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The Journal of Clinical Investigation Jan 2018Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have... (Review)
Review
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.
Topics: Animals; Dermis; Epigenesis, Genetic; Fibroblasts; Gene Expression Regulation, Neoplastic; Humans; Skin Neoplasms; Transcription, Genetic
PubMed: 29293096
DOI: 10.1172/JCI93555 -
Seminars in Plastic Surgery Nov 2022Despite being relatively uncommon in the general population, thumb amputations cause severe disability. More than 3,300 thumb amputations occurred in the United States.... (Review)
Review
Despite being relatively uncommon in the general population, thumb amputations cause severe disability. More than 3,300 thumb amputations occurred in the United States. The thumb makes up around 40% of the function of the hand. Therefore, losing it would result in significant medical, hospital, and societal costs. Thumb reconstruction surgery's primary goal is to restore grip strength, including the range of motion, fine and tripod pinch, power grasp, strength, and sensibility, while secondary goals include restoring hand aesthetics. In cases of thumb replantation, like-for-like replacement is possible; however, when thumb replantation is not possible, great toe-to-hand transplantation is the best available reconstruction. When compared with other reconstructive options such as osteoplastic thumb reconstruction, pollicization, second toe transplantation, and the use of a thumb prosthesis, great toe transplantation provides superior function and aesthetics. For restoring pinch, sensitivity, strength, and aesthetics of the hand with well-tolerated donor site morbidity, toe to thumb transplantation is regarded as the gold standard.
PubMed: 36561428
DOI: 10.1055/s-0042-1758689 -
Seminars in Plastic Surgery Nov 2022Phalloplasty in the female to male transgender patient is a complex operation aimed at creating a functional and aesthetic phallus, external genitalia, and perineum.... (Review)
Review
Phalloplasty in the female to male transgender patient is a complex operation aimed at creating a functional and aesthetic phallus, external genitalia, and perineum. Functional goals include standing micturition and sexual function with erogenous and tactile sensation as well as the ability to participate in penetrative intercourse. Functional genital reconstruction relies on creating of a fully lengthened urethra from local tissues as well as the provision for additional length via tissue transplantation. This manuscript will review techniques for the creation of perineal urethral segment as well as primary flaps available for the creation of neophallus. Particular emphasis is given to our preferred method of reconstruction: single-stage urethral lengthening with radial forearm flap phalloplasty including a review of surgical techniques and complications.
PubMed: 36561429
DOI: 10.1055/s-0042-1758226 -
CMAJ : Canadian Medical Association... Nov 2021
Topics: Alzheimer Disease; Antibodies, Monoclonal, Humanized; Canada; Drug Approval; Drug Costs; Humans; Immunologic Factors; Infusions, Intravenous; Randomized Controlled Trials as Topic; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 34725122
DOI: 10.1503/cmaj.211134-f -
Osteoarthritis and Cartilage Mar 2018To summarise important findings from biomarker studies relevant to osteoarthritis (OA), published between April 2016 and March 2017; to consider these findings in the... (Review)
Review
OBJECTIVE
To summarise important findings from biomarker studies relevant to osteoarthritis (OA), published between April 2016 and March 2017; to consider these findings in the context of new discoveries and technologies, and clinical and scientific need in OA.
DESIGN
Studies were selected by PubMed search, conducted between 01/04/2016 and 01/03/2017. MeSH terms [biomarker] AND [OA] were used; the search was restricted to Human, English language and Full Text Available publications, which yielded 50 eligible publications. Any biomarker was considered, including non-proteins and other clinical measurements.
RESULTS
Three main areas are overviewed: 1) Studies examining highly validated biomarkers, in the FNIH OA Biomarkers Consortium and elsewhere, particularly their ongoing application and validation. Control reference intervals, work on predictive validity and other longitudinal studies examining prognostic value of biomarkers in large cohorts are reviewed. 2) Novel studies relating to biomarkers of inflammation are discussed, including complement, the performance of markers of so-called 'cold inflammation' and results from clinical trials including biomarkers. 3) Discovery studies, including whole blood RNA, proteomics and metabolomics are reviewed, with an emphasis on new technologies.
CONCLUSIONS
Discovery, characterisation and qualification of various biomarkers is ongoing; several novel protein and non-protein candidate biomarkers have been reported this year. Biomarkers provide us with an opportunity to better diagnose and stratify the disease, via established panels or new discovery approaches. Improving quality of sampling and testing, and measuring large numbers of markers simultaneously in large cohorts would seem likely to identify new clinically applicable biomarkers, which are still much needed in this disease.
Topics: Biomarkers; Humans; Osteoarthritis; Prognosis; Treatment Outcome
PubMed: 29107060
DOI: 10.1016/j.joca.2017.10.016 -
Frontiers in Psychology 2019
PubMed: 31798493
DOI: 10.3389/fpsyg.2019.02514 -
Cold Spring Harbor Perspectives in... Jun 2022Fibroblasts are the main cell type in the dermis. They are responsible for the synthesis and deposition of structural proteins such as collagen and elastin, which are...
Fibroblasts are the main cell type in the dermis. They are responsible for the synthesis and deposition of structural proteins such as collagen and elastin, which are integrated into the extracellular matrix (ECM). Mouse and human studies using flow cytometry, cell culture, skin reconstitution, and lineage tracing experiments have shown the existence of different subpopulations of fibroblasts, including papillary fibroblasts, reticular fibroblasts, and fibroblasts comprising the dermal papilla at the base of the hair follicle. In recent years, the technological advances in single-cell sequencing have allowed researchers to study the repertoire of cells present in full-thickness skin including the dermis. Multiple groups have confirmed that distinct fibroblast populations can be identified in mouse and human dermis on the basis of differences in the transcriptional profile. Here, we discuss the current state of knowledge regarding dermal fibroblast heterogeneity in healthy mouse and human skin, highlighting the similarities and differences between mouse and human fibroblast subpopulations. We also discuss how fibroblast heterogeneity may provide insights into physiological wound healing and its dysfunction in pathological states such as hypertrophic and keloid scars.
PubMed: 35667795
DOI: 10.1101/cshperspect.a041238 -
CMAJ : Canadian Medical Association... Jan 2024
Topics: Humans; Alzheimer Disease; Canada; Antibodies, Monoclonal, Humanized
PubMed: 38286492
DOI: 10.1503/cmaj.230595-f