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1.
Int J Aging Hum Dev ; 98(2): 135-158, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37337649

RESUMO

This cross-sectional study examined whether internalized age stereotypes mediate the relationship between volunteering and self-efficacy for adults 50+ years of age. A convenience sample of volunteers (n = 173) residing in the United States of America Mountain West completed a 15-min, online survey. The independent variable was number of volunteer hours per week (mean = 6.44, SD = 5.50). The dependent variable was self-efficacy measured by five, four-point items from the general self-efficacy scale (α = .83; mean = 3.57, SD = .38). The indirect effects of five internalized positive and five negative age stereotypes were tested. Results indicate that increased internalized positive, but not negative, age stereotypes partially mediated the relationship between volunteer hours and self-efficacy. Although positive age stereotypes have long been considered a form of ageism, the findings suggest that internalized positive age stereotypes may function as a form of esteem to enhance psychosocial well-being.


Assuntos
Etarismo , Autoeficácia , Humanos , Estados Unidos , Estudos Transversais , Inquéritos e Questionários , Etarismo/psicologia , Voluntários , Estereotipagem , Envelhecimento/psicologia
2.
J Aging Stud ; 67: 101186, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38012946

RESUMO

The aim of this qualitative, phenomenological study was to understand how older adults cope with experiences of ageism and racism through an intersectional lens. Twenty adults 60+ residing in the U.S. Mountain West who identified as Black, Hispanic/Latino(a), Asian-American/Pacific Islander, Indigenous, or White participated individually in a one-hour, semi-structured interview. A team of five coders engaged in an inductive coding process through independent coding followed by critical discussion. Peer debriefing enhanced credibility. Nine themes were organized by three umbrella categories: Coping with ageism: 1) distancing via self-determination/defying stereotypes, 2) distancing by helping others; Coping with racism: 3) resistance, 4) exhaustion; Coping with both ageism and racism: 5) increased awareness through aging, 6) healthy lifestyle, 7) education, 8) acceptance/ 'let it go', and 9) avoidance. Novel findings include how older adults may cope with ageism and racism via increased awareness through aging and with ageism specifically by helping peer older adults, although instances of internalized ageism were noted and discussed. The themes exemplify problem-focused (e.g., helping others) and emotion-focused (acceptance), as well as individual (e.g., self-determination) and collective (e.g., resistance) coping strategies. This study can serve as a resource for practitioners in applying a more nuanced understanding of the ways older adults cope with ageism and racism in later life.


Assuntos
Etarismo , Racismo , Humanos , Idoso , Envelhecimento , Adaptação Psicológica , Pesquisa Qualitativa
3.
J Gerontol B Psychol Sci Soc Sci ; 78(5): 880-890, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-36809313

RESUMO

OBJECTIVES: Ageism is a prevalent, insidious social justice issue that has harmful effects on the health of older adults. Preliminary literature explores the intersectionality of ageism with sexism, ableism, and ageism experienced among LGBTQ+ older adults. Yet, the intersectionality of ageism with racism remains largely absent from the literature. Therefore, this study explores the lived experience of the intersectionality of ageism and racism among older adults. METHODS: This qualitative study applied a phenomenological approach. Twenty participants 60+ years of age (M = 69, standard deviation = 8.84) in the U.S. Mountain West identifying as Black, Latino(a), Asian-American/Pacific Islander, Indigenous, or White engaged in a 1-hr interview between February and July 2021. A 3-cycle coding process applied constant comparison methods. Five coders independently coded interviews, engaging in critical discussion to resolve disagreements. An audit trail, member checking, and peer debriefing enhanced credibility. RESULTS: This study focuses on individual-level experiences exemplified by 3 umbrella themes and 7 subthemes. The subthemes are (a) compounding oppression, (b) intersection of disparities, (c) White privilege, (d) racism and ageism: being tokenized or ignored, (e) ageism and racism: unspoken bias, (f) racism versus ageism: overt or covert? and (g) racism versus ageism: differentiated or ubiquitous? DISCUSSION: The findings indicate how ageism may be racialized through stereotypes related to mental (in)capability. Practitioners can apply the findings to enhance support for older adults by designing interventions aimed at reducing racialized ageist stereotypes and increasing collaboration through education across anti-ageism/anti-racism initiatives. Future research should focus on the impacts of the intersectionality of ageism and racism on specific health outcomes in addition to structural-level interventions.


