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OBJECTIVES: To report the UK experience of rolling out Transfusion Camp. BACKGROUND: Transfusion Camp is a structured education programme developed in Toronto, with the aim of reducing knowledge gaps in transfusion medicine in postgraduate trainees. It consists of didactic lectures viewed online by the participants, then interactive, locally delivered seminars. Since 2015, it has been rolled out in the United Kingdom, and is now available in four centres. Here, we report the UK experience of Transfusion Camp and outcomes. METHODS: Trainees are recruited via the training programme directors in each region. Pre- and post-course assessments are administered using the validated BEST (Biomedical Excellence for Safer Transfusion) test, with possible scores 0-20, and confidence measured on an A-E Likert scale. RESULTS: Since 2015, 130 trainees have participated in Transfusion Camp in the United Kingdom. Trainees from all specialties significantly improved their BEST-test scores after attending the course (mean score 11.6/20 before the course, compared with 14.3/20 after the course), and confidence in managing transfusion-related issues was also significantly improved. CONCLUSION: We recommend that all centres consider offering Transfusion Camp to trainees in haematology and other specialties that frequently use blood transfusions, such as anaesthesia/ICU, Internal Medicine and others.
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BACKGROUND: Studies have described poor transfusion medicine (TM) knowledge in postgraduate trainees. The impact of undergraduate medical TM education on postgraduate knowledge is unclear. METHODS: Canadian medical schools were surveyed on the number of hours dedicated to TM teaching and topics covered by curricula during 2016-2020. Postgraduate trainees attending Transfusion Camp in 2021 completed a pretest of 20 multiple-choice questions. The survey results and pretest scores were compared to evaluate the association between undergraduate medical TM education and pretest scores. RESULTS: The survey was completed by 16 of 17 Canadian medical schools. The number of hours (h) of TM teaching were <2 h (25%), 3-4 h (25%), and >4 h (50%). Twelve of 19 Transfusion Camp topics were covered in ≥50% of schools. Eleven medical schools provided ethics approvals/waivers to include trainee pretest scores in the analysis (N = 200). The median pretest scores by medical school ranged from 48% to 70%. No association was found between number of TM teaching hours and average pretest scores (p = .60). There was an association between higher postgraduate year level and individual pretest score (p < .0001). The analysis by topic demonstrated questions where trainees from different schools performed uniformly well or poorly; other topics showed considerable variation. CONCLUSION: Variation in quantity and content of undergraduate TM teaching exists across Canadian medical schools. In this limited assessment, the number of TM teaching hours was not associated with performance on the pretest. This study raises the opportunity to re-evaluate the delivery (content, timing, consistency) of TM education in undergraduate medical schools.
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Curriculum , Educación de Pregrado en Medicina , Medicina Transfusional , Humanos , Medicina Transfusional/educación , Educación de Pregrado en Medicina/métodos , Canadá , Encuestas y Cuestionarios , Facultades de Medicina , Masculino , Femenino , Competencia ClínicaRESUMEN
BACKGROUND AND OBJECTIVES: Blood transfusion is performed daily in hospitals. Gaps exist between transfusion guidelines and day-to-day clinical care. These gaps are prevalent in resource-limited settings due to scarce continuing medical education. Transfusion Camp Rwanda aims to bridge this gap by (1) delivering context-appropriate up-to-date education, (2) teaching participants how to independently deliver a case-based curriculum and (3) identifying strategies to promote change in transfusion practice in Rwanda. MATERIALS AND METHODS: In May 2023, a multidisciplinary team from Canada and Rwanda carried out a Transfusion Camp train-the-trainer workshop for clinicians from all five provinces in Rwanda. Participants attended in-person lectures, seminars and workshop group discussions on the implementation of the Rwanda National Directives on Rational Use of Blood and Blood Components. Course feedback was based on the Kirkpatrick Model of Training and Evaluation. RESULTS: Fifty-one physicians and laboratory technicians participated in the course. Confidence in caring for patients based on transfusion guidelines was self-rated as 'excellent' by 23% of participants before and 77% after, while 84% reported they planned to teach Transfusion Camp to others and 100% responded that they will apply course content to clinical practice. Workshop groups recommended strategies to improve transfusion medicine practice in Rwanda in four domains: Communication, Institutional Approval, Practice Audits and Education. CONCLUSION: Transfusion medicine education in Rwanda using a train-the-trainer approach was well-received by participants and allowed for a more detailed understanding of the local medical and educational environment. These observations can inform the further expansion of the Transfusion Camp Rwanda project.
