryonic stem cells (ESCs), which have a potential to grow indefinitely and differentiate into a variety of cell types in vitro. Prior studies have shown that ESCs can be encouraged to differentiate toward specific cell lineages by culture in selective media and specific growth environment. Among these lineages, there are cells capable of potentially producing nucleus pulposus (NP) in vivo. In this investigation, the authors studied ESCderived chondroprogenitors implanted into a degenerated disc in a rabbit. For this purpose, a rabbit model of disc degeneration was developed. METHODS: A percutaneous animal model of disc degeneration was developed by needle puncture of healthy intact discs in 16 New Zealand white rabbits. Series of spine MR imaging studies were obtained before disc puncture and after 2, 6, and 8 weeks. Prior to implantation, murine ESCs were cultured with cis-retinoic acid, transforming growth factor beta, ascorbic acid, and insulin-like growth factor to induce differentiation toward a chondrocyte lineage. After confirmation by MR imaging, degenerated disc levels were injected with chondrogenic derivatives of ESCs expressing green fluorescent protein. At 8 weeks post-ESC implantation, the animals were killed and the intervertebral discs were harvested and analyzed using H & E staining, confocal fluorescent microscopy, and immunohistochemical analysis. Three intervertebral disc groups were analyzed in 16 rabbits, as follows: 1) Group A, control: naïve, nonpunctured discs (32 discs, levels L4-5 and L5-6); 2) Group B, experimental control: punctured disc (16 discs, level L2-3); and 3) Group C, experimental: punctured disc followed by implantation of chondroprogenitor cells (16 discs, level L3-4). RESULTS: The MR imaging studies confirmed intervertebral disc degeneration at needle-punctured segments starting at approximately 2 weeks. Postmortem H & E histological analysis of Group A discs showed mature chondrocytes and no notochordal cells. Group B discs displayed an intact anulus fibrosus and generalized disorganization within fibrous tissue of NP. Group C discs showed islands of notochordal cell growth. Immunofluorescent staining for notochordal cells was negative for Groups A and B but revealed viable notochordal-type cells within experimental Group C discs, which had been implanted with ESC derivatives. Notably, no inflammatory response was noted in Group C discs. CONCLUSIONS: This study illustrates a reproducible percutaneous model for studying disc degeneration. New notochordal cell populations were seen in degenerated discs injected with ESCs. The lack of immune response to a xenograft of mouse cells in an immunocompetent rabbit model may suggest an as yet unrecognized immunoprivileged site within the intervertebral disc space.

Mesenchymal stem cells: Cell therapy and regeneration potential.

Rapid advances in the isolation of multipotent progenitor cells, routinely called mesenchymal stromal/stem cells (MSCs), from various human tissues and organs have provided impetus to the field of cell therapy and regenerative medicine. The most widely studied sources of MSCs include bone marrow, adipose, muscle, peripheral blood, umbilical cord, placenta, fetal tissue, and amniotic fluid. According to the standard definition of MSCs, these clonal cells adhere to plastic, express cluster of differentiation (CD) markers such as CD73, CD90, and CD105 markers, and can differentiate into adipogenic, chondrogenic, and osteogenic lineages in vitro. However, isolated MSCs have been reported to vary in their potency and self-renewal potential. As a result, the MSCs used for clinical applications often lead to variable or even conflicting results. The lack of uniform characterization methods both in vitro and in vivo also contributes to this confusion. Therefore, the name "MSCs" itself has been increasingly questioned lately. As the use of MSCs is expanding rapidly, there is an increasing need to understand the potential sources and specific potencies of MSCs. This review discusses and compares the characteristics of MSCs and suggests that the variations in their distinctive features are dependent on the source and method of isolation as well as epigenetic changes during maintenance and growth. We also discuss the potential opportunities and challenges of MSC research with the hope to stimulate their use for therapeutic and regenerative medicine.

Implications of Serum 25-Hydroxyvitamin D on the Prevalence of Neoplastic Polyps: A Cross-Sectional Study.

BACKGROUND: Vitamin D is believed to help in the suppression of malignant cells. Epidemiologic studies suggest that there is an association between vitamin D deficiency and an increased risk of colorectal cancer. The primary aim of this study is to determine if the prevalence of neoplastic polyps is inversely related to serum 25-hydroxyvitamin D levels 25(OH)D. METHODS: A prevalence study conducted between April 2009 and October 2009 evaluated 651 patients undergoing colonoscopy in order to determine if an association existed between low 25(OH)D levels and the prevalence of neoplastic colon polyps. Multivariate logistic and linear regression analyses were used to establish an association between 25(OH)D levels and histology of colon polyp with gender, race, age and BMI. RESULTS: The presence of tubular adenoma, villous adenoma, tubulo-villous adenoma, or malignancies did not differ (P = 0.5) among the stratified 25(OH)D groups (10 ng, 10.1 - 30 ng, > 30 ng). In addition, despite having more African-Americans than Caucasians in the lowest 25(OH)D category (22.7% versus 7.7%), the presence of neoplastic polyps did not differ significantly (P = 0.8) between the categorized racial groups (Caucasian and African-Americans). CONCLUSIONS: Low plasma 25(OH)D levels are not associated with an increased prevalence of neoplastic polyps.

Chondrogenic derivatives of embryonic stem cells seeded into 3D polycaprolactone scaffolds generated cartilage tissue in vivo.

In spite of recent scientific advances, treatment and repair of cartilage using tissue engineering techniques remains challenging. The major constraint is the limited proliferative capacity of mature autologous chondrocytes used in the tissue engineering approach. This problem can be addressed by using stem cells, which can self-renew with greater proliferative potential. Cartilage tissue engineering using adult mesenchymal stem cells derived from bone marrows has met with limited success. In this study we explored cartilage tissue generation from embryonic stem cells (ESCs). ESCs were induced to differentiate into chondroprogenitors, capable of proliferating and subsequently differentiating into cartilage-producing cells. The chondrogenic cells expressed chondrocyte-specific markers and deposited extracellular matrix proteins, proteoglycans. ESC-derived chondrogenic cells and polycaprolactone scaffolds seeded with these cells implanted in mice (129 SvImJ) generated cartilage tissue in vivo. Postimplant analysis of the retrieved tissues demonstrated cartilage-like tissue formation in 3-4 weeks. The cells of retrieved tissues also expressed the chondrocyte-specific marker collagen II. These findings suggest that ESCs can be used for tissue engineering and cultivation of cartilage tissues.

Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels.

BACKGROUND: Although paternal alcohol exposure has been shown to affect the growth and behavior of offspring, the mechanisms underlying these effects still remain to be elucidated. This study examines one possible mechanism, namely, altered genomic imprinting as reflected by changes in sperm cytosine methyltransferase messenger RNA (mRNA) levels. METHODS: Male rats were treated with alcohol for 9 weeks before breeding. Resulting fetuses were counted and weighed, and paternal sperm was examined for changes in cytosine methyltransferase mRNA levels. RESULTS: Alcohol did not affect mating, fecundity, or litter size, but it did result in significantly decreased mean fetal weight, increased fetal runt incidence in offspring, and decreased cytosine methyltransferase mRNA levels in paternal sperm, compared with pair-fed and ad libitum controls. CONCLUSIONS: Alcohol-induced reductions in cytosine methyltransferase mRNA levels may reflect altered genomic imprinting caused by reduced DNA methylation, which, in turn, may lead to the expression of normally silent paternal alleles and may be a mechanism for paternal alcohol effects.