Assuntos
Etarismo , Racismo , Humanos , Idoso , Discriminação Social
4.
J Soc Issues ; 2022 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-36249546

RESUMO

Intergenerational programs have long been employed to reduce ageism and optimize youth and older adult development. Most involve in-person meetings, which COVID-19 arrested. ​​Needs for safety and social contact were amplified during COVID-19, leading to modified programming that engaged generations remotely rather than eliminating it. Our collective case study incorporates four intergenerational programs in five US states prior to and during COVID-19. Each aims to reduce ageism, incorporating nutrition education, technology skills, or photography programming. Authors present case goals, participants, implementation methods, including responses to COVID-19, outcomes, and lessons learned. Technology afforded opportunities for intergenerational connections; non-technological methods also were employed. Across cases, programmatic foci were maintained through adaptive programming. Community partners' awareness of immediate needs facilitated responsive programming with universities, who leveraged unique resources. While new methods and partnerships will continue post-pandemic, authors concurred that virtual contact cannot fully substitute for in-person relationship-building. Remote programming maintained ties between groups ready to resume shared in-person programming as soon as possible; they now have tested means for responding to routine or novel cancellations of in-person programming. Able to implement in-person and remote intergenerational programming, communities can fight ageism and pursue diverse goals regardless of health, transportation, weather, or other restrictions.

5.
J Aging Stud ; 61: 101031, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35654553

RESUMO

The productive aging literature describes a wide range of psychosocial benefits of volunteerism for older adults. A growing, compelling body of research drawing from stereotype embodiment theory identifies significant, negative public health impacts of internalized age stereotypes. Yet, little research explores which activities may reduce internalized ageism and enhance psychosocial health as people age. This cross-sectional parallel mediation study examines whether internalized age stereotypes mediate the relationship between volunteering and social connectedness for adults over 50. A convenience sample of volunteers (n = 165) 50+ years of age in the U.S. Mountain West completed an online survey primarily during the COVID-19 pandemic. The independent variable is volunteer hours per week (M = 6.45, SD = 5.38). The dependent variable is social connectedness measured by five positively worded items from the UCLA loneliness scale (M = 4.32, SD = 0.63, and α = 0.86). The indirect effects of five internalized positive (e.g., "wise" and "capable") (M = 4.85, SD = 0.68, α = 0.72) and five negative (e.g., "grumpy" and "helpless") (M = 1.20, SD = 1.02, α = 0.74) age stereotypes were tested. Results (n = 154) indicate that increased internalized positive, but not negative, age stereotypes partially mediate the relationship between volunteer hours and increased social connectedness, while holding constant relevant covariates. Although positive age stereotypes have long been considered a form of ageism, the results of this study suggest that internalizing positive age stereotypes may function as a form of esteem (particularly during the pandemic) to promote enhanced psychosocial health as people age.


Assuntos
COVID-19 , Pandemias , Idoso , Estudos Transversais , Humanos , Estereotipagem , Voluntários
6.
J Gerontol Soc Work ; 65(8): 822-831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35272582

RESUMO

The COVID-19 pandemic and associated restrictions pose a significant health threat to older adults. Fear of COVID-19 is associated with increased disease transmission and numerous psychosocial health challenges. While social support has been studied extensively in gerontological literature, there is a gap in understanding how social networks influence fear of COVID-19. This study drew from a convenience sample of 239 adults 60+ years of age in the United States who completed a 20-min survey. Regression results indicate that higher social network was significantly associated with decreased fear of COVID-19. Identifying as female and as an ethnic minority were associated with increased fear of COVID-19. These findings document the need for social workers to promote enhanced social networks in reducing fear of COVID-19 among older adults and attend to disparate levels of fear among older women and people of color.