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Transfusión Sanguínea , Medicina Transfusional , Rwanda , Humanos , Medicina Transfusional/educación , Investigación Biomédica Traslacional/educación , Educación Médica Continua/métodos , Liderazgo , Femenino , Masculino , CurriculumRESUMEN
BACKGROUND: Safe blood transfusion is an increasing priority in global health equity. The Global Health 2030 commission lists access to a safe blood supply as essential for all surgical and nonoperative patients. The objective of this study was to determine if Transfusion Camp, when modified through a collaborative partnership between experts in Canada and Rwanda, results in improved knowledge and confidence among trainees in a resource-limited setting in sub-Saharan Africa. METHODS: This prospective study took place at The University Teaching Hospital of Kigali in Rwanda. Participants were postgraduate medical trainees from departments where blood transfusion is frequent. Participants watched five prerecorded lectures and then attended a 5-hour team-based learning seminar to consolidate learning. Pre- and post-data were analyzed on transfusion knowledge and trainee confidence. A Rasch analysis investigated the performance of individual questions in assessing respondent knowledge. RESULTS: Of 31 trainees from surgery, anesthesia, internal medicine, and pediatrics invited to the course, 27 trainees attended the in-person team-based learning and 24 trainees completed the pre- and post-course analysis. Trainee knowledge assessment improved from (mean ± SD) 7.7/20 ± 1.95 to 10.4/20 ± 2.4 (p < .0001) and this knowledge was maintained by 12 trainees on a 3-month follow-up with a mean score of 9.3/20 ± 2.3. Trainees reported increased confidence in managing transfusion medicine-related patient issues. CONCLUSION: This pilot study demonstrated that Transfusion Camp education content modified to the local context can result in increased knowledge and confidence in managing transfusion-related issues. These results will inform future planning of Transfusion Camp in resource-limited settings.
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Transfusión Sanguínea , Competencia Clínica , Humanos , Niño , Estudios Prospectivos , Rwanda , Proyectos Piloto , Estudios de FactibilidadRESUMEN
BACKGROUND: Due to few teaching faculty, resource-limited settings may lack the education curricula providers need for safe practice. As safe surgery becomes an increasing priority worldwide, it is essential to improve access to critical education content including in transfusion medicine. Transfusion Camp is a longitudinal curriculum, shown to increase knowledge in postgraduate trainees. The objective was to develop a sustainable bilateral partnership between Rwanda and Canada, and to integrate Transfusion Camp into the existing curriculum of the School of Medicine and Pharmacy at University of Rwanda. METHODS: A Transfusion Camp pilot course was initiated through collaboration of experts in Rwanda and Canada. Planning occurred over 6 months via online and in-person meetings. Canadian teaching faculty adapted course content via iterative discussion with Rwandan faculty. Final content was delivered through online pre-recorded lectures by Canadian Faculty, and in-person small-group seminars by Rwandan Faculty. Project feasibility was assessed through structured evaluation and informal debriefing. RESULTS: Twenty-seven postgraduate trainees were present for the pilot course, of whom 21 (78%) submitted evaluation forms. While the structure and content of the adapted Transfusion Camp curriculum were well-received, the majority of respondents indicated a preference for in-person rather than pre-recorded lectures. Debriefing determined that future courses should focus on continuing education initiatives aimed at physicians entering or already in independent practice. CONCLUSION: A partnership between universities and blood operators in high-resource and resource-limited countries results in a transfusion medicine curriculum that is locally applicable, multidisciplinary, and supportive of learning benefitting the learners and educators alike.