Assuntos
COVID-19 , Feminino , Estados Unidos/epidemiologia , Humanos , Idoso , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Etnicidade , Grupos Minoritários , Medo , Rede Social
7.
Sci Adv ; 8(2): eabj1570, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35020423

RESUMO

Seedling emergence is critical for food security. It requires rapid hypocotyl elongation and apical hook formation, both of which are mediated by regulated cell expansion. How these events are coordinated in etiolated seedlings is unclear. Here, we show that biphasic control of cell expansion by the phytohormone auxin underlies this process. Shortly after germination, high auxin levels restrain elongation. This provides a temporal window for apical hook formation, involving a gravity-induced auxin maximum on the eventual concave side of the hook. This auxin maximum induces PP2C.D1 expression, leading to asymmetrical H+-ATPase activity across the hypocotyl that contributes to the differential cell elongation underlying hook development. Subsequently, auxin concentrations decline acropetally and switch from restraining to promoting elongation, thereby driving hypocotyl elongation. Our findings demonstrate how differential auxin concentrations throughout the hypocotyl coordinate etiolated development, leading to successful soil emergence.

8.
Int J Aging Hum Dev ; 94(3): 255-272, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34139878

RESUMO

The objective of this study is to test self-efficacy as a mediator in the relationship between three lifestyle activities (exercise, volunteering, and computer use) and self-perceptions of aging (SPA) among older adults. We hypothesize that increased self-efficacy will mediate the relationship between lifestyle activities and more positive SPA. This is a cross-sectional, secondary data analysis drawn from the 2016 wave of the Health and Retirement Study (HRS; n = 4,561). Bootstrapping procedures were applied to test the significance of the indirect effects of self-efficacy in the relationship between lifestyle activities and SPA. Results indicate significant direct effects between exercise, computer use, and self-efficacy. Direct effects were observed between exercise, volunteering, computer use, and SPA. Self-efficacy partially mediated the relationship between exercise, volunteering, computer use, and SPA. Implications for practitioners working with older adults are discussed. Future research should test formal intervention programs aimed at reducing internalized ageism through additional pathways.


Assuntos
Etarismo , Idoso , Envelhecimento , Computadores , Estudos Transversais , Humanos , Estilo de Vida , Autoimagem , Autoeficácia
9.
Health Soc Work ; 45(4): 250-258, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33313779

RESUMO

As a response to our rapidly aging society, professional training programs in health care need to offer rich applied learning experiences with older adults and educate students about ageist attitudes. Health care professionals are likely to work with older adults in a variety of settings, yet ageist attitudes continue to be a barrier to workforce development. This study evaluated the effects of an intergenerational lifelong learning initiative as a way to decrease ageist attitudes in social work students. The research hypothesis was that intergenerational engagement would help reduce ageist attitudes of social work students. Paired samples t tests were conducted with 32 students through pre- and post-surveys of the ROPE (Relating to Old People Evaluation). Results indicated a significant decrease in ageist attitudes overall, in negative ageism, and in students' self-report of behaviors such as complimenting older adults "despite their age" and avoiding older adults. Qualitative comments indicated significant changes in perception about the aging experience and increased awareness of ageist stereotypes. Overall, this pilot study offers an encouraging model that can be applied through future partnerships to reduce ageism of students in health care-related fields.


Assuntos
Envelhecimento , Atitude , Idoso , Humanos , Projetos Piloto , Serviço Social , Estudantes
10.
J Biomech Eng ; 141(12)2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31596925

RESUMO

Ischemic stroke induces rapid loss in bone mineral density that is up to 13 times greater than during normal aging, leading to a markedly increased risk of fracture. Little is known about skeletal changes following stroke beyond density loss. In this study, we use a mild-moderate middle cerebral artery occlusion model to determine the effects of ischemic stroke without bedrest on bone microstructure, dynamic bone formation, and tissue composition. Twenty-seven 12-week-old male C57Bl/6J mice received either a stroke or sham surgery and then either received daily treadmill exercise or remained sedentary for 4 weeks. All mice were ambulatory immediately following stroke, and limb coordination during treadmill exercise was unaffected by stroke, indicating similar mechanical loading across limbs for both stroke and sham groups. Stroke did not directly detriment microstructure, but exercise only stimulated adaptation in the sham group, not the stroke group, with increased bone volume fraction and trabecular thickness in the sham distal femoral metaphysis. Stroke differentially decreased cortical area in the distal femoral metaphysis for the affected limb relative to the unaffected limb, as well as endosteal bone formation rate in the affected tibial diaphysis. Although exercise failed to improve bone microstructure following stroke, exercise increased mineral-to-matrix content in stroke but not sham. Together, these results show that stroke inhibits exercise-induced changes to femoral microstructure but not tibial composition, even without changes to gait. Similarly, affected-unaffected limb differences in cortical bone structure and bone formation rate in ambulatory mice show that stroke affects bone health even without bedrest.