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Medicina Transfusional , Humanos , Medicina Transfusional/educación , Rwanda , Configuración de Recursos Limitados , Canadá , CurriculumRESUMEN
BACKGROUND: The optimal method of postgraduate transfusion medicine (TM) education remains understudied. One novel approach is Transfusion Camp, a longitudinal 5-day program that delivers TM education to Canadian and international trainees. The purpose of this study was to determine the self-reported impact of Transfusion Camp on trainee clinical practice. STUDY DESIGN AND METHODS: A retrospective analysis of anonymous survey evaluations from Transfusion Camp trainees over three academic years (2018-2021) was conducted. Trainees were asked, "Have you applied any of your learning from Transfusion Camp into your clinical practice?". Through an iterative process, responses were categorized into topics according to program learning objectives. The primary outcome was the rate of self-reported impact of Transfusion Camp on clinical practice. Secondary outcomes were to determine impact based on specialty and postgraduate year (PGY). RESULTS: Survey response rate was 22%-32% over three academic years. Of 757 survey responses, 68% of respondents indicated that Transfusion Camp had an impact on their practice, increasing to 83% on day 5. The most frequent areas of impact included transfusion indications (45%) and transfusion risk management (27%). Impact increased as PGY increased with 75% of PGY-4+ trainees reporting impact. In multivariable analysis, the impact of specialty and PGY varied depending on the objective. DISCUSSION: The majority of trainees report applying learnings from Transfusion Camp to their clinical practice with variations based on PGY and specialty. These findings support Transfusion Camp as an effective means of TM education and help identify high-yield areas and gaps for future curriculum planning.
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Internado y Residencia , Humanos , Autoinforme , Estudios Retrospectivos , Canadá , Educación de Postgrado en Medicina , Curriculum , Competencia ClínicaRESUMEN
BACKGROUND: Blood transfusion is common and potentially lifesaving but is associated with risk and overuse. Nurse practitioners (NPs) in multidisciplinary care teams are increasingly expanding their scope of practice to transfusion medicine (TM). Resources aimed at NPs are lacking, and little is known about NP TM knowledge. Thus, we developed a pilot TM curriculum for NP credentialing and assessed its impact. METHODS: NP leads and TM directors adapted the successful Canadian Transfusion Camp for medical postgraduate trainees into a 3-day curriculum for NPs. Two modalities were used to assess the pilot: 1) a participant demographics survey and needs assessment; and 2) the validated BEST-TEST knowledge assessment exam administered before and after the course. RESULTS: Of the 23 volunteer participants, the majority reported prescribing blood products within the last year, primarily red blood cells. Minimal opportunities to undertake continuing medical education in TM were identified. NPs often used preprinted order forms, consultation with physicians sharing care, or local fact sheets to guide transfusion; rather than TM physician consultation or guidelines. Exam scores significantly improved after the course (before, 35.2% vs. after, 50.3%; p = 0.005), suggesting average initial knowledge being below medical postgraduate trainee-level improving to postgraduate trainee level. Questions on appropriate transfusion triggers and correct recipient identification were most correctly answered; and responses to transfusion reaction questions required improvement. CONCLUSIONS: Our needs assessment suggests that TM resources for NPs are relevant but lacking. Our initiative supports the generalizability, scalability, and effectiveness of the Transfusion Camp program. Further implementation, refinement, and future impact assessments are required.
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Curriculum , Educación Médica Continua , Enfermeras Practicantes/educación , Medicina Transfusional/educación , Canadá , Humanos , Proyectos PilotoRESUMEN
BACKGROUND: The optimal method of providing transfusion medicine (TM) education has not been determined. Transfusion Camp was established in 2012 at the University of Toronto as a centrally delivered TM education program for postgraduate trainees. The impact of Transfusion Camp on knowledge, attitudes, and self-reported behavior was evaluated. METHODS: Didactic lectures (delivered locally, by webinar, or recorded) and locally facilitated team-based learning seminars were delivered over 5 days during the academic year to 8 sites: 7 in Canada and 1 in the United Kingdom. Knowledge assessment using a validated 20-question multiple-choice exam was conducted before and after Transfusion Camp. Attitudes and self-reported behavior were collected through a survey. RESULTS: Over 2 academic years (July 2016 to June 2018), 390 trainees from 16 different specialties (predominantly anesthesia, 41%; hematology, 14%; and critical care, 7%) attended at least 1 day of Transfusion Camp. The mean pretest score was 10.3 of 20 (±2.9; n = 286) compared with posttest score of 13.0 (±2.8; n = 194; p < 0.0001). Lower pretest score and greater attendance (4-5 days compared with 1-3 days) were associated with larger improvement in posttest score; delivery format, specialty, and postgraduate year were not. Trainees reported an improvement in self-rated abilities to manage TM scenarios; 95% rated TM knowledge as very or extremely important in providing patient care; and 81% indicated that they had applied learning from Transfusion Camp into clinical practice. CONCLUSIONS: Transfusion Camp increased TM knowledge, fostered a positive attitude toward TM, and enabled a self-reported positive impact on transfusion practice in postgraduate trainees. It is a novel and scalable approach to delivering TM education.
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Transfusión Sanguínea , Curriculum , Hematología/educación , Internado y Residencia/métodos , Medicina Transfusional/educación , Actitud , Transfusión Sanguínea/métodos , Transfusión Sanguínea/normas , Canadá , Curriculum/normas , Conocimientos, Actitudes y Práctica en Salud , Humanos , Internado y Residencia/organización & administración , Medicina , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Autoinforme , Estudiantes de Medicina/psicologíaRESUMEN
BACKGROUND: Research is needed to enhance cord blood (CB) transplantation outcomes and to develop new clinical applications. Based on quality criteria for transplantation, CB collected by public CB banks (CBBs) is often unsuitable for banking, but may still be valuable for research. Canadian researchers have described a need for a centralized program providing ethically sourced CB for research projects. To meet this need, Canadian Blood Services (CBS), in partnership with The Ottawa Hospital, launched the Cord Blood for Research Program (CBRP) in 2014. STUDY DESIGN AND METHODS: The CBRP developed processes for donor research consent and research project approval with oversight from CBS's CBB and appropriate research ethics boards. The CBRP distributes deidentified CB products to research projects across Canada. RESULTS: Since its inception, the CBRP has distributed more than 525 CB units to researchers, supporting 11 research projects. Of the mothers who donate their baby's CB, 77% have chosen to consent to its use for research if it is not bankable. The number of CB units currently available for research via the CBRP exceeds the requests from researchers. CONCLUSION: The CBRP reliably distributes quality CB products that do not qualify for banking to investigators across Canada in an ethical, legal, and transparent manner. This provides an opportunity for the public to directly support research, helps meet the need expressed by Canada's research community, and maximizes the donor's gift. More research is needed to clarify the factors influencing donor and researcher participation in the CBRP.
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Bancos de Sangre , Sangre Fetal , Investigación , Canadá , HumanosRESUMEN
In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS-in collaboration with researchers from the Stem Cell Network-have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.
En 2013, la Société canadienne du sang (SCS) a lancé la Banque publique nationale de sang de cordon ombilical (BPNSCO) : un programme de prélèvement, de traitement, d'analyse et d'entreposage d'unités de sang de cordon ombilical ayant fait l'objet d'un don pour une utilisation dans le cadre de greffes. La mise sur pied d'un programme permettant l'utilisation, aux fins de la recherche biomédicale, du sang de cordon ombilical ne pouvant être mis en banque ni être utilisé pour des greffes constitue une composante clé de la création de la BPNSCO. Conjointement avec l'élaboration de processus et de politiques permettant la gestion de la BPNSCO et du programme de recherche sur le sang de cordon ombilical, la SCS (en collaboration avec les chercheurs du Réseau de cellules souches) ont également conçu des outils pédagogiques permettant l'offre de renseignements pertinents aux populations visées, de façon à faciliter la mise en Åuvre et la gestion des activités. Nous décrivons ici l'un de ces outils : le REB Primer on Research and Cord Blood Donation (le « guide ¼). Ce « guide ¼ souligne les enjeux éthiques et légaux clés, et identifie les documents canadiens pertinents en ce qui concerne l'utilisation de sang de cordon ombilical aux fins de la recherche biomédicale. Ce « guide ¼ présente également la BPNSCO et décrit les systèmes qui sont mis en Åuvre par la SCS pour répondre aux questions éthiques. Il a pour but d'aider les conseils d'éthique de la recherche à évaluer l'acceptabilité éthique des protocoles de recherche, de faciliter l'harmonisation des processus décisionnels en offrant un cadre de référence commun et de souligner le rôle des conseils d'éthique de la recherche dans les cadres de gouvernance. Grâce à ce « guide ¼, nous espérons illustrer la façon dont l'élaboration de tels outils pédagogiques peut faciliter la mise en Åuvre et la gestion éthiques de programmes associés à la recherche sur les cellules souches au Canada et à l'étranger.