11.
Aerosp Med Hum Perform ; 88(4): 377-384, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28518000

RESUMO

BACKGROUND: Cartilage tissue engineering is a growing field due to the lack of regenerative capacity of native tissue. The use of bioreactors for cartilage tissue engineering is common, but the results are controversial. Some studies suggest that microgravity bioreactors are ideal for chondrogenesis, while others show that mimicking hydrostatic pressure is crucial for cartilage formation. A parallel study comparing the effects of loading and unloading on chondrogenesis has not been performed. METHODS: The goal of this study was to evaluate chondrogenesis of human adipose-derived stem cells (hASC) under two different mechanical stimuli relative to static culture: microgravity and cyclic hydrostatic pressure (CHP). Pellets of hASC were cultured for 14 d under simulated microgravity using a rotating wall vessel bioreactor or under CHP (7.5 MPa, 1 Hz, 4 h · d-1) using a hydrostatic pressure vessel. RESULTS: We found that CHP increased mRNA expression of Aggrecan, Sox9, and Collagen II, caused a threefold increase in sulfated glycosaminoglycan production, and resulted in stronger vimentin staining intensity and organization relative to microgravity. In addition, Wnt-signaling patterns were altered in a manner that suggests that simulated microgravity decreases chondrogenic differentiation when compared to CHP. DISCUSSION: Our goal was to compare chondrogenic differentiation of hASC using a microgravity bioreactor and a hydrostatic pressure vessel, two commonly used bioreactors in cartilage tissue engineering. Our results indicate that CHP promotes hASC chondrogenesis and that microgravity may inhibit hASC chondrogenesis. Our findings further suggest that cartilage formation and regeneration might be compromised in space due to the lack of mechanical loading.Mellor LF, Steward AJ, Nordberg RC, Taylor MA, Loboa EG. Comparison of simulated microgravity and hydrostatic pressure for chondrogenesis of hASC. Aerosp Med Hum Perform. 2017; 88(4):377-384.


Assuntos
Condrogênese/fisiologia , Pressão Hidrostática , Células-Tronco/citologia , Engenharia Tecidual , Simulação de Ausência de Peso , Reatores Biológicos , Técnicas de Cultura de Células , Diferenciação Celular , Humanos , Estimulação Física , Suporte de Carga
12.
Tissue Eng Part A ; 22(15-16): 997-1005, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27392567

RESUMO

Development and maintenance of a vascular network are critical for bone growth and homeostasis; strategies that promote vascular function are critical for clinical success of tissue-engineered bone constructs. Co-culture of endothelial cells (ECs) with mesenchymal stem cells (MSCs) and exposure to 10% cyclic tensile strain have both been shown to regulate osteogenesis in isolation, but potential synergistic effects have yet to be explored. The objective of this study was to expose an MSC-EC co-culture to 10% cyclic tensile strain to examine the role of this mechanical stimulus on MSC-EC behavior. We hypothesized that paracrine signaling from ECs would stimulate osteogenesis of MSCs, and exposure to 10% cyclic tensile strain would enhance this anabolic signal. Human umbilical vein ECs and human bone marrow-derived MSCs were either monocultured or co-cultured at a 1:1 ratio in a mixed osteo/angiogenic medium, exposed to 10% cyclic tensile strain at 1 Hz for 4 h/day for 2 weeks, and biochemically and histologically analyzed for endothelial and osteogenic markers. While neither 10% cyclic tensile strain nor co-culture alone had a significant effect on osteogenesis, the concurrent application of strain to an MSC-EC co-culture resulted in a significant increase in calcium accretion and mineral deposition, suggesting that co-culture and strain synergistically enhance osteogenesis. Neither co-culture, 10% cyclic tensile strain, nor a combination of these stimuli affected endothelial markers, indicating that the endothelial phenotype remained stable, but unresponsive to the stimuli evaluated in this study. This study is the first to investigate the role of cyclic tensile strain on the complex interplay between ECs and MSCs in co-culture. The results of this study provide key insights into the synergistic effects of 10% cyclic tensile strain and co-culture on osteogenesis. Understanding mechanobiological factors affecting MSC-EC crosstalk will help enhance strategies for creating vascularized tissues in tissue engineering and regenerative medicine.