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Investigación Biomédica , Bancos de Sangre/organización & administración , Sangre Fetal , Educación en Salud/organización & administración , Donantes de Sangre , Canadá , Ética en Investigación , HumanosRESUMEN
Considerable progress has been made in recent years in understanding platelet biology and in strengthening the clinical evidence base around platelet transfusion thresholds and appropriate platelet dosing. Platelet alloimmunization rates have also declined. Nevertheless, controversies and uncertainties remain that are relevant to how these products can best be used for the benefit of platelet transfusion recipients. Platelets are unique among the blood products directly derived from whole blood or apheresis donations in requiring storage, with shaking, at ambient temperature. Storage is accordingly constrained between the need to limit the growth of any microbes in the product and the need to minimize losses in platelet function associated with storage. Proteomic and genomic approaches are being applied to the platelet storage lesion. Platelet inventory management is made challenging by these constraints. Although bacterial screening has enhanced the safety of platelet transfusions, pathogen reduction technology may offer further benefits. Continuing clinical investigations are warranted to understand the value of transfusing platelets prophylactically or only in response to bleeding in different patient groups and how best to manage the most grievously injured trauma patients. Patients refractory to platelet transfusions also require expert clinical management. The engineering of platelet substitute products is an active area of research, but considerable hurdles remain before any clinical uses may be contemplated. Roles for platelets in biological areas distinct from hemostasis are also emerging. Platelet utilization is variably affected by all of the above factors, by demographic changes, by new medications, and by new patient care approaches.
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Plaquetas/microbiología , Plaquetas/virología , Transfusión de Plaquetas/métodos , Infecciones Bacterianas/prevención & control , Bancos de Sangre , Plaquetas/citología , Conservación de la Sangre/métodos , Transfusión Sanguínea/métodos , Canadá , Ensayos Clínicos como Asunto , Humanos , Cooperación Internacional , Liposomas/química , Sepsis/prevención & controlRESUMEN
Given the explosion of research on induced pluripotent stem (iPS) cells, it is timely to consider the various ethical, legal, and social issues engaged by this fast-moving field. Here, we review issues associated with the procurement, basic research, and clinical translation of iPS cells.
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Investigación Biomédica , Células Madre Pluripotentes Inducidas/citología , Trasplante de Células Madre , Humanos , Política Pública , Donantes de TejidosRESUMEN
BACKGROUND: MyoD is a transcription factor implicated in the regulation of adult muscle gene expression. Distinguishing the expression of MyoD in satellite myoblasts and muscle fibres has proved difficult in vivo leading to controversy over the significance of MyoD expression within adult innervated muscle fibres. Here we employ the MD6.0-lacZ transgenic mouse, in which the 6 kb proximal enhancer/promoter (DRR/PRR) of MyoD drives lacZ, to show that MyoD is present and transcriptionally active in many adult muscle fibres. RESULTS: In culture, MD6.0-lacZ expresses in myotubes but not myogenic cells, unlike endogenous MyoD. Reporter expression in vivo is in muscle fibre nuclei and is reduced in MyoD null mice. The MD6.0-lacZ reporter is down-regulated both in adult muscle fibres by denervation or muscle disuse and in cultured myotubes by inhibition of activity. Activity induces and represses MyoD through the DRR and PRR, respectively. During the postnatal period, accumulation of beta-galactosidase correlates with maturation of innervation. Strikingly, endogenous MyoD expression is up-regulated in fibres by complete denervation, arguing for a separate activity-dependent suppression of MyoD requiring regulatory elements outside the DRR/PRR. CONCLUSION: The data show that MyoD regulation is more complex than previously supposed. Two factors, MyoD protein itself and fibre activity are required for essentially all expression of the 6 kb proximal enhancer/promoter (DRR/PRR) of MyoD in adult fibres. We propose that modulation of MyoD positive feedback by electrical activity determines the set point of MyoD expression in innervated fibres through the DRR/PRR element.