Assuntos
Antígenos de Diferenciação/biossíntese , Células Endoteliais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica , Osteogênese , Adolescente , Adulto , Técnicas de Cocultura , Células Endoteliais/citologia , Feminino , Humanos , Células-Tronco Mesenquimais/citologia
13.
Tissue Eng Part A ; 22(11-12): 831-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27137792

RESUMO

Although hydrostatic pressure (HP) is known to regulate chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs), improved insight into the mechanotransduction of HP may form the basis for novel tissue engineering strategies. Previously, we demonstrated that matrix stiffness and calcium ion (Ca(++)) mobility regulate the mechanotransduction of HP; however, the mechanisms, by which these Ca(++) signaling pathways are initiated, are currently unknown. The purinergic pathway, in which adenosine triphosphate (ATP) is released and activates P-receptors to initiate Ca(++) signaling, plays a key role in the mechanotransduction of compression, but has yet to be investigated with regard to HP. Therefore, the objective of this study was to investigate the interplay between purinergic signaling, matrix stiffness, and the chondrogenic response of MSCs to HP. Porcine bone marrow-derived MSCs were seeded into soft or stiff agarose hydrogels and subjected to HP (10 MPa at 1 Hz for 4 h/d for 21 days) or kept in free swelling conditions. Stiff constructs were incubated with pharmacological inhibitors of extracellular ATP, P2 receptors, or hemichannels, or without any inhibitors as a control. As with other loading modalities, HP significantly increased ATP release in the control group; however, inhibition of hemichannels completely abrogated this response. The increase in sulfated glycosaminoglycan (sGAG) synthesis and vimentin reorganization observed in the control group in response to HP was suppressed in the presence of all three inhibitors, suggesting that purinergic signaling is involved in the mechanoresponse of MSCs to HP. Interestingly, ATP was released from both soft and stiff hydrogels in response to HP, but HP only enhanced chondrogenesis in the stiff hydrogels, indicating that matrix stiffness may act downstream of purinergic signaling to regulate the mechanoresponse of MSCs to HP. Addition of exogenous ATP did not replicate the effects of HP on chondrogenesis, suggesting that mechanisms other than purinergic signaling also regulate the response of MSCs to HP.


Assuntos
Condrogênese/efeitos dos fármacos , Pressão Hidrostática , Células-Tronco Mesenquimais/citologia , Receptores Purinérgicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta3/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Células Cultivadas , Matriz Extracelular/metabolismo , Mecanotransdução Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Modelos Biológicos , Sus scrofa , Vimentina/metabolismo
14.
J Anat ; 227(6): 717-31, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25382217

RESUMO

Biophysical cues play a key role in directing the lineage commitment of mesenchymal stem cells or multipotent stromal cells (MSCs), but the mechanotransductive mechanisms at play are still not fully understood. This review article first describes the roles of both substrate mechanics (e.g. stiffness and topography) and extrinsic mechanical cues (e.g. fluid flow, compression, hydrostatic pressure, tension) on the differentiation of MSCs. A specific focus is placed on the role of such factors in regulating the osteogenic, chondrogenic, myogenic and adipogenic differentiation of MSCs. Next, the article focuses on the cellular components, specifically integrins, ion channels, focal adhesions and the cytoskeleton, hypothesized to be involved in MSC mechanotransduction. This review aims to illustrate the strides that have been made in elucidating how MSCs sense and respond to their mechanical environment, and also to identify areas where further research is needed.