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Elementos de Facilitación Genéticos/genética , Regulación del Desarrollo de la Expresión Génica , Fibras Musculares Esqueléticas/metabolismo , Proteína MioD/genética , Regiones Promotoras Genéticas/genética , Animales , Células Cultivadas , Regulación hacia Abajo , Estimulación Eléctrica , Operón Lac , Ratones , Ratones Transgénicos , Desnervación MuscularRESUMEN
We assessed viable Pax7(-/-) mice in 129Sv/J background and observed reduced growth and marked muscle wasting together with a complete absence of functional satellite cells. Acute injury resulted in an extreme deficit in muscle regeneration. However, a small number of regenerated myofibers were detected, suggesting the presence of residual myogenic cells in Pax7-deficient muscle. Rare Pax3(+)/MyoD+ myoblasts were recovered from Pax7(-/-) muscle homogenates and cultures of myofiber bundles but not from single myofibers free of interstitial tissues. Finally, we identified Pax3+ cells in the muscle interstitial environment and demonstrated that they coexpressed MyoD during regeneration. Sublaminar satellite cells in hind limb muscle did not express detectable levels of Pax3 protein or messenger RNA. Therefore, we conclude that interstitial Pax3+ cells represent a novel myogenic population that is distinct from the sublaminar satellite cell lineage and that Pax7 is essential for the formation of functional myogenic progenitors from sublaminar satellite cells.
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Desarrollo de Músculos/fisiología , Músculo Esquelético/fisiología , Factor de Transcripción PAX7/fisiología , Factores de Transcripción Paired Box/fisiología , Regeneración/fisiología , Animales , Células Cultivadas , Ratones , Ratones Noqueados , Músculo Esquelético/citología , Músculo Esquelético/lesiones , Proteína MioD/metabolismo , Factor de Transcripción PAX3 , Factor de Transcripción PAX7/genética , Células Satélite del Músculo Esquelético/citologíaRESUMEN
Under normal circumstances, mammalian adult skeletal muscle is a stable tissue with very little turnover of nuclei. However, upon injury, skeletal muscle has the remarkable ability to initiate a rapid and extensive repair process preventing the loss of muscle mass. Skeletal muscle repair is a highly synchronized process involving the activation of various cellular responses. The initial phase of muscle repair is characterized by necrosis of the damaged tissue and activation of an inflammatory response. This phase is rapidly followed by activation of myogenic cells to proliferate, differentiate, and fuse leading to new myofiber formation and reconstitution of a functional contractile apparatus. Activation of adult muscle satellite cells is a key element in this process. Muscle satellite cell activation resembles embryonic myogenesis in several ways including the de novo induction of the myogenic regulatory factors. Signaling factors released during the regenerating process have been identified, but their functions remain to be fully defined. In addition, recent evidence supports the possible contribution of adult stem cells in the muscle regeneration process. In particular, bone marrow-derived and muscle-derived stem cells contribute to new myofiber formation and to the satellite cell pool after injury.
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Músculo Esquelético/fisiología , Regeneración/fisiología , Animales , Diferenciación Celular , Sustancias de Crecimiento/fisiología , Humanos , Desarrollo de Músculos/fisiología , Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/fisiología , Transducción de Señal , Células Madre/fisiologíaRESUMEN
In this issue of Cell, G. Pavlath and coworkers demonstrate a novel role for Interleukin-4 (IL-4) in regulating the fusion of myoblasts with differentiated myotubes. The authors demonstrate that NFATc2 signaling in newly formed myotubes induces IL-4 expression and secretion which promotes myoblast fusion with pre-existing myotubes.
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Diferenciación Celular/fisiología , Interleucina-4/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Mioblastos Esqueléticos/metabolismo , Animales , Fusión Celular , Humanos , Hipertrofia/metabolismo , Fibras Musculares Esqueléticas/citología , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Mioblastos Esqueléticos/citología , Transducción de Señal/fisiologíaRESUMEN
To investigate the cause of skeletal muscle weakening during aging we examined the sequence of cellular changes in murine muscles. Satellite cells isolated from single muscle fibers terminally differentiate progressively less well with increasing age of donor. This change is detected before decline in satellite cell numbers and all histological changes examined here. In MSVski transgenic mice, which show type IIb fiber hypertrophy, initial muscle weakness is followed by muscle degeneration in the first year of life. This degeneration is accompanied by a spectrum of changes typical of normal muscle aging and a more marked decline in satellite cell differentiation efficiency. On a myoD-null genetic background, in which satellite cell differentiation is defective, the MSVski muscle phenotype is aggravated. This suggests that, on a wild-type genetic background, satellite cells are capable of repairing MSVski fibers and preserving muscle integrity in early life. We propose that decline in myogenic cell differentiation efficiency is an early event in aging-related loss of muscle function, both in normal aging and in some late-onset muscle degenerative conditions.