Assuntos
Mecanotransdução Celular/fisiologia , Células-Tronco Mesenquimais/fisiologia , Adipogenia/fisiologia , Forma Celular , Condrogênese/fisiologia , Citoesqueleto/fisiologia , Módulo de Elasticidade , Matriz Extracelular/fisiologia , Humanos , Integrinas/fisiologia , Canais Iônicos/fisiologia , Desenvolvimento Muscular/fisiologia , Osteogênese/fisiologia
15.
J Mech Behav Biomed Mater ; 38: 174-82, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24054946

RESUMO

The objective of this study was to explore how the response of mesenchymal stem cells (MSCs) to dynamic compression (DC) depends on their pericellular environment and the development of their cytoskeleton. MSCs were first seeded into 3% agarose hydrogels, stimulated with the chondrogenic growth factor TGF-ß3 and exposed to DC (~10% strain at 1Hz) for 1h on either day 7, 14, or 21 of culture. At each time point, the actin, vimentin and tubulin networks of the MSCs were assessed using confocal microscopy. Similar to previous results, MSCs displayed a temporal response to DC; however, no dramatic changes in gross cytoskeletal organization were observed with time in culture. Vinculin (a membrane-cytoskeletal protein in focal adhesions) staining appeared more intense with time in culture. We next aimed to explore how changes to the pericellular environment, independent of the duration of exposure to TGF-ß3, would influence the response of MSCs to DC. To this end, MSCs were encapsulated into either 'soft' or 'stiff' agarose hydrogels that are known to differentially support pericellular matrix (PCM) development. The application of DC led to greater relative increases in the expression of chondrogenic marker genes in the stiffer hydrogels, where the MSCs were found to have a more well developed PCM. These increases in gene expression were not observed following the addition of RGDS, an integrin blocker, suggesting that integrin binding plays a role in determining the response of MSCs to DC. Microtubule organization in MSCs was found to adapt in response to DC, but this effect was not integrin mediated, as this cytoskeletal reorganization was also observed in the presence of RGDS. In conclusion, although the PCM, integrin binding, and cytoskeletal reorganization are all involved in mechanotransduction of DC, none of these factors in isolation was able to completely explain the temporal mechanosensitivity of MSCs to dynamic compression.


Assuntos
Força Compressiva , Citoesqueleto/efeitos dos fármacos , Hidrogéis/farmacologia , Integrinas/metabolismo , Mecanotransdução Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Actinas/metabolismo , Animais , Condrogênese/efeitos dos fármacos , Citoesqueleto/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Microtúbulos/metabolismo , Ligação Proteica/efeitos dos fármacos , Suínos , Fatores de Tempo , Tubulina (Proteína)/metabolismo , Vimentina/metabolismo , Suporte de Carga
16.
J Biomech ; 45(15): 2483-92, 2012 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-22925995

RESUMO

The aim of this study was to explore how cell-matrix interactions and extrinsic mechanical signals interact to determine stem cell fate in response to transforming growth factor-ß3 (TGF-ß3). Bone marrow derived mesenchymal stem cells (MSCs) were seeded in agarose and fibrin hydrogels and subjected to dynamic compression in the presence of different concentrations of TGF-ß3. Markers of chondrogenic, myogenic and endochondral differentiation were assessed. MSCs embedded within agarose hydrogels adopted a spherical cell morphology, while cells directly adhered to the fibrin matrix and took on a spread morphology. Free-swelling agarose constructs stained positively for chondrogenic markers, with MSCs appearing to progress towards terminal differentiation as indicated by mineral staining. MSC seeded fibrin constructs progressed along an alternative myogenic pathway in long-term free-swelling culture. Dynamic compression suppressed differentiation towards any investigated lineage in both fibrin and agarose hydrogels in the short-term. Given that fibrin clots have been shown to support a chondrogenic phenotype in vivo within mechanically loaded joint defect environments, we next explored the influence of long term (42 days) dynamic compression on MSC differentiation. Mechanical signals generated by this extrinsic loading ultimately governed MSC fate, directing MSCs along a chondrogenic pathway as opposed to the default myogenic phenotype supported within unloaded fibrin clots. In conclusion, this study demonstrates that external cues such as the mechanical environment can override the influence specific substrates, scaffolds or hydrogels have on determining mesenchymal stem cell fate. The temporal data presented in this study highlights the importance of considering how MSCs respond to extrinsic mechanical signals in the long term.


Assuntos
Distinções e Prêmios , Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Condrogênese , Fibrina/química , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrogéis/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Desenvolvimento Muscular , Sefarose/química , Estresse Mecânico , Suínos , Fator de Crescimento Transformador beta3/farmacologia